Graduate Student & Post-Doctoral Scholar Poster Session
March 26, 2024
March 26, 2024
Date: March 26th, 2024
Time: 12:00 pm to 3:30 pm
Venue: Rowan University
Theme: Sustainability
Slogan: "A 100-year foundation supporting research on solving today's problems for a sustainable future!"
12:00 pm - 12:30 pm: Welcome and Kick-off
12:30 pm - 1:00 pm: Keynote Address
1:00 pm - 3:00 pm: Poster Symposium
3:00 pm - 3:30 pm: Poster Prizes and Closing
4:00 pm Beer Reception in Student Center
First Name Last Name Area of Responsibility
Omar Al-Odat Evaluation and Feedback
Christina Newlands Evaluation and Feedback
Shaileen Woods Logistics
Nicholas Paradis Program and Schedule
Elias Elias Program and Schedule
Rachel Young Publicity and Print Materials
Anudeep Deevi Refreshments
Matthew Pekora Sponsorship and Fundraising
Find Your Poster Number (sorted by last name):
Poster # First name Last name
83 Antonio Abbondandolo
24 Nadia Afrin
46 Okikiola Agbabiaka
45 SHAKIL AHMED
38 Mohammad Alkhatib
73 Fayez Alruwaili
60 Shaini Aluthgun Hewage
75 Morgan Antisell
26 Daniel Arango-cardona
99 Jose de Jesus Argueta Donohue
16 Priya Aryal
58 Anil Kumar Baditha
62 Anil Kumar Baditha
3 Jennifer Balbuena
92 Daniel Ball
9 Shrhea Banerjee
15 Katie Beck-Felts
2 Madeline Boehning
50 Taha Bouhsine
51 Giuseppina Carannante
61 Mohit Chaudhary
30 Jamie Clapp
39 Kevin Daus
25 Lilliana De Salas
76 Navya Sree Devaguptapu
94 Oyku Dinckol Perni
55 Leeza Duller
87 Shahab Edalatian Zakeri
14 Elias Elias
48 Atik Faysal
67 Brittany Friedson
34 Julia Gabriel
1 Allison Gainer
78 Narangerel Gantumur
54 Barnabas Gao
52 Arunkumar Goli
66 Liza Guner
5 Rachel Hill-Pizzo
40 Robyn Himelstein
93 Nicole Hinds
85 Samuel Hofbauer
91 Evan Hutt
68 Jibran Imtiaz
21 Khushi Jain
84 Umu Jalloh
98 Benjamin Jelen
59 Ibrahim Joel
100 Pavan Goud Juluri
63 Mohamad Keblawi
74 James Kennedy
96 Mahdie Kerdari
97 Mahdie Kerdrai
77 Emily Kopchick
47 Adarsh Kumar
28 Adriann Lai
53 Gali Lakshamana Raj
57 Austin Lehr
88 Enosh Lim
70 Stacy Love
6 Kayla Maharaj
37 Sravani Malasani
43 Sravani Malasani
18 Janine Mazahreh
41 Erin McKenney
44 Pintu Miah
36 Rosalind Moore
11 Rohit Nambiar
65 Quy Nguyen
17 Alexandra Nicoletti
64 Cristina Padovani
10 Nicholas Paradis
29 Alicia Petrany
42 Khanh Pham
72 Vanessa Pizutelli
80 Haven Predale
86 Matthias Recktenwald
69 Tamaraty Robinson
49 Mohammad Rostami
90 Dipon Roy
27 Gabrielle Salvatore
8 Hadarou Sare
19 Faith Shank
4 Danelle Sheply
89 Myranda Sims
20 Cody Soper
13 Lauren Staman
7 Colin Stiles
35 Bamidele Towolawi
33 Annie Tran
81 Camila Vardar
31 Kasmier Vicioso
12 Autumn Vossler
79 Erin Wannen
23 Nakoa Webber
95 Noah Wenger
56 Garrett Williams
71 Victoria Wong Murray
82 Rachel Young
22 Jacob Zangaro
32 Ariel Zhang
1. Allison Gainer
Ed.D in Educational Leadership
Advisor: N/A
Title: Exploring the Influence of Higher Education on Perceptions and Knowledge Gaps Regarding Service Dogs
Abstract: Exploring the perceptions and knowledge gaps within college communities regarding service dogs and their handlers can unveil barriers in higher education. By critically examining social and cultural factors contributing to challenges faced by individuals with service dogs in academic settings, we can shed light on the responsibility and influence of higher education institutions in shaping societal attitudes towards disability and inclusion. This research aims to shape political attitudes and public policies surrounding accessibility and accommodation in higher education.
2. Madeline Boehning
PhD in Education
Advisor: Shelley Zion
Title: An exploration of NJ’s identity-based curriculum policies within school climate transformation RPP work
Abstract: As some states face a backlash against equitable and inclusive curriculum reform efforts, other states have successfully passed legislation backing this type of reform. This mixed-methods study explores how schools respond to state identity-based curriculum laws requiring the inclusion of the history and contribution of underrepresented groups. Three districts engaged in a school climate transformation research practice partnership participated. Data collection included school leader interviews, teacher focus groups, content analysis, and school climate survey data. The research revealed four themes: a) awareness and support, b) connections to school climate work, c) lack of time/resources for meaningful implementation, d) disparate attention to specific laws. This study may guide state policy actors interested in creating identity-based curriculum laws and for schools focused on deeper implementation.
3. Jennifer Balbuena
MA in Higher Education
Advisor: N/A
Title: ROWAN UNIVERSITY CHAMP/GEAR UP PROGRAM PROPOSAL: A DAY IN THE LIFE OF A COLLEGE STUDENT
Abstract: The Rowan University CHAMP/ GEAR UP Program has positively impacted students throughout generations and GEAR UP’s impact throughout the nation. The new initiative at Rowan University's CHAMP/ GEAR UP program, “A Day in the Life of a College Student”, will take current CHAMP students out of their daily routine in high school and follow a current CHAMP mentor for a day. Students participating will learn a new perspective on what it’s like to be a college student at Rowan University. “A Day in the Life of a College Student” is a testament to student development theory and Tinto’s theory.
4. Danelle Sheply
EdS in School Psychology
Collaborators: Tijani Bullock, Emily Hinlicky
Advisor: Carmelo Callueng
Title: Enriching Multicultural Competence of School Psychology Trainees
Abstract: The increasing diversity of children and youth in schools necessitates school psychology trainees to develop high level multicultural competence to effectively provide culturally relevant and equitable support services to address students’ needs. This longitudinal study explored the impact of graduate training in multicultural competence of EdS school psychology students. It was predicted that field experience of school psychology students will significantly strengthen their multicultural competence. Results of the three waves of assessment using School Psychology Multicultural Competence Scale indicated that field experience greatly contributed in improving the multicultural competence of students compared to the impact of classroom-based coursework. In conclusion, school psychology students benefit from both didactic coursework that explicitly teaches multicultural competency in service delivery as well as rich field experience that allows them to practice these skills learned in course work. Implications and limitations of the study will be discussed.
5. Rachel Hill-Pizzo
Ed. S. School Psychology
Collaborators: Rachel Pizzo, Nicole Dudek, Aiyahna McCoy
Advisor: Carmelo Callueng
Title: Universal Mental Health Screening in a High-Need School District
Abstract: This study examined the behavioral and social-emotional risks as well as the adaptive strengths of students in a highly diverse suburban school district. It also determined possible variations in risks and strengths as accounted by students’ gender, grade level, and race/ethnicity. Finally, the study explored the underlying mental health profiles of students using the BIMAS-2 scales as indicators. As a secondary aim, confirmatory factor analysis (CFA) was conducted to assess the construct validity of the BIMAS-2.
6. Kayla Maharaj
MA in History
Advisor: Emily Blanck
Title: Early Representation of Black Students in The Whit at Rowan University: a Digital Collection
Abstract: Early representation of Black Students In The Whit at Rowan University is a digital collection created by Kayla Maharaj and includes articles published between 1939 and 1969. The Whit is a college newspaper created in 1938 and is still being published today at Rowan University. The college was founded in 1923 as the Glassboro Normal School–a teacher's college. This project came to be after looking through dozens of old college newspapers found in the Rowan University Archive and Special Collections that connected to the Civil Rights Movement in the United States. This collection is made up of 72 scanned newspaper articles and images relating to Black students and/or national race issues. Each document was chosen based on the following criteria: it explained racial issues on or off campus, it mentioned events that were promoted for the Black community, it was an image of Black student(s), or connected to Black students in any other way. Because of the wide range of criteria, many of the documents do not specifically relate to any other. However, each item is important to the history of the representation of black students at Rowan University. Each article or image in the collection has been included along with a full scan on the page that it was published on in The Whit. The project has its own site (https://omeka.rowandsc.org/s/representation-in-the-whit/page/home) where viewers can look through these scanned documents.
7. Colin Stiles
MA in History, Certificate of Graduate Study in Holocaust & Genocide Education
Collaborators: Elizabeth Rantuccio
Advisor: Jody Russel Manning
Title: Gender Matters
Abstract: Within each process of genocide, there is a penchant for targeting groups that cannot resist the oppression laid upon them. As such, the role of gender in the perpetration, experience and aftermath of these processes is vastly overlooked. This project looks over three major case studies to better understand gender within the process of genocide; China, Myanmar and Rwanda. Using the lenses of gender studies, sociology and history, we seek to understand the methodology behind gendercide as well as the social, malicious and religious motivations behind it. Within China, we look at the Uyghur population, a culturally Muslim minority which has been targeted since 2014, and has had numerous cases of women being sterilized in order to prevent the culture of the Uyghur people from spreading. In Myanmar is a similar case, the culturally Muslim Rohingya people have been targeted for their Hijra group, which consists of trans individuals. The genocide in Myanmar also targets the boys and men of the Rohingya, mutilating their genitalia, forcing themselves upon their partners or assaulting them outright. Within the Rwandan genocide, women were targeted as subjects of sexual assault, with approximately 49% of the women experiencing rape at the hands of the perpetrators. Using these instances, this project seeks to answer the question “Does gender matter?” within the context of genocide studies. Using these metrics, we explore the roles of gender and cross reference them with numerous genocidal processes in which they were present to determine the answer. In looking into the roles that gender plays within genocide, we can better understand our approach to the matter while not only bolstering our ability to address it in the future, but possibly preventing it outright.
8. Hadarou Sare
PhD in MSE
Advisor: Dongmei Dong
Title: Modeling, Simulation, and Experimental Testing of a High Strength and High-Temperature Resistant Composite Structure Material for In-Space Optical Mining Application
Abstract: The study delves into modeling, simulations, and experimental testing of a composite material tailored for high-strength and high-temperature resistance, specifically for in-space optical mining. It encompasses mechanical performance analysis, thermal property evaluation, and material testing, using COMSOL for structural modeling and simulation. Mechanical investigation employs three methods for composite structure modeling: Layerwise theory, Equivalent Single Layer (ESL) theory, and a multiple model method. Modal and frequency-response analyses compare their performance in assessing through-thickness stress distribution. Thermal investigation in COMSOL simulates heating by a radially moving laser, analyzing transient thermal response. Peak, average, and minimum temperatures during heating, along with temperature variations across the material, are computed. Experimental investigation utilizes electrochemical polymerization to create a porous PANI film layer. Electrodeposition parameters yield optimal film quality, with a comprehensive study on surface morphology, performance, electrochemical behavior, and molecular structure evolution. Linear colorimetric behavior and significant changes in Raman spectra establish quantitative relations in EC polymers. Well-defined oxidation and reduction peaks in cyclic voltammetry indicate an ion-diffusion dominant process in PANI electrochromism, with transitions between benzene and quinone phases in Raman spectra observed. Contributions include novel material development for in-space optical mining, integration with mining systems, and thermal management solutions. Understanding material behavior in space environments, evaluation of resource efficiency and sustainability, interdisciplinary collaboration, and contribution to future space exploration are emphasized. Insights into PANI film structure and properties enhance understanding of dual-function EC charge storage polymers. This work's findings are pertinent for in-space optical mining endeavors.
9. Shrhea Banerjee
PhD in Pharmaceutical Chemistry
Advisor: Zhihong Wang
Title: Targeting Protein-Protein Interactions within the MAPK Pathway for Cancer Therapy
Abstract: The Mitogen Activated Protein Kinase (MAPK) cascade, comprising RAS, RAF, MEK, and ERK, regulates essential cellular functions like cell proliferation and survival. Notably, mutations in RAF kinase and RAS proteins often hyperactivate this pathway, a common occurrence in various human cancers. We conduct comprehensive biophysical and biochemical characterization of Braftide, a peptide developed in our lab to allosterically target the RAF dimer interface. Our findings suggest that Braftide also holds promise in targeting RAF signaling by disrupting the CDC37-RAF kinase interface, presenting a novel proof-of-concept strategy. This approach offers a route to intervene in the molecular chaperone network involving Heat Shock Protein 90 (HSP90) and its co-chaperone, CDC37, both regulators pivotal in kinase-specific protein folding, stabilization, and activity. In alignment with our research focus, we also study the interaction between RAS and RAF proteins. This interaction triggers significant conformational changes in RAF, however, the specific order and mechanistic details of these interactions remain elusive. Critical to this process are the interplays among RAF regulatory domains (RAS Binding Domain (RBD), Cystine Rich Domain (CRD), Kinase Domain (KD)), governing the interaction with RAS and the consequential conformational shifts that drive RAF activation. Our research aims to elucidate these key details using in vitro biophysical methods such as Open Surface Plasmon Resonance (OpenSPR) and deuterium exchange mass spectrometry (HDX). We study the RAS-RAF interactions by accessing alterations in binding affinities and conformations within the regulatory domains upon exposure to different RAS isoforms (HRAS, KRAS, and NRAS), along with pan-RAS inhibitors currently under clinical development. Collectively, our efforts enhance understanding of the biochemical mechanisms governing RAF activation and regulation. Furthermore, our exploration of innovative approaches for targeting RAF and RAS mutations holds promise for advancing therapeutic interventions in these malignancies.
10. Nicholas Paradis
PhD in Pharmaceutical Chemistry
Advisor: Chun Wu
Title: Near-Neutral Balanced Selection Theory (NNBST): Implication on the molecular evolution of SARS-CoV-2 and Zika virus
Abstract: Virus pandemics have significantly impacted human welfare and development. Understanding the true molecular evolution of viruses is critical for preventing future pandemics and developing the next-generation drugs and vaccines. Unfortunately, viruses exhibiting constant genomic substitution rates (GSRs) despite increasing vaccinations and human infections (SARS-CoV-2) and viruses under seemingly extreme conservation (ZIKV) paints a confusing picture of viral evolution, and the main evolutionary theories (Selectionist Theory, Kimura’s Neutral Theory) cannot explain their molecular evolution. Here, we developed a first-principle model, c/u, to characterize reproductive fitness changes in viruses based on variations in the nucleotide/codon mutation rate (c) with respect to the global genomic mutation rate (u). c/u is nucleotide-centric, since phenotypic changes in proteins are reflected by genotypic changes in genes. c/u can assign selection types to coding regions (virus function) and non-coding untranslated regions (UTRs, virus gene regulation). Additionally, c/u can handle conserved sites (c/u=0) and sites with few mutations under false positive selection (c/u<<<1, Ka/Ks >>>1). The constant GSRs of SARS-CoV-2 and ZIKV are seemingly under effective neutral selection (c/u=1), indicating no advantageous/disadvantageous fitness change. Yet, the L-shaped probability distribution of c/u for a NT site indicates high sequence conservation, with higher c/u values being increasingly uncommon. Varying nucleotide and segment substitution rates were observed in both viruses, indicating a mixture of advantageous selection (c/u>1) and purifying selection (c/u<1). The higher and lower substitution rates of each segment (c) likely balance each other to generate the constant GSR (u) consistent with our Near-Neutral Balanced Selection evolution Theory (NNBST). Applications of NNBST include 1) surveillance of hotspot mutations which promote drug/antibody resistance and optimize virus activity; 2) identifying novel sites as antigens for vaccine development.
11. Rohit Nambiar
MS in Pharmaceutical Sciences
Collaborators: Pintu Miah
Advisor: Thomas Keck
Title: Evaluating the Analgesic Effects of DS-II-48 and CP-55,940
Abstract: Opioids are effective analgesics, but have undesirable side effects including constipation, abuse liability, respiratory depression, and overdose deaths. Cannabinoids have been explored as an alternative analgesic strategy but have their own undesirable side effects including constipation, respiratory depression, and loss of consciousness. Previously we have reported that α2/α3-selective GABA A positive allosteric modulators like DS-II-48 (an HCl salt of MP-III-024) can synergistically enhance opioid analgesia without increasing opioid side effects, effectively widening the therapeutic window for opioid analgesia. This project is focused on determining whether DS-II-48 can similarly synergize with the antinociceptive effects of the synthetic cannabinoid receptor 1 (CB-1) agonist CP-55,940. Herein we report that while both male and female mice have similar responses to DS-II-48 in the hot plate assay, there were substantial sex differences in response to CP-55,940. In follow-up studies using only male mice, DS-II-48 and CP-55,940 elicited dose-dependent antinociceptive effects to mechanical stimuli in the von Frey assay. Ongoing tests are evaluating the effects of concurrent administration of both DS-II-48 and CP-55,940 in males and females. These results will help us determine if simultaneous targeting of CB1 and α2/α3 GABA A receptors is a viable route towards improved analgesia. Discovering new analgesic treatment regimens will hopefully improve the quality of living for patients undergoing pain treatment.
12. Autumn Vossler
PhD in Pharmaceutical Chemistry
Advisor: Rashanique Quarrels
Title: Synthesis and Derivatization of Vancomycin Linear Heptapeptide
Abstract: Vancomycin is a last resort antibiotic that is used to treat bacterial infections in the colon and in the intestines. Currently, antibiotic resistance is a public health crisis that results in changes to how bacteria respond to antibiotic treatment. The goal of this project is to address this issue by designing new glycopeptides through peptide coupling and Umpolung Amide synthesis. Herein, we report our progress towards the synthesis of the Vancomycin heptapeptide and intermediates towards Vancomycin derivatives.
13. Lauren Staman
MS in Pharmaceutical Sciences
Collaborators: Julianna Alimenti
Advisor: Ben Carone
Title: Exploring the Role of CTCF in Gene Regulation and Chromatin Architecture Through Model shRNA Knockdown System
Abstract: Chromatin architecture has been shown to be important for the establishment and maintenance of transcriptional patterning during cell differentiation and development. One of the major players in establishing higher-order chromatin structure is CCCTC-binding factor (CTCF), a ubiquitously expressed and highly conserved gene found extensively across eukaryotic organisms¹. This gene has specifically been noted for its intrinsic roles in genomic imprinting, topological domain organization, and DNA loop structuring. When mutated, repressed, or knocked out, CTCF is embryonic lethal and thus, it has been classically challenging to study the role of this critical epigenetic regulator in transcriptional programming. Work here describes the optimization of an inducible knockdown model in mammalian cells using Short Hairpin RNAs (shRNAs). Ongoing studies focus on determining how shRNAs are capable of silencing the expression of CTCF via RNA interference.
14. Elias Elias
PhD in Complex Biological Systems
Advisor: Melissa Manners
Title: Voluntary Wheel Running Promotes Resilience to the Behavioral Effects of Unpredictable Chronic Mild Stress in Male and Female Mice
Abstract: Besides significant benefits to physical health, exercise promotes mental health, reduces symptoms of mental illness, and enhances psychological development. The effects of exercise on chronic stress-induced behaviors are contradictory in preclinical studies, primarily due to the lack of data and sex-specific investigations. We sought to evaluate the effects of exercise on chronic stress-induced behavioral changes in both male and female mice. Mice were subjected to an Unpredictable Chronic Mild Stress (UCMS) paradigm with accessibility to running wheels for 2 h daily. Chronic stress induced voluntary wheel running (VWR) and weight loss in mice. Compared to males, increased VWR was reported in females who also regained their weight lost by the end of the UCMS protocol. Exercise promoted resilience to stress-induced hyponeophagia and increased sucrose consumption. Exercise induced a sex-specific reduction in immobility and avoidance behavior and increased exploratory behavior in the light-dark test. These results indicate that exercise can promote resilience to the behavioral effects of chronic stress in males and females and can affect behavior independent of chronic stress.
15. Katie Beck-Felts
PhD in Clinical Psychology
Advisor: Tom Dinzeo
Title: A Social Ecology Model for Social Determinants of Health as Psychosis Risk Factors
Abstract: Introduction: Psychosis is a complex syndrome marked by positive symptoms like delusions and hallucinations, often accompanied by comorbidities. Early identification of at-risk mental states is crucial. Schizotypy, traits resembling schizophrenia symptoms, aids in predicting psychosis. Genetic factors alone explain limited variance in psychosis risk, emphasizing the role of social and environmental factors. Social determinants of health (SDOHs), including economic stability and social relationships, significantly impact psychosis risk. Recognizing these influences is essential for effective preventive measures. This study examines SDOHs using a CDC-developed four-level model, aligning with Bronfenbrenner's social ecology theory, providing a comprehensive framework for understanding and intervening in psychosis risk. Methods: College students (N = 213) at a large midwestern university completed a series of self-report measures assessing childhood trauma, minority group position, migration status, social connectedness, urbanicity, cannabis and alcohol use, health care access, and variables used to determine SES (parental income, parental education level) via online surveys. Results: Analyses will be conducted closer to the date of the conference. Discussion: Understanding SDOH risk factors is critical in identifying individuals at higher risk of developing psychosis-spectrum disorders in order to intervene before symptom onset. Additionally, many of these SDOHs, such as social connectedness, present novel targets for interventions in individuals with increased risk.
16. Priya Aryal
PhD in Complex Biological System
Advisor: Jason Heindl
Title: A cell cycle dependent dual function diguanylate cyclase/phosphodiesterase, regulates motility and attachment in Agrobacterium tumefaciens
Abstract: Cyclic diguanylate monophosphate (c-di-GMP) is a second messenger that is responsible for attachment and biofilm formation and controls the signaling pathway for motile to sessile transition in many bacteria. Many c-di-GMP-metabolizing proteins are diguanylate cyclases (DGCs), responsible for the synthesis of c-di-GMP and characterized by GGDEF domain. Other c-di-GMP-metabolizing proteins contain c-di-GMP degradative domains e.g., EAL, characterized by phosphodiesterase activity (PDE). This project focuses on the predicted dual function DGC/PDE metabolizing protein in Agrobacterium tumefaciens, Atu3207. We hypothesized that Atu3207 plays a role in the overall metabolism of c-di-GMP affecting biofilm formation and motility. We cloned Atu3207 into a broad host range plasmid and constructed a deletion strain lacking Atu3207 (ΔAtu3207). We then performed a biofilm and motility assays to determine the effect of Atu3207 on these important developmental phenotypes. Our results show that the ectopic expression of Atu3207 in the wild-type (WT) C58 strain of A. tumefaciens has a significant reduction in biofilm formation and increased motility when compared to empty vector controls. Moreover, ΔAtu3207 showed a reciprocal result. Atu3207 was able to complement both phenotypes in ΔAtu3207 background. Further, we performed site-directed mutagenesis on both domains. Expression of an allele of Atu3207 carrying mutagenized GGEEF (GGAAF) domain resulted in significant biofilm reduction in WT. Conversely, expression of an allele of Atu3207 carrying a mutagenized EAL (AAL) domain resulted in a significant increase in biofilm formation in WT. Using a beta-galactosidase transcriptional reporter for the activity of the Atu3207 promoter, we show cell cycle-dependent expression. We tagged Atu3207 with GFP to study the localization of the protein. Atu3207-GFP showed polar localization using epifluorescence microscopy. Overall, our results suggest that Atu3207 affects c-di-GMP metabolism, resulting in cell cycle-dependent control of motility and biofilm formation in A. tumefaciens, most likely functioning as a cell cycle-dependent PDE under our experimental conditions.
17. Alexandra Nicoletti
PhD in Clinical Psychology
Advisor: DJ Angelone & Meredith Jones
Title: “He came on too strong”: Women’s perception of sexual risk in an online speed-dating paradigm
Abstract: Previous research has evaluated women’s tolerance of sexual harassment with the use of vignette scenarios (Pumphrey-Gordon & Gross, 2007; Norris et al., 2006), though these studies do not mimic real-world experiences. Recently, researchers have utilized laboratory analogues to examine women’s sexual risk recognition and tolerance of sexual harassment in an online speed-dating format with bogus male dating candidates (EduDate; Angelone et al., 2009). The current study extended upon this paradigm work and assessed women’s qualitative responses about their sexual violence risk recognition. Participants were single, female, social drinkers, who engaged in the EduDate paradigm as part of a larger study about alcohol intoxication and sexual violence risk perception. During the speed date, women interacted with a bogus dating candidate who responded to questions in a manner predetermined to be either a low or high risk. After the speed date, women provided qualitative responses about their perceptions of the date. We used a thematic analysis to understand women’s experiences of conversing with men in an online dating format, including why they ended their date, and aspects of their date’s behavior that made them uncomfortable. Multiple themes were identified within the qualitative responses: hypersexuality in their dating partner (i.e., focusing on sex) with subthemes of objectification of women and being sexually forward. Specifically, women perceived their partner’s hypersexuality as a risk cue. Other themes included incompatibility, lack of authenticity, and general displeasure. Our findings suggest that women became uncomfortable and perceived sexual violence risk in online dating conversations when men focused the conversation around sex, particularly when it was perceived to be “too forward too soon.” Additionally, women identified displeasure and a lack of compatibility as reasons they did not continue their date. Future researchers should utilize the EduDate paradigm to assess other situational variables that impact women’s sexual violence risk perception.
18. Janine Mazahreh
PhD in Pharmaceutical Chemistry
Advisor: Nathaniel Nucci
Title: Characterizing the composition dependence of exchange rates in reverse micelle systems by stopped- flow fluorescence
Abstract: Reverse Micelles (RMs) are thermodynamically stable nanodroplets composed of a bulk organic solvent and an inner aqueous core stabilized by a surfactant layer. RMs are used in numerous applications ranging from biophysical studies of protein confinement and nanoparticle growth to large scale industrial practices such as petroleum extraction and synthetic chemistry. Due to the nanoscale size of these droplets, their movement is dominated by Brownian motion, causing the droplets to randomly collide, coalesce to exchange contents, and decoalesce continuously. Predictive application of RM systems for synthetic and analytical processes requires a thorough understanding of the complexities of intermicellar collision behaviors in relation to their compositional makeup. Here we present the characterization of RM content exchange using the formation of a highly fluorescent chelate in the aqueous pools of sodium bis(2-ethylhexyl) sulfosuccinate (AOT) RMs. The fluorescence kinetics for the reactant probe molecule terbium(III) chloride and the chelating agent, dipicolinic acid, were examined first in bulk aqueous solution and encapsulated in RMs of varying water loading, organic solvent, and surfactant headgroup pH with a goal of establishing the influence that each of these parameters has on the RM exchange rate. We demonstrate the influence that the tested conditions have on the elasticity of the surfactant layer, which is a key parameter that dictates the rate limiting step in RM exchange, Kopening. The findings presented here are intrinsic to a broad scale model that will allow for a manipulation of exchange rate by altering the composition of RMs.
19. Faith Shank
PhD in Clinical Psychology
Advisor: DJ Angelone & Meredith Jones
Title: Differences In Drinking Patterns In Graduate Students Based On Degree Type
Abstract: Graduate school is accompanied by high levels of stress, as students are faced with various responsibilities (El-Ghoroury et al., 2012; Offstein et al., 2004). However, many graduate students have barriers to mental health services, resulting in the use of maladaptive coping mechanisms, specifically alcohol use (Ayala et al., 2017). Related, professional doctoral students (e.g., MD, OD, JD) tend to engage in problematic drinking, with a range of 33-50% drinking heavily (Organ et al., 2016; Waring et al., 1984). There is limited research examining the drinking patterns of students enrolled in different types of programs. We aimed to examine differences in drinking patterns among various degree types. Participants were 227 graduate students (55% female, 72% Caucasian, 38% Latino) with a mean age of 26 (SD = 3). Recruitment was conducted through social media outlets and participants completed a one-time online assessment. Students were divided into three groups: masters (N = 92), academic doctoral (N = 113), and professional doctoral (N = 72). Two negative binomial regressions were used to examine differences in drinks per week and alcohol-related consequences. Based on Tukey’s post-hoc analyses, There were significant differences between Masters (M = 6.20) and Academic Doctoral (M = 11.92) students, and Masters (M = 6.20) and Professional Doctorate (M = 9.44) students in their drinks per week. In addition, there were significant differences between Masters (M = 6.10) and Professional Doctoral (M = 8.93) students. A generalized linear model was used to explore AUDIT score (hazardous drinking) differences. There were significant differences between Masters (M = 10.47) and Academic Professional (M = 13.52) students, and Masters (M = 10.47) and Professional Doctoral (M = 14.81) students. These results may inform future interventions for this population, suggesting a need to modify content for the different types of students.
20. Cody Soper
PhD in Material Science & Engineering
Advisor: Nicholas Whiting
Title: Comprehensive Characterization of Hydrothermally Derived 13C-Enriched Carbon Quantum Dots
Abstract: The exploration of carbon-based nanomaterials has opened new vistas in nanotechnology and materials science due to their remarkable properties and versatile applications. This study focuses on the hydrothermal synthesis of carbon quantum dots (CQDs) using 13C enriched urea and citric acid, aiming to develop a deeper understanding of their structural, optical, and chemical characteristics. The synthesis process is optimized to yield high-quality CQDs, with an emphasis on the effects of 13C enrichment on the material's properties. Comprehensive characterization techniques, including X-Ray Diffraction (XRD), Raman Spectroscopy, Nuclear Magnetic Resonance (NMR), Fluorescence Spectroscopy, UV-Vis Absorbance, Fourier Transform Infrared Spectroscopy (FTIR), and Transmission Electron Microscopy (TEM), were employed to elucidate the quantum dots' crystallinity, molecular structure, size distribution, and optical properties. Our findings reveal distinct structural features and enhanced optical behavior, attributed to the 13C enrichment and hydrothermal synthesis conditions.
21. Khushi Jain
MS in Pharmaceutical Sciences
Advisor: Chun Wu
Title: Enterovirus D68 Follows NNBST: Validating c/u as the best method for studying viral evolution
Abstract: Enterovirus D68 (EV-D68), first identified in the USA in 1962, has been associated with severe respiratory illness and acute flaccid myelitis since its 2014 outbreak. Mutations in both its Translated Region (TR) and Untranslated Region (UTR) are believed to drive sudden changes in pathogenicity and virulence. However, our understanding of EV-D68's evolution remains incomplete, making way for the Near-Neutral Balanced Selectionist Theory (NNBST). By employing c/µ analysis, which examines selection pressure at the nucleotide level, this study challenges traditional protein-centric approaches and proposes a "balanced selection" model, revolutionizing current evolutionary paradigms. This innovative strategy aims to identify conserved and variable genomic regions, facilitating the development of novel therapeutics.
22. Jacob Zangaro
Ph.D in Pharmaceutical Chemistry
Advisor: Nathaniel Nucci
Title: Probing Hydration Dynamics of Antifreeze Protein M1.1 by NMR Spectroscopy
Abstract: Hydration dynamics are important for the folding and function of proteins. Solvation and desolvation of local regions of protein surfaces modulate protein-protein and protein-drug thermodynamics. NMR measurement of hydration dynamics in bulk aqueous solution is complicated by multiple factors including the rapid mobility of bulk water and contamination of measurements by hydrogen exchange-mediated artifacts. Encapsulation of proteins in the nanoscale interior of reverse micelles has been shown to largely overcome these challenges and facilitate comprehensive measurement of water mobility across the protein surface. Reverse micelles (RMs) are spontaneously organizing complexes composed of surfactant, water, and bulk organic solvent. Under optimized conditions, RMs allow for encapsulation of proteins with maintenance of the native fold. Here, we use RMs to measure the dynamics of water across the surface of the antifreeze protein M1.1, a mutated form of the type-III ice-binding protein from ocean pout. Antifreeze proteins present an intriguing case for study of water in the process of molecular recognition, as their binding target is frozen water in a background of liquid water. We present measurements of water mobility across the M1.1 surface at multiple temperatures, thereby gaining insight into the functional hydration of this protein.
23. Nakoa Webber
PhD in Complex Biological Systems
Advisor: Nathaniel Nucci
Title: Effects of Confinement and Interfacial interactions on Flavodoxin Stability
Abstract: The vast majority of thermodynamic studies of protein stability have been performed in dilute aqueous solution. The environment within the cell presents restricted space and non-specific interfacial interactions. Here, we use reverse micelles to better understand the interplay between stabilizing effects such as confinement and interactions expected to destabilize proteins such as weak, non-specific interfacial binding. Reverse micelles are spontaneously organizing complexes composed of surfactants enclosing a nanoscale water pool dissolved in a nonpolar solvent. Surfactants including decylmonoacyl glycerol (10MAG) and lauryldimethylamino-N-oxide (LDAO) or cetyltrimethylammonium bromide (CTAB) with hexanol have been proven to effectively encapsulate proteins in confined environments while preserving their native conformations. Encapsulation of flavodoxin, an electron-transfer protein, is used as the model protein for these thermodynamic studies measured by fluorescence spectroscopy and nuclear magnetic resonance (NMR). Using two denaturants, guanidine and urea, the stability of flavodoxin was altered under encapsulation using different surfactants. These findings lay the groundwork for a comprehensive analysis of flavodoxin stability using reverse micelles. Future studies will include fluorescence- and NMR-based unfolding experiments in reverse micelles of varying composition to extract global and site-resolved insight into flavodoxin interactions with reverse micelle interfaces to elucidate the effect of confinement on overall stability of the protein.
24. Nadia Afrin
MS in Pharmaceutical Sciences
Advisor: Thomas Keck
Title: Widening the Opioid Analgesia Therapeutic Window with a Dual Pharmacology Strategy
Abstract: Morphine, an opioid analgesic, activates µ-opioid receptors to block the nociception process in the periphery and in the central nervous system. Opioids have important side-effects, including abuse liability and potentially lethal respiratory depression. Identifying new treatment strategies for analgesia may help to address patient needs and the current opioid endemic. α2/α3 subunits-containing GABAA receptors are expressed in the spinal cord and benzodiazepine-like positive allosteric modulators (PAMs) targeting these receptors produce antihyperalgesia. We have previously established that MP-III-024, a novel α2/α3 GABAA PAM, produces antinociception when co-administered with morphine. Current follow-up studies are evaluating whether MP-III-024 affects morphine-induced side effects. This study used plethysmography testing to observe whether MP-III-024 co-administration alters morphine-induced respiratory depression effects in male CD-1 mice. Folllowing habituation, mice received cumulative doses of morphine, MP-III-024, or morphine and MP-III-024 in a 1.00: 0.94 ratio (which produces peak synergistic analgesic effects). Morphine had a biphasic response, increasing the tidal volume (TVb) at a low dose, and dose-dependently reducing breathing rate (f) at higher doses. MP-III-024 reduced TVb at the highest tested dose. The combined delivery of morphine and MP-III-024 did not produce any significant effect on the tidal volume (TVb) or breathing rate (f). Data indicating that MP-III-024 may actually provide a protective effect against opioid-induced respiratory depression. Ongoing and future studies will investigate the neurological mechanisms that might explain this effect.
25. Lilliana De Salas
MS in Complex Biological Systems
Advisor: Nicholas Whiting
Title: Green Synthesis of Carbon Quantum Dots using Dried Flowers
Abstract: Carbon-based quantum dots are valued for their favorable optical and electronic properties while being inexpensive and biologically-friendly. While most carbon dots are synthesized from the bottom-up using small-molecule precursors, different types of plant and agricultural wastes can also be transformed into carbon dots using green chemistry. Here, we synthesized carbon quantum dots using hydrothermal solvation of dried rose petals and lavender buds. Samples were then purified, and the physical and chemical properties of the carbon quantum dots were characterized. Long-term, we aim to develop these carbon dots as agricultural supplements.
26. Daniel Arango-cardona
MS in Bioinformatics
Collaborators: Grace Bonnell
Advisor: Jason Heindl
Title: Regulation of Phenotypes Through Manipulation of sRNA AbcR1 and AbcR2 through its Motif.
Abstract: Agrobacterium tumefaciens is an important plant pathogen that causes crown gall disease on hosts. Critical to pathogenesis are several complex phenotypes, including biofilm formation and flagellum-mediated swimming motility. This is regulated by a LysR-type transcriptional regulators (LTTR) called VtlR which plays a role in expressing developmental phenotypes. This LTTR directly regulates two small RNAs which share target genes. These two regulatory small RNA (sRNA) species, AbcR1 and AbcR2, are hypothesized to contribute to ecological fitness of the bacterium in dynamic and unstable environments, including when associating with host plants. These small RNAs have been identified by RNA-seq to regulate large sets of gene and some are shared with the absence of one or the other. We hypothesize that the M1 motif (CUCCCA) in AbcR1 is a primary determinant of AbcR1-dependent gene expression in A. tumefaciens. We show that AbcR1 plays a more prominent role in regulating these phenotypes, relative to AbcR2, most likely due to the presence of a conserved motif (M1) which is absent in AbcR2.
27. Gabrielle Salvatore
Post-Doctoral Fellow
Advisor: Danielle Arigo
Title: Women’s Experiences with Mobile Applications for Self-Monitoring of Physical Activity and the Menstrual Cycle
Abstract: Menstrual cycle (MC) experiences (e.g., pain) may impact women’s physical activity (PA) engagement; traditional gender roles and associated perceptions (e.g., not an acceptable “excuse” for low PA) create barriers to understanding the MCs role in women’s PA. Mobile applications (apps) may offer a solution by capturing time-sensitive data (i.e., without interpersonal disclosure). However, a US Supreme Court decision restricting access to reproductive healthcare raised concerns about the use of MC apps in research, as data may be used to prosecute women for accessing certain procedures (e.g., abortion care). This study was designed to explore women’s experiences with apps for self-monitoring of health experiences (e.g., MC, PA) and examine women’s willingness to use such apps for research purposes in the current cultural and legal context. During 8 weeks following the court decision, 110 women living in the US completed an anonymous survey (MAge = 31.8, MBMI = 26.3 kg/m2, 73.6% White). Many respondents had experience using MC tracking apps; 46% were current users and 20% had used such an app in the past. Over one-third (37.6%) reported reconsideration of MC app use due to events in the US, 29% preferred a non-app based method of MC tracking for research, and 40.9% reported that they are not willing to participate in research that involved MC tracking. Additionally, 62.7% used a PA tracking tool and 30% used other mobile health apps (e.g., calorie intake). Findings show that despite the popularity of digital self-monitoring, many menstruating women have concerns about app-based MC tracking that may establish a timeframe of pregnancy - including data collected in a research context. To fully understand how MC experiences impact women’s PA, additional information is needed to establish criteria and protections for use of mobile apps in behavioral research.
28. Adriann Lai
PhD in Clinical Psychology
Advisor: Thomas Dinzeo
Title: Effort and Cost in Decision Making: Implications for Health Behaviors in Schizophrenia Spectrum Disorders
Abstract: Avolition and anhedonia are prominent negative symptoms in schizophrenia spectrum disorders (SSDs that impact the fundamental processes of motivated behaviors. Effort-cost decision-making (ECDM) impairments have been proposed as a neurobiological mechanism contributing to motivational deficits in SSDs, suggesting individuals may overvalue the effort required for rewards. The Effort Expenditure for Rewards Task (EEfRT) serves as a paradigm to study ECDM and has shown individuals with schizophrenia exert less effort for rewards compared to controls. However, it is unclear when these motivational deficits first emerge. Two recent studies found evidence for reward processing deficits with increasing levels of schizotypy (i.e. subclinical risk-indicators for schizophrenia), although their findings were somewhat inconsistent, warranting further investigation. The symptoms of “negative schizotypy”, characterized by social withdrawal and difficulties with emotional expression, appear to be particularly connected to incentive-motivation deficits. The current study aims to examine incentive-motivation relationships in students exhibiting risk indicators for SSDs. We hypothesize participants with high negative symptoms will show reduced effort for increasing rewards on the EEfRT, indicative of anticipatory pleasure deficits. Additionally, we predict amotivation will correlate with problematic health behaviors which may contribute to the high rates of chronic health conditions documented in SSDs. The study will also explore EEfRT performance in two other symptom domains of schizotypy (i.e., “positive”, involving delusion- and hallucination-like experiences; and “disorganized”, involving troubles with focus/attention, communication, and odd behavior). Understanding decision-making in schizotypy may inform risk indicators for future problematic health behaviors development in SSDs. Data will be collected from undergraduate students recruited from Rowan University, utilizing the EEfRT paradigm and various questionnaires to assess schizotypy traits, lifestyle habits, and pleasure experiences. Results will elucidate the role of motivational deficits in SSD precursor states and their implications for health behaviors.
29. Alicia Petrany
MS in Bioinformatics
Advisor: Yong Chen
Title: Detangling gene expression dynamics through the probabilistic and deep learning-based modeling of scRNA-seq data
Abstract: Single cell RNA sequencing (scRNA-seq) data facilitates the quantitative examination of gene expression levels at a cellular level, allowing for the investigation of transcriptional regulatory systems. Traditional analysis workflows typically involve comparative analysis to discern translational distinctions between different cellular phenotypes, such as cancerous versus non-cancerous cells. Differential expression (DE) analysis, the predominant method for comparative analysis, identifies statistically significant upregulated or downregulated genes. Current DE analysis approaches rely on heuristic or empirical techniques for significance determination. In this work, we derive the underlying theoretical distribution for comparative analysis of scRNA-seq data, termed the difference of two negative binomial distributions (DOTNB). DOTNB demonstrates superior performance compared to existing DE analysis methods across both real and simulated scRNA-seq datasets. Furthermore, DOTNB is extended to detect co-differential gene (CDE) expression, identifying clusters of genes with similar expression profile shifts in response to cellular phenotypes or stimuli. DE genes identified using DOTNB are input into a high-order deep multiplex infomax (HDMI) , which is a deep learning approach to conducting self-supervised embedding on multi-layered networks with external metadata. This method clusters genes based on similarities within their DE profiles, yielding modules of CDE genes. This method was applied to reveal regulatory differences between related neural cell types, providing novel insights into cellular heterogeneity within the neural landscape.
30. Jamie Clapp
PhD in Materials Science and Engineering
Advisor: Erik Hoy
Title: Active space selection: utilizing periodic-like active space design principles and pyRUQT for single-molecule nanoelectronics
Abstract: The field of single-molecule nanoelectronics is a widely studied area of research due to the distinctly quantum nature of their charge transport properties. A quantum charge transport property that continues to be a challenge in particular is the inclusion of multireference electron descriptions within the quantum mechanical models used. To further understand multireference effects, a Python module-based framework, pyRUQT, was developed. This grants the ability to pair Non-Equilibrium Green’s Function (NEGF) calculations with multiconfigurational-pair density functional theory (MC-PDFT) calculations which uses active space to treat multireference correlation. This results in a key new challenge to address: the active space design and selection for the system, as both the metal electrodes and central device region must be considered in unison. We propose a design principle based on unifying the two regions in a periodic-like pattern in order to simplify the NEGF transport calculations and ultimately improve transport properties. It was found that better alignment had better transmission/conductance, and vice versa poor alignment showed non-transmission/conductance. This leads to potentially finding different levels of transmission based on which orbitals are chemically more important. This approach will be further implemented in future studies with larger systems, including supercell approaches and larger metal electrode systems.
31. Kasmier Vicioso
PhD in Pharmaceutical Chemistry
Advisor: Rashanique Quarrels
Title: Visible-light Mediated Photocatalytic Reduction of Aryl Sulfonates
Abstract: Protecting groups play a huge role in synthetic organic chemistry. The addition and elimination of groups to preserve a key functional group throughout a synthesis can sometimes require harsh conditions, such as strong acids or bases, and prove to be costly. Tosylates in particular are a common alcohol protecting group that also serves as a good leaving group. However, reagents used for deprotection of aryl tosylates such as samarium iodide, palladium, or trimethylsilyl chloride in refluxing solvent provide moderate yields. More recently, sulfonates have been explored as photoremovable protecting groups. In contrast, we hypothesize that the use of organic photocatalysts can be used to deprotect aryl tosylates under visible light photocatalytic conditions. These mild conditions to cleave the S-O tosylate bond to generate phenols are an untapped space in organic chemistry with the potential to be used in late-stage deprotections.
32. Ariel Zhang
PhD in Complex Biological Systems
Advisor: Melissa Manners
Title: Investigating morphology and activation of astrocyte via chronic stress-induced inflammation in the brain
Abstract: Chronic stress is a major precursor to various neurodegenerative disorders and closely associated with increased inflammation in the brain. However, the bidirectional association between inflammation and chronic stress has yet to be fully understood. Astrocytes are one of the key inflammatory regulators in the brain. When activated, reactive astrocytes become neurotoxic and proinflammatory. In this study, we evaluated the chronic stress-induced inflammation in multiple brain regions by examining the morphological changes of astrocytes. We conducted the Unpredictable Chronic Mild Stress (UCMS) paradigm to model chronic stress, and lipopolysaccharide (LPS) administration to induce systemic inflammation in mice. Branching and terminal points of astrocytes were quantified using Imaris. Schoenen ramification index and Sholl analysis were performed to analyze astrocytes morphology and activation. Chronic stress induced significant morphological changes in astrocytes similar to systemic inflammation in all key brain regions. Astrocytes were highly ramified with increased bifurcation and terminal points from the cell body compared to the control group. Sex differences was also observed in astrocytes from hippocampus, prefrontal cortex, hypothalamus, amygdala, periaqueductal grey. The result indicated that chronic stress induced inflammation in the brain through astrocyte activation in multiple brain regions.
33. Annie Tran
M.S Pharmaceutical Science
Advisor: Chun Wu
Title: Investigating HIV-1 virus evolution to see if it follows the Near Near-Neutral Balanced Selection Theory (NNBST)
Abstract: Human immunodeficiency virus type 1 (HIV-1) is a single-stranded RNA retrovirus containing 9,181 nucleotides. Vaccine approval for HIV-1 is challenging due to the high mutation rate that allows the virus to evade and adapt to the immune system and antivirals. The current understanding for the molecular evolution of HIV-1 is believed to follow Kimura's neutral theory (KNT), in which mutations are neutral and do not affect the virus’ fitness. Yet, KNT cannot exclusively explain the high adaptability of this virus, suggesting it may undergo Darwin’s Natural Selectionist Theory (ST). But can either theory explain the evolution of this virus? Our recently proposed Near neutral balanced selection theory (NNBST) is a hybrid theory combining ST, KNT and Ohta Nearly-Neutral Theory (ONNT) to explain the true molecular evolution of SARS-CoV-2. The molecular evolution of HIV-1 may follow NNBST. By utilizing the reference sequence of the complete genome of HIV-1, the relative substitution rate to mutation rate (c/µ) of each of the nucleotide/amino acid sites can be calculated. Additionally, the number of nonsynonymous substitutions (Ka, mutations change in protein sequence) and synonymous substitutions (Ks, mutations do not change in protein sequence) are determined. Through calculating c/µ and Ka/Ks of the reference sequence, the new proposed theory may exhibit NNBST (Near neutral balanced selection theory) of the following L-shape distribution graph to prove its true molecular evolution of HIV-1.
34. Julia Gabriel
PhD in Pharmaceutical Chemistry
Collaborators: Jesse Na
Advisor: Erik Hoy
Title: Controlling Enol-Keto Tautomerization Ratios using Electronic Structure Effects
Abstract: Tautomeric equilibria play an essential role in a wide array of natural chemical and biological reactions. Despite having structures that only differ by the position of one hydrogen atom, the chemical/biological properties of tautomers can vary considerably. As a result, the key question that we seek to answer for this project is “what fundamental chemical/electronic structure factors can control the equilibrium ratio between the keto and enol forms of a molecule?” Before attempting to solve this, we needed software that aids computational quantum chemistry. Gaussview and Maestro are exceptional tools that were used in order to run calculations to obtain our data. As the first step to answering this question, we examined both known and novel keto/enol tautomer compounds to identify factors that play the largest role in determining tautomer equilibrium. We analyzed the impact of substituent effects, intermolecular interactions, and solvent interactions (implicit and explicit) on the tautomerization ratio using a variety of DFT methods and basis sets. We were able to understand our result through the resulting value of total free energy through our calculations. A negative value would result in the structure favoring the keto form while a positive value would result in the structure favoring the enol form. In this presentation, we will discuss which of these factors plays the largest role in determining the theoretical equilibrium and how certain known trends further validate these findings. These observations will then be used to guide future experiments as well as finding better ways to improve our theoretical methods.
35. Bamidele Towolawi
PhD in Pharmaceutical Chemistry
Advisor: Zhiwei Liu
Title: Computer Aided Design of Aromatic Foldamer Targeting Protein-protein Interaction
Abstract: With the computational tools developed in our lab for accurate prediction of structures and solution dynamics of aromatic foldamers, we now target protein-protein interaction (PPI) by appending proteinogenic side chains on the external surfaces of the helical aromatic foldamers. Particularly, the activation of a regulatory protein NF-κB, a key player in the inflammatory response and cell proliferation, involves binding of NEMO (NF-κB Essential Modulator) with linear di-ubiquitin. In this study, we designed various sequences based on established protocols and investigated, by utilizing molecular dynamics (MD) simulations, their potential binding to di-ubiquitin, specifically targeting the NEMO binding interface. This study complements experimental works related to synthesis, characterization, and crystallization of aromatic foldamers. Here, we present structural analysis of MD trajectories from simulations of 21 aromatic foldamers/di-ubiquitin systems with explicit solvent (aqueous) to gain insight into the binding interaction.
36. Rosalind Moore
PhD in Complex Biological Systems
Advisor: Matthew Farber
Title: Seed sterilization and processing protocol for endophytic microbiome in barley
Abstract: Improving Winter Barley Hardiness using Endophytic Microbiome
Barley is a major cereal crop in global agriculture, with an average annual acreage of 48 million hectares, yet the USDA reported a decline in yield for the past ten years. Previous research has shown that a diverse endophytic microbiome can improve yield and resistance in other crops. This study aims to compare the endophytic microbiome of wild barley with industrial cultivars with the hypothesis that cultivars have lost the biodiversity commonly seen in wild populations. We aim to transfer a wild barley endophytic microbiome to the cultivated variety seed, to improve growth and yield in the field. Amplicon sequencing will be utilized to determine species richness and abundance of each barley sample and community-level biodiversity metrics will be employed to assess variance across species and growing conditions. Grain quality and yield, drought resistance, and temperature resistance will also be measured to determine effects of endophytic community on agriculturally important barley cultivar traits. Beyond barley, this work may serve as a scaffold for further research on a host of other vital crop plants.
37. Sravani Malasani
PhD in Pharmaceutical Chemistry
Advisor: Zhihong Wang
Title: Biophysical analysis of Kras Mutants with N-terminal RAF isoforms
Abstract: The RAS-RAF-MEK-ERK signaling pathway is essential for cell division, growth, and reproduction. Within this system, oncogenic RAS is mostly mediated by the serine/threonine kinase RAF, which is commonly mutated in human cancers. As per the approved model, activated RAF kinase is membrane recruited via RAS-GTP and dimerized, whereas inactive RAF kinase is monomeric, autoinhibited, and cytosolic. However, many questions about how the association with Ras results in the activation of the kinase domain remain unanswered. The mutated form of the K-Ras is commonly observed in Malignant tumors. Pancreatic, Lung, and colon cancers predominantly exhibit the mutant version of K-Ras. To investigate further the Ras-RAF interactions, we have successfully cloned the KRAS mutants. Our aim is to investigate the binding kinetics between N-terminal Raf isoforms and mutated KRAS. We successfully conducted biophysical assays and quantified the in vitro binding between the N-terminal domains of BRAF and KRAS Mutants using Surface Plasmon Resonance (SPR). The objective of this study is to generate peptides that possess inhibitory properties.
38. Mohammad Alkhatib
MS in Pharmaceutical Sciences
Advisor: Thomas Keck
Title: Enhancing Ligand Pharmacokinetics While Retaining Dopamine D4 Receptor Potency and Selectivity via Bioisosteric Substitution of Amide Linkers with 1,2,3-Triazoles
Abstract: The neurotransmitter dopamine signals through G protein-coupled receptors to modulate various neurophysiological functions. Activation of dopamine D4 receptors (D4Rs), predominantly located in the brain's prefrontal cortex and hippocampal regions, can modulate memory formation, attention, decision-making, and cognition. Prior studies indicate that D4R-selective ligands are efficacious in preclinical models of cognitive disorders and substance use disorders. Recently, we reported a library of novel D4R-selective ligands with varying efficacies for further preclinical study. Unfortunately, these compounds exhibited rapid in vivo metabolism precluding proper evaluation of their behavioral effects. In vitro pharmacokinetics (PK) studies revealed that the primary route of drug metabolism was the cleavage of an amide linker present in the scaffold of these compounds. In this study, we bioisosterically replaced the amide bond with a 1,2,3-triazole linkage using click chemistry methods and evaluated triazole analogs against their amide counterparts in binding, functional, and PK studies. Our results indicate that 1,2,3-triazole analogs sustained high D4R binding and selectivity over dopamine D2 and D3 receptors. Overall, triazole analogs have markedly similar functional profiles at D2-like receptors, indicating no loss of in vitro function. Finally, liver microsome studies, replacement of the amide linkage with a 1,2,3-triazole substantially increases drug half-lives in rats with minor improvements in humans, and eliminates non-Phase I metabolism (i.e., via amidases). These new analogs represent a set of new molecular tools better equipped to further explore D4R signaling in rodent models of neuropsychiatric disorders.
39. Kevin Daus
PhD in Complex Biological Systems
Advisor: Mary Alphaugh
Title: ARCAM fluorescent probes as an in situ protein sensor
Abstract: Communication between cells within the tumor microenvironment (TME) is accomplished through soluble factors (e.g. proteins), often in a concentration-dependent manner. A small fluorescent probe, ARCAM binds non-specifically to hydrophobic pockets of proteins; in its bound-excited state it undergoes a conformational change releasing a photon as it relaxes to ground state. The linear relationship between viscosity (i.e., protein concentration) and fluorescent emission of ARCAM results in the accurate protein quantification within the TME. The ARCAM platform is comparable to the commonly used protein assays, namely Bradford-lowry and BCA. ARCAM provides the added advantage to these assays in that it is non-toxic (i.e., cellular compatibility) and non-terminal allowing for in situ protein sensing.
40. Robyn Himelstein
MA in Psychology
Advisor: Katherine Gotham
Title: The Longitudinal Relationship between Social Motivation and Depressive Symptoms in Autistic Adults
Abstract: Depression is one of the most common and clinically significant co-occurring conditions autistic adults face. Determining pathways to depression is essential for identifying treatment targets. Han et al. (2019) observed that autistic adults who reported high social motivation but low social engagement were more likely to endorse loneliness, with loneliness then predicting depressive symptoms. However, that study’s cross-sectional design limited the implications of these variables as prospective contributors to depression in autism. We investigated longitudinal relationships between social motivation, social access (i.e., having opportunities for meaningful social interactions), loneliness, and depression in autistic adults at three timepoints (T1–T3). We predicted that T2 loneliness would mediate the relationship between T1 social access and T3 depression. We predicted an interaction between T1 social motivation and social access, such that participants who reported higher social motivation and lower social access would subsequently report higher loneliness and depressive symptoms; we hypothesized that this interaction would prospectively predict depression symptoms at T3. Autistic adults (N=303) aged 18-60 were recruited through the Simons Foundation Powering Autism Research for Knowledge (SPARK) cohort, an online autism registry. Participants completed online surveys three times over 3–4 months, measuring autism traits, social motivation, loneliness, social access, and depression. Results supported a baseline model of loneliness mediating the relationship between social access and depressive symptoms. We found little evidence of social motivation as a moderator of any paths in this model. Thus, we could not conclude that an interaction between high social motivation and low social access prospectively predicted loneliness and depression. We discuss our results considering challenges in measuring social motivation, operationalizing “social access,” and possible bidirectional effects of social motivation and depressed mood that unfolded pre-study. The findings highlight the importance of supporting meaningful social opportunities for all autistic adults, not just those who desire social interaction.
41. Erin McKenney
Ph.D. in Clinical Psychology
Advisor: Katherine Gotham
Title: Repetitive negative thinking as a prospective predictor of depression and anxiety symptoms in autistic and non-autistic incoming college students
Abstract: Background: Improving the understanding and treatment of mental health concerns, including depression and anxiety, are significant priorities for autistic adults (Benevides et al., 2020; Crane et al., 2019; Pellicano et al., 2014). While several theories have been proposed to explain the high prevalence of internalizing symptoms in autistic people, little longitudinal research has been done to investigate potential causal mechanisms. One potentially fruitful area of investigation is to explore how well-known contributors to depression/anxiety in the general population predict and/or moderate the development of internalizing symptoms in autistic individuals. Objectives: The current study investigates the relation of one established risk factor from the general population, repetitive negative thinking (RNT), to internalizing symptoms over the course of college students’ first semester. We will also examine whether this association is moderated by a measure of autistic traits (Social Responsiveness Scale, Second Edition; SRS-2; Constantino & Gruber, 2012) and self-described autism status. Methods: Students were recruited from four northeastern United States universities prior to their first semester at their university (in Fall 2020, Fall 2021, and Fall 2022). Our sample (N=263 total) includes 105 students who either reported a formal autism diagnosis (n=30) or endorsed a history of self and/or others thinking that they may be autistic (n=75), as well as 158 students with no history of autism. Participants completed a baseline survey battery within their first two weeks of starting college, a brief biweekly survey throughout their first semester (up to 24 times across 12 weeks), and an endpoint packet. Cross-sectional and longitudinal relationships of interest were assessed using general linear models and generalized least squares (GLS) regression (Pinheiro & Bates, 2000) with a first-order autoregressive correlation structure (AR1), respectively. Results: Cross-sectional analyses on the full dataset (N=263) indicate that autistic (self-identified or clinically diagnosed) students tended to report greater repetitive thinking (F(1,252)=42.40, p<.001, d=0.83), as well as higher depression (F(1,257)=25.20, p<.001, d=0.64) and anxiety (F(1, 256)=26.49, p<.001, d=0.65) symptoms at baseline. Longitudinal analyses on the Fall 2020 and 2021 cohorts (n=144) demonstrated that elevated trait-like RNT at baseline prospectively predicted biweekly ratings of sadness (b=0.04, CI95%: 0.03, 0.05, f2 =0.11), anhedonia (b=0.04, CI95%: 0.03, 0.05, f2 =0.12), and anxiety (b=0.04, CI95%: 0.03, 0.05, f2 =0.11) symptoms across the semester, when controlling for SRS-2 scores and time trend . A third wave of data will be added in January 2023 to supplement these longitudinal analyses. Conclusions: These preliminary findings highlight RNT as a specific predictor of depression/anxiety that extends across neurotypes but may be especially prevalent in autistic adults. If causality continues to be supported, then RNT may be an important intervention target toward reducing the elevated depression and anxiety rates within the autistic community. Understanding common factors in depression and anxiety treatment across populations may additionally assist in increasing clinician confidence and competence in treating the underserved population of autistic adults with mood disorders (Maddox et al., 2020).
42. Khanh Pham
PhD in Clinical Psychology
Advisor: Jonathan M. Lassiter
Title: Black Boys OM: a case study of the impacts of community and culture on wellness practices
Abstract: Black men continue to face health disparities due to systemic oppression. Research indicates that mind-body-spirit practices (MBSPs) can effectively improve mental and physical health, thereby reducing health disparities among Black men. However, MBSPs are often White-female-dominated practices, thus putting Black male practitioners at continued risks of under-representation and marginalization in MBSP spaces. The culturally specific nature of MBSP spaces may then be an important factor in MBSPs’ influence on Black men’s health. Therefore, we aimed to explore how culturally specific MBSP spaces impact Black male practitioners’ MBSPs. We collaborated with Black Boys OM (BBO), a global community of Black male mind-body practitioners, and utilized a case study-mixed methods approach to examine how BBO impacts Black male practitioners’ MBSPs. We conducted individual interviews (median length = 41 minutes) with the participants, 17 Black male yoga instructors from BBO, to learn about their experiences with BBO and other MBSP spaces. We utilized a hybrid qualitative approach that combined elements of codebook and reflexive thematic analysis to analyze our transcripts. We generated four categories of meanings to describe how the participants viewed BBO’s impact on their MBSPs. These categories included: 1) Black male mind-body practitioners’ needs, 2) the nature of mainstream MBSP spaces, 3) benefits of BBO, 4) requests for BBO. Finally, we discuss our findings and their implications for Black men’s health.
43. Sravani Malasani
PhD in Pharmaceutical chemistry
Advisor: Zhihong Wang
Title: Biophysical analysis of Kras Mutants with N-terminal RAF isoforms
Abstract: The RAS-RAF-MEK-ERK signaling pathway is essential for cell division, growth, and reproduction. Within this system, oncogenic RAS is mostly mediated by the serine/threonine kinase RAF, which is commonly mutated in human cancers. As per the approved model, activated RAF kinase is membrane recruited via RAS-GTP and dimerized, whereas inactive RAF kinase is monomeric, autoinhibited, and cytosolic. However, many questions about how the association with Ras results in the activation of the kinase domain remain unanswered. The mutated form of the K-Ras is commonly observed in Malignant tumors. Pancreatic, Lung, and colon cancers predominantly exhibit the mutant version of K-Ras. To investigate further the Ras-RAF interactions, we have successfully cloned the KRAS mutants. Our aim is to investigate the binding kinetics between N-terminal Raf isoforms and mutated KRAS. We successfully conducted biophysical assays and quantified the in vitro binding between the N-terminal domains of BRAF and KRAS Mutants using Surface Plasmon Resonance (SPR). The objective of this study is to generate peptides that possess inhibitory properties.
44. Pintu Miah
MS in Pharmaceutical Sciences
Advisor: Thomas Keck
Title: Exploring the Analgesic Effects of Dopamine D3 Receptor Negative Allosteric Modulators (D3 NAM)
Abstract: Pain management remains a critical aspect of healthcare, necessitating the constant search for novel analgesic targets and compounds. The dopamine D3 receptor has emerged as a potential player in modulating pain perception, making it an intriguing target for analgesic drug development. This study investigated the analgesic and behavioral effects of a novel Dopamine D3 negative allosteric modulator (D3 NAM), UNC6869, in mice using the hot plate test and assessing locomotor activity. Male mice were administered 0, 40, and 80 mg/kg doses of UNC6869 using a cumulative dosing paradigm. In the hot plate assay, their response to thermal stimuli was measured by time to nocifensive behavior. Results demonstrated a dose-dependent increase in the latency to nociceptive responses, suggesting a potential analgesic effect mediated by UNC6869 D3 NAM modulators. In the locomotor assay, UNC6869 produced no significant alteration in overall activity. Analysis of treated animals 24-48 hours after testing, however, revealed evidence of drug-induced toxicity. Postmortem analyses indicate that UNC6869 may have induced toxic effects in the liver and/or the gastrointestinal tract. Follow-up efforts are underway to test two new D3 NAMs (UNC7108 and UNC8747) believed to have chemical modifications that might reduce toxicity in similar behavioral tests. Furthermore, detailed histological analyses will be performed on mice treated with UNC6869, UNC7108, and UNC8747 in order to identify plausible mechanisms of toxicity and to determine whether UNC7108 and UNC8747 have improved safety profiles. Overall, these studies explore the promising analgesic properties of D3 NAMs and highlight the importance of toxicology when testing a new class of compounds.
45. SHAKIL AHMED
MS in Pharmaceutical Sciences
Advisor: Thomas Keck
Title: A Role for Prior baseline activity in psychostimulant-induced locomotor activity sensitization
Abstract: The current health crisis of psychostimulant use disorders (PUDs) lacks effective FDA-approved pharmacotherapeutic options. PUDs result from repeated use of psychostimulants, which have been shown to cause sensitization—an increase in the drug's effects with repeated administration. However, the mechanism of sensitization remains unclear. Research suggests that individuals with lower baseline activity are more susceptible to psychostimulant-induced effects. Our study aimed to investigate the role of baseline activity in psychostimulant sensitization. We experimented on male Sprague-Dawley rats, measuring their locomotor activity following cocaine injections with and without prior repeated cocaine-10 mg/kg i.p. (or saline) injections for 14 days. We estimated baseline activity, drug activity, and drug effects, which we calculated as a percentage change in drug activity from baseline activity. To analyze our data, we used both ANOVA and linear regression analysis. Our analysis revealed that cocaine increased locomotor activity, and sensitization occurred with repeated administration. Furthermore, we found that a change in baseline activity between day 1 and day 14 could explain cocaine-induced locomotor sensitization.
46. Okikiola Agbabiaka
PhD in Materials Science and Engineering
Advisor: James Newell
Title: Mathematical Modeling and Optimization of Cold Spray Deposition for Enhanced Efficiency: A Case Study on Polymeric Materials in the Context of Nylon 6 Powder and Nylon 6 Substrate
Abstract: This work delves into the use of cold spray technology in the additive manufacturing of polymers. Cold spray technology, unlike conventional methods such as directed energy deposition (DED) and thermal spray, operates without melting the precursor material. It utilizes supersonic speed to propel particles to a substrate, allowing them to bond through plastic deformation. Despite the high performance, strength, and low weight of polymers making them ideal candidates, challenges arise due to the nature of polymer bonding, entanglement, and potential for mechanical deformation. This research aims to develop a constrained model using statistical methods to predict near-optimal spray conditions for previously unsprayed polymeric materials. The model offers a simpler and more efficient approach than complex AI algorithms or machine learning, requiring fewer experiments. This work also highlights the importance of understanding the chemical and physical aspects of polymer cold spray for successful model application to different polymer systems.
47. Adarsh Kumar
PhD in Pharmaceutical Sciences
Collaborators: Emily Nelson
Advisor: Erik Hoy
Title: Low Temperature Depolymerization Reversible Addition Fragmentation Chain transfer Polymers : Effect of Z-group
Abstract: Reversible Addition Fragmentation Chain Transfer (RAFT) polymerization has revolutionized the field of polymer science by enabling precise control over polymer architectures. However, understanding the depolymerization process is equally crucial for designing sustainable and efficient materials. In this study, we delve into the intricate world of RAFT depolymerization, focusing on radical generation, energy landscapes, and potential transition states. RAFT polymerization involves reversible activation/deactivation radical polymerization, where the RAFT agent mediates the equilibrium between active radicals and dormant species. While RAFT polymerization leads to the formation of well-defined polymer chains, depolymerization remains less explored. Our investigation aims to shed light on the fundamental processes governing RAFT depolymerization. We selected representative RAFT agents and employed computational chemistry tools to predict their depolymerization behavior. Specifically, we utilized Schrödinger Maestro and Gaussian software packages to analyze the energy requirements for breaking polymer chains. At the end some upcoming application areas of polymers prepared by RAFT are presented.
48. Atik Faysal
PhD in ECE
Advisor: Huaxia Wang
Title: Bootstrap Your Whole Latent: Self-Aware Representation Learning Meets Pseudo Labeling
Abstract: Bootstrap Your Own Latent (BYOL) is a semi-supervised representation learning method for image classification. It uses labeled and unlabeled data to learn representation using two neural networks called online and target networks. However, despite being state-of-the-art (SOTA), BYOL does not use its full potential. We identify two major issues: 1. BYOL uses two augmented images to learn representation but never the original image; 2. during the downstream task of BYOL, the unlabeled data stays unused. Our method uses the original image with augmented images and passes it through the online network. We add a weighted loss term to the original loss to update the network with the additional input. This modification achieves an improved accuracy. Once the supervised model is trained, we apply a modified Meta Pseudo Labels (MPL) to utilize the unlabeled samples. Our proposed method is called Bootstrap Your Whole Latent (BYWL) and is 2.7\% more accurate than the original BYOL on the STL-10 dataset.
49. Mohammad Rostami
PhD in ECE
Advisor: Huaxia Wang Title: Meta-Tasks: Improving Robustness in Few-Shot Classification with Unsupervised and Semi-Supervised Learning
Abstract: Few-shot learning (FSL) is a challenging machine learning problem due to a scarcity of labeled data. The ability to generalize effectively on both novel and training tasks is a significant barrier to FSL. This paper proposes a novel solution that can generalize to both training and novel tasks while also utilizing unlabeled samples. The method refines the embedding model before updating the outer loop using unsupervised techniques as ``meta-tasks''. The experimental results show that our proposed method performs well on novel and training tasks, with faster and better convergence, lower generalization, and standard deviation error, indicating its potential for practical applications in FSL. The experimental results show that the proposed method outperforms prototypical networks by 3.9\%.
50. Taha Bouhsine
MS in Electrical and Computer Engineering
Advisor: Nidhal Bouaynaya
Title: SeeNN: Seeing the Unseen with a Modality Fusion Framework for Long-Range Atmospheric Visibility Estimation
Abstract: Deep learning (DL) models have attained state-of-the-art performance in numerous fields. Nevertheless, for certain real-world applications, existing models encounter diverse challenges, ranging from a lack of generability to new data to issues of scalability and overfitting. In this context, the integration of information derived from multimodal data holds promise as a potential solution to alleviate these challenges. This paper introduces SeeNN, an innovative DL framework for long-range atmospheric visibility estimation. Leveraging multimodal fusion, SeeNN integrates diverse data sources to accurately perceive atmospheric conditions over extensive distances. This research addresses the challenge of limited visibility data in adverse weather conditions, offering a novel approach that enhances both accuracy and reliability in visibility estimation. The proposed framework's effectiveness is demonstrated through rigorous testing and comparison with single modality models. SeeNN's potential for practical applications in various fields, including transportation and weather forecasting, is also explored. This study marks a significant advancement in atmospheric visibility estimation using multimodal DL techniques.
51. Giuseppina Carannante
Post-Doctoral Fellow
Electrical and Computer Engineering
Advisor: Nidhal Bouaynaya
Title: Trustworthy Medical Image Segmentation with Uncertainty Propagation
Abstract: Inspired by powerful statistical frameworks from target tracking in non-linear and non-Gaussian dynamical systems, I established the theoretical and algorithmic foundations of uncertainty quantification in encoder-decoder Deep Learning (DL) models, to achieve trustworthy segmentation of medical images. The proposed approach can simultaneously deliver the segmented image (prediction) along with the corresponding pixel-wise uncertainty map. The value proposition of proposed approach is two-fold: significant improvement in the accuracy under noisy conditions and adversarial attacks, and a learned uncertainty map that reflects higher uncertainty or decreased confidence for erroneous decision-making. I conducted an extensive noise and robustness analysis, considering both random and adversarial noise applied to three different medical imaging benchmark datasets and one clinical MRI dataset obtained from the University of Alabama at Birmingham School of Medicine. I showed that the uncertainty map associated low confidence (or high uncertainty) to regions in the input image that are corrupted with noise, artifacts, or adversarial attacks. These uncertainty maps provide crucial information about the network’s confidence, perhaps even self-awareness, in the reliability of its prediction. In particular, the uncertainty maps offer transparency that attracts the attention of supervising physicians. Most current clinical settings require a physician-in-the-loop when a DL system is deployed. The physician must review and, if needed, modify the decision of the model. Instead of having to review the entirety of the network's predictions, the physician is directed to areas of high uncertainty, where the network is least confident in its decision. In cases when the model may not be under direct and continuous physician control, it is even more important that the networks recognize high measures of uncertainty to generate an appropriate notification to the supervisor. Hence, this work paves the way to developing trustworthy and self-aware DL systems that can be safely deployed in mission-critical applications, such as healthcare.
52. Arunkumar Goli
Postdoctoral Fellow in Civil Engineering
Advisor: Yusef Mehta
Title: Sustainable Practices by New Jersey in Pavement Preservation Treatments
Abstract: Pavement preservation treatments possess a significant role in pavement maintenance as they are essential in avoid or delay the failure process and increase the pavement service life, skid resistance, driving comfort, and safety. Microsurfacing is one of the primary pavement preservation treatments that can restore the surface characteristics by enhancing the surface friction of pavements. Pavement recycling industry in New Jersey estimated around 10.8 million tons of stockpiled Recycled Asphalt Material (RAP) in 2018 whereas around 20% to 30% is being reused into pavement construction. In the context of New Jersey's Department of Transportation (NJDOT), these advancements in pavement preservation are especially relevant. Hence, New Jersey currently aims to maximize usage of RAP into different applications including parking drives, paths, and quarry fills etc., as the state moves ahead towards sustainability practices. Hence, the present study evaluated the feasibility of utilizing 100% RAP as an alternative to virgin aggregates (VA) as a potential material to produce microsurfacing while meeting all design requirements. This study utilized two sources of RAP and two sources of virgin aggregates, an unmodified and polymer modified asphalt emulsion for evaluating the design of virgin and 100% RAP microsurfacing mixes at laboratory. Further, the research team encountered few issues in the mix design and documented the reasons and solutions for the issues. A potential project location was selected for the construction i.e., Hammonton, New Jersey. APS performed the mix design for the construction and CREATES team verified the mix design. The process of placement of virgin and 100% RAP microsurfacing and key observations during the construction were documented in this report. Details of two distress surveys – one before the construction and one after the construction were conducted by the CREATES team to evaluate and compare the performance of 100% RAP microsurfacing with virgin microsurfacing.
53. Gali Lakshamana Ravi Raj
Postdoctoral Research Fellow
Title: A Comprehensive Study on Material Selection and Performance of Insulation Materials in Pavements
Advisor: Yusef Mehta
Abstract: Insulated pavement represents an innovative approach to safeguarding subgrade infrastructure from the adverse effects of subzero temperatures, including permafrost and upheaval. This research delves into the science behind insulation, emphasizing the critical need to protect subgrade from extreme cold, which can lead to permanent distresses in pavement. The primary focus is on preventing the subgrade from reaching subzero temperatures and undergoing permafrost-related issues. The study unfolds in two distinct phases. In Phase 1, extensive laboratory testing was conducted on various insulation materials, including XPS (Extruded Polystyrene), foam glass aggregates, tyre chips, and foam concrete. While XPS emerged as the most effective in insulating the subgrade, an intriguing discovery revealed its susceptibility to moisture over prolonged chilling periods, resulting in altered conduction properties. A thermo-mechanical coupled model was proposed during this phase. Recognizing the oversight of moisture in Phase 1, Phase 2 of the project is designed to comprehensively assess both the presence of moisture on insulation materials and their mechanical capabilities. The construction of a test section, utilizing the four insulation materials from Phase 1, aims to compare their performance in the presence of moisture and varying freeze-thaw cycles. This phase addresses the crucial aspect of moisture influence on insulation materials and its consequential impact on the overall effectiveness of insulated pavement. By bridging the gap left in the initial phase, this research aims to contribute valuable insights into the selection and performance of insulation materials in real-world conditions, enhancing the durability and functionality of insulated pavements in subzero surface environments.
54. Barnabas Gao
PhD in Chemical Engineering
Advisors: Kirtie Yenkie and Robert Hesketh
Title: Optimizing Oil Pipeline Flushing During Product Changeovers: A Bench-Scale Pilot Plant Study
Abstract: Flushing oil pipelines during product changeovers is a critical process in lube oil processing facilities to ensure the final product's quality and purity. This flushing operation results in large volumes of comingled products that are not packaged and sold at the high value of the pure products. So not only is there a financial loss, but the comingled oil product is not packaged, which lowers the product yield. To reduce both the financial and material losses, an innovative approach to optimizing this process is required. We have conducted a limited number of studies at the industrial plant, but need more data to optimize this process. These industrial studies were found to be both time-consuming and labor-intensive for an operating lube facility. It was found that these studies required substantial changes to the operating procedures in the plants and also resulted in excess downtime at the plant. To address these issues, a laboratory-scale pilot plant was designed and built to study and optimize the flushing process. A comprehensive review of lube oil properties, pipeline operations, and flushing processes in the lube oil industry will be studied with the pilot plant. Using the pilot plant, we are able to study the mixing of a residual oil with a flushing oil in a pipeline system. The pilot plant has been designed at a geometry ratio of 1/5 of the industrial plant. The flowrates in the pilot plant are based on matching Reynold’s numbers for the industrial plant. One advantage of the pilot plant is that we are able to vary the flowrate of the oil in the system using a positive displacement pump with a variable speed drive. This allows us to examine flows of identical Reynolds numbers to the industrial plant and examine an extended operating range of these flowrates (Scoffoni et al., 2001; Wang et al., 2011). With this pilot plant, we can not only obtain fluid samples and measure kinematic viscosity, similar to the industrial plant, but we also added an online measurement of the viscosity. We are also able to examine various pipeline system configurations with the pilot plant. This includes alternative filters, fittings, and piping. Also, in this pilot plant, we have studied pipeline coatings to determine if they will reduce the amount of residual oil that needs to be flushed. The research findings from this pilot plant are providing valuable data that are being used to formulate a model of this process. The bench-scale pilot plant provides a valuable tool for studying the flushing of oil pipelines during product changeovers in lube oil processing facilities. The novel approach will aid in the validation of models and the optimization of the flushing process, resulting in increased efficiency and product quality. The ability of the pilot plant to simulate industrial flush operations on a smaller scale provides a cost-effective and efficient solution for studying and optimizing the process while reducing the need for excessive operator time and plant visits.
55. Leeza Duller
MS in Engineering
Advisor: George Lecakes
Title: WaterCAVE: Virtual Reality for Engaging the Next Generation in Wastewater Management
Abstract: Within the next five to ten years, a significant portion of water and wastewater personnel are expected to retire, posing a substantial challenge for the utilities industry. The potential shortage of experienced workers poses inherent risks to the continuity of water services. WaterCAVE emerges as one of several tools designed to address this impending issue by engaging and inspiring the next generation to consider careers in the wastewater industry. This virtual reality (VR) simulation utilizes a ten-sided immersive display and was designed using Unity's 3D real-time development platform. Students from various educational levels, ranging from Pre-K to 12, are invited to participate in field trips at the Rowan Technology Park, where they can explore a virtual wastewater treatment plant. WaterCAVE introduces students to a customizable virtual tour guide, enabling them to navigate through the intricacies of wastewater treatment and interact with different personnel involved in operating a wastewater treatment facility. Through its innovative approach, WaterCAVE aims to spark curiosity and interest among the next generation, fostering a potential influx of future professionals into the wastewater industry.
56. Garrett Williams
MS in Electrical & Computer Engineering
Advisor: George Lecakes
Title: Virtual Reality to Generate Synthetic AI Training Datasets
Abstract: Advancements in Artificial Intelligence (AI) have enabled diverse applications, including the ability to detect and classify objects in real-time. To perform these object detection tasks, the AI algorithms must first be trained on large quantities of data. Within the domain of of aerial object detection, only a small amount of training datasets exists as obtaining real-world data is costly, dangerous, and inefficient. This work illustrates a virtual reality (VR) dataset generation tool called “DyViR” that creates annotated synthetic datasets of aerial objects based on the user’s specifications. Built using the Unity Real-Time Development Platform, DyViR allows customization of the environment, aircraft, and data formatting and generates hundreds of dataset images a minute. This allows for faster, safer, and more efficient production of datasets compared to their real-world counterparts. These synthetic datasets were used to train a YOLOv7-tiny AI model and demonstrated improved detection accuracy (mAP) versus using real-world data alone.
57. Austin Lehr
PhD in Chemical Engineering
Advisor: Kirti Yenkie
Title: The Role of Machine Learning in Early-stage Process Design and Sustainability: Predicting Environmental Impacts
Abstract: Early-stage process design plays a pivotal role in creating products and processes that are environmentally sustainable, yet the assessment of environmental impacts during this phase encounters significant challenges. Limited and uncertain information hinders the comprehensive evaluation of potential impacts, which is compounded by the complexity of data collection and the necessity for interdisciplinary collaboration. Machine learning, particularly the use of algorithms like Extreme Gradient Boosting (XGBoost), emerges as a valuable tool in predicting environmental impacts with scarce data, thereby enabling the development of sustainable designs from the outset. This study utilizes machine learning to predict the environmental impacts of chemicals, focusing on human health, ecosystem quality, climate change, and resource utilization. Adopting a novel approach, it integrates a cradle-to-cradle life cycle assessment (LCA) that incorporates solvent recovery at the disposal phase. Employing the XGBoost algorithm for its efficiency with large, complex datasets, the research analyzes 350 chemicals across various phases of their lifecycles', significantly reducing the feature data from 223 to 10 crucial features for accurate prediction. The methodology involves a detailed case study on Isopropanol (IPA), covering its production, usage, and end-of-life phases to demonstrate the model's applicability. The results show promising generalization capabilities for human health and global warming potential, though indicating a need for larger datasets to enhance predictions for ecosystem and resource utilization impacts. This approach underscores the importance of early-stage environmental impact prediction in fostering the design of more sustainable chemical processes and products.
58. Anil Kumar Baditha
Postdoctoral Research Fellow
Advisor: Yusef Mehta
Title: Use of Waste Plastics in Asphalt Mixes: Addressing the Variability of Source
Abstract: Use of waste plastics in asphalt mixtures suffers from a serious problem of significant variability with global sources; preventing proper guidelines for field applications. The aim of this study is to address the variability in source of waste plastic and its impact on asphalt mixture design. The study was designed to provide a selection criterion to evaluate the suitability of waste polyethylene (PE) for asphalt pavements. PE obtained from five sources was used as a replacement for asphalt binder. Dry mixing of plastics with asphalt and aggregate was performed at the dosage levels of 3%, 6%, and 9%. The changes in asphalt mixture volumetrics were correlated to plastic properties such as density(ρ), viscosity (η), melting point (Tm), and Degree of Crystallinity (Xc), apart from source. Construction Densification Index and Traffic Densification Index were also calculated for the workability of PE mixtures. From the calorimeter analysis, the thermal characteristics concluded that even though five PEs irrespective of sources could be categorized as PE, the plastics differed significantly in terms of melting enthalpies with varied Xc and η. The volumetric analysis of plastic modified mixtures conveyed that PE with Xc (<65%) and η value (<5594 Pa.sec at 165°C) could act as a replacement for binder and satisfy the volumetric requirements. PE with Xc (>65%) and η (>5594 Pa.sec at 165°C) resulted in reduced workability of the mixtures. Such plastics were identified to have filler tendency rather than a binding material in the asphalt mixtures. Finally, PE with Xc value of 65.56% at a dosage of 6% is found to be optimum for designing PE modified mixture, irrespective of source. Overall, the study recommends to address PE in terms of core properties such as Xc and η rather than source or supplier to reduce variability and better understand its suitability in asphalt mixtures.
59. Ibrahim Joel
MS in Chemical Engineering
Advisor: Gerard Capellades
Title: Rapid Development of Antisolvent Crystallization
Abstract: In the current pharmaceutical landscape, the industry is facing steep challenges with escalating development costs and risks, pushing the average cost of bringing new drugs to market to unprecedented heights. This situation is exacerbated by extensive resource consumption during laboratory trials, which are crucial for optimizing process conditions and developing effective scale-up strategies. Solution crystallization, a pivotal step in this process, plays a critical role in recovering high-quality products from their component systems. Addressing these issues, this work aims to introduce an automated framework for efficiently obtaining crystallization kinetic parameters—such as crystal nucleation and growth—and devising scalable strategies, thereby reducing the financial burden associated with the crystallization process development. To tackle these challenges, an innovative approach was employed to acquire the kinetic parameters of various active pharmaceutical ingredients (APIs) in different solvent systems through an automated batch crystallization workflow, initially at a small scale of 5ml. This systematic investigation of kinetic parameters under varying solvent compositions served as a foundation for identifying scalable trends and establishing a basis for scale-up implementation and comparison. Subsequently, a scale-up design for a selected API at a 300ml volume was executed, utilizing a Mixed Suspension Mixed Product Removal (MSMPR) anti-solvent crystallization process. This methodology underscores the significance of understanding the effects of crystallizer configuration, hydrodynamics, and system properties across scales, offering valuable insights for the characterization of nucleation and growth patterns for similar APIs in solution systems. The findings from this comprehensive workflow revealed that an increase in solvent composition leads to a reduction in growth kinetics across all scales, while nucleation kinetics demonstrated variability with supersaturation—a parameter influenced by the metastable zone at selected solvent compositions. This consistent trend, particularly evident in the decrease in mean crystal length during continuous anti-solvent crystallization, highlights the intricate relationship between solvent composition, supersaturation levels, and crystallization kinetics. These observations provide a robust framework for optimizing crystallization processes, enabling the pharmaceutical industry to streamline drug development and scale-up procedures, ultimately reducing costs and enhancing the efficiency of bringing new therapeutic solutions to market.
60. Shaini Aluthgun Hewage
Post-Doctoral Fellow
Advisor: Cheng Zhu
Title: Evaluation of EICP-Treated Soil Performance under Freeze-Thaw Cyclic Effect
Abstract: Soil stabilization is significant in pavement engineering as it ensures a durable pavement system. However, conventional soil improvement techniques are often costly, energy-intensive, and pose environmental risks. Moreover, stabilized soil poses a concern against freeze-thaw susceptibility. Therefore, this study investigates the environmentally friendly and cost-effective soil stabilization method called enzyme-induced calcite precipitation (EICP) using soybean-extracted enzymes to improve the clayey soil surface cracking against the freeze-thaw cycles. Thus, soil samples are treated with different EICP solutions, with combinations of four different cementation solutions ratios (0: 1: 2: 3) with five different enzyme solutions (0 g/l, 30 g/l, 60 g/l, 90 g/l, and 120 g/l). The study consists of two EICP treatment cycles, each subjected to five freeze-thaw cycles under controlled temperatures of -20℃ and 20℃, respectively, and each freezing and thawing lasted for 24 hours. The experimental analysis consisted of 2D and 3D image analysis techniques combined with evaluating water evaporation patterns. Results confirm that the higher concentrations of EICP solutions produced higher calcite precipitation leads, hindering the surface crack formation and freeze-thaw damage in the clay soil. 2D image analysis results revealed treated samples against reduced crack ratio, total length, average width, and fractal dimension, and 3D analysis revealed that increment in sample volume related to calcite precipitation, reduction in surface area, and increase in 3D fractal dimension caused higher surface roughness due to formation of calcite after the second treatment. Study data confirmed that EICP treatment enhanced clay soil's resistance to freeze-thaw cycles through effective calcium carbonate precipitation.
61. Mohit Chaudhary
PhD in Transportation (Civil) Engineering
Advisor: Yusef Mehta
Title: Impact of Mixing Equipment on Fatigue and Thermal Cracking Performance of Asphalt Mixtures
Abstract: The addition of fibers to asphalt mixtures has the potential to improve the cracking resistance of asphalt mixtures. However, the state (distribution) of fibers in the asphalt mix is a critical parameter in determining the performance enhancement. This study aims to evaluate the impact of fiber distribution on the laboratory performance of asphalt mixtures. This was achieved by comparing the laboratory fatigue and thermal cracking performance of Plant Mixed Lab Compacted (PMLC) and Lab Mixed Lab Compacted (LMLC) fiber reinforced mixtures. Four types of laboratory and plant mixtures (Unreinforced, Polyolefin/ Aramid fibers (PFA) at 0.05% dosage, Sasobit coated Aramid fibers (SCA) at 0.01% and 0.02% dosage) were produced by using the New Jersey Department of Transportation (NJDOT) 9.5M76 mix. The fatigue cracking resistance was evaluated by the ITS and SCB test whereas the disk shape compact tension test was employed to determine the thermal cracking resistance of the mixtures. The bucket mixer was found to yield maximum fiber distribution owing to which it was selected to produce LMLC samples. The results showed that the fatigue cracking performance was improved with the addition of SCA fibers into the mix; however, fiber reinforced mixes (PFA 0.05% and SCA 0.01%) showed higher fatigue damage tolerance except SCA 0.02% reinforced mix. In addition, fiber reinforcement, regardless of dosage and combination, showed improvements in low temperature (thermal) cracking performance. Furthermore, based on ranking analysis for selected performance indicator from each experiment, SCA 0.02% reinforced mix on average showed highest cracking resistance. The outcomes of this study suggests laboratory bucket mixing method as a representative of plant produced fiber reinforced mixtures with consistent performance results.
62. Anil Kumar Baditha
Postdoctoral research associate in Transportation engineering
Collaborators: Ayyaz Fareed
Advisor: Yusuf Mehta
Title: Performance Assessment of Microencapsulated Phase Change Materials with Low to High Thermoregulation Range in Asphalt Binder
Abstract: Asphalt pavements face significant challenges due to low temperature cracking and rutting caused by extreme temperature fluctuations and traffic loading. These issues result in higher maintenance costs and reduced service life of the pavements. To address this, researchers explored the use of Microencapsulated Phase Change Materials (MPCMs) to induce thermoregulation in asphalt pavements. However, the existing research focused on high-temperature performance of binders, highlighting the need of research on evaluating the low-temperature performance. Therefore, the study aims to evaluate the impact of incorporating MPCMs on low to high temperature performance of binders. Three types of MPCMs were incorporated into asphalt binder with melting points of 6°C (MPCM6D), 28°C (MPCM28D) and 37°C (MPCM37D) at varying dosages (5%, 10%, and 20%) using a low shear mixture. The thermoregulation property and performance of binders were studied. Differential scanning calorimeter analysis was conducted to verify thermoregulation properties and assess the survival of capsules during blending. The low temperature cracking resistance was evaluated by measuring creep stiffness and creep rate using Bending Beam Rheometer (BBR). The behavior within and outside MPCMs thermoregulation range was assessed by examining complex shear modulus (G*) change rate through temperature sweep test. The results showed that enthalpy change increased with increase in MPCMs dosage, indicating effective thermoregulation and capsule survival. Due to steady state test conditions, BBR could not able to capture the low temperature performance of MPCM binders. The temperature sweep test indicated that G* change rate was not constant, illustrating that near the melting points, MPCMs could thermoregulate stiffness of binder. In conclusion, outside the thermoregulation range, all MPCMs positively impacted rutting resistance while compromising fatigue and low-temperature cracking attributable to physical interaction of MPCMs with binder. Within the thermoregulation range, MPCM6D and MPCM 28D effectively enhanced low and intermediate temperature cracking resistance whereas MPCM37D enhanced rutting resistance.
63. Mohamad Keblawi
PhD in Biomedical Engineering
Advisor: Vince Beachley
Title: Effect of Laser Zone Drawing on the Mechanical Properties and Morphology of Preloaded Electrospun Polylactic Acid (PLA) Nanofibers
Abstract: Electrospinning is fabrication technique capable of creating fibers on the nanoscale . It has been employed in a variety of biomedical fields including tissue engineering, wound healing, drug delivery, biosensors, and many more. One of the main polymers that has been used in such applications is polylactic acid, which is due to its excellent biocompatibility and biodegradability. Moreover, it is a nontoxic polymer FDA approved for direct contact with biological fluids. In addition to its biological properties, PLA has desirable mechanical properties. Nanofiber post-drawing and processing plays an important role in improving their mechanical properties and morphology. One of the methods of post drawing fibers is zone drawing. It is done by applying a localized source of heat to a fiber segment. Laser zone drawing is when the source of heat is a laser. This study aims to explore the effect of laser zone drawing on the mechanical properties and morphology of electrospun PLA nanofibers.
64. Cristina Padovani
PhD in Molecular Cell Biology and Neuroscience
Advisor: Kingsley Yin
Title: Resolvin D2 rescues exhausted macrophages in a TLR2-dependent manner
Abstract: The early phase of sepsis is characterized by immune overactivation, where release of pro-inflammatory mediators may lead to multi-organ dysfunction. In the late phase of sepsis, there is paradoxical immunosuppression, where the host is susceptible to opportunistic infections. Anti-inflammatory agents may accelerate the host into immunosuppression, and few agents can reverse immunosuppression without causing further inflammation. Specialized Pro-resolving Mediators (SPMs) such as Resolvin D2 (RvD2) are endogenously produced fatty acids which have been reported to resolve infectious inflammation without being immunosuppressive; however, little work has been conducted to examine their effects on immunosuppression. To assess the effects of RvD2 on immunosuppression, we established a model of macrophage exhaustion using two lipopolysaccharide (LPS) treatments or “hits.” THP-1 monocyte-derived macrophages were first treated with RvD2 or saline vehicle for 1h. One LPS hit increased NF-κB activity 11-fold and TNF-α release 60-fold compared to unstimulated macrophages. RvD2 decreased LPS-induced NF-κB activity and TNF-α production but increased bacterial clearance of Pseudomonas aeruginosa. Two LPS hits reduced macrophage bacterial clearance of P. aeruginosa, and decreased macrophage NF-κB activity (45%) and TNF-α release (75%) compared to one LPS hit, demonstrating exhaustion. RvD2 increased NF-κB activity, TNF-α release, and bacterial clearance of P. aeruginosa following two LPS hits compared to saline controls. Inhibition of toll-like receptor 2 (TLR2) abolished RvD2-mediated changes in exhausted macrophages. In a mouse sepsis model, splenic macrophage response to exogenous LPS was reduced compared to sham controls and was restored by in vivo administration of RvD2, supporting the in vitro results. The results suggest that RvD2 modulates macrophage responses in vitro and in vivo, where it helps preserve cell activity during two-hit, LPS-mediated macrophage exhaustion. Our findings indicate that these actions are TLR2-dependent. Overall, our results provide evidence that RvD2 may be beneficial to attenuate immunosuppression in sepsis.
65. Quy Nguyen
PhD in Cell Biology and Neuroscience
Advisor: Jeremy Francis
Title: Over-expression of N-acetylaspartate synthase exacerbates pathological energetic deficit and accelerates cognitive decline in the 5xFAD mouse
Abstract: N-acetylaspartate (NAA) is an abundant central nervous system amino acid derivative that is tightly coupled to mitochondria and energy metabolism in neurons. A reduced NAA signature is a prominent early pathological biomarker in multiple neurodegenerative diseases and becomes progressively more pronounced as disease advances. Because NAA synthesis requires aspartate drawn directly from mitochondria, we argued that this process is in direct competition with oxidative phosphorylation for substrate and that sustained high levels of NAA synthesis would be incompatible with pathological energy crisis. We show here that over-expression of the rate-limiting NAA synthetic enzyme in the hippocampus of the 5x familial Alzheimer's disease (5xFAD) mouse results in an exaggerated pathological ATP deficit and accelerated cognitive decline. Over-expression of NAA synthase did not increase amyloid burden or result in cell loss but did significantly deplete mitochondrial aspartate and impair the ability of mitochondria to oxidize glutamate for adenosine triphosphate (ATP) synthesis. These results define NAA as a sink for energetic substrate and suggest initial pathological reductions in NAA are part of a response to energetic crisis designed to preserve substrate bioavailability for mitochondrial ATP synthesis.
66. Liza Guner
PhD in Biomedical Engineering
Advisor: Rachel Riley
Title: Engineering Lipid Nanoparticles for Delivery of RNA in Pediatric Acute Myeloid Leukemia
Abstract: Pediatric acute myeloid leukemia (AML) is the second most prevalent cancer in children [1]. Children diagnosed with this disease are faced with a 70% survival rate and a 25-35% chance of eventual relapse [1]. Current standard-of-care for pediatric AML includes chemotherapy and bone marrow transplantations [1]. While these therapies yield desirable results in many patients, some do not respond, their disease becomes resistant to further therapy, or the delivered dose is limited due to severe side effects. Recently, immunotherapies have shown promising results in clinical and pre-clinical testing for treating pediatric AML. However, long manufacturing times, expensive production, and severe adverse toxicities limit the widespread implementation of these therapies [2-3]. Therefore, there is a need for new therapeutics that are both effective and safer than current options. In this project, we are developing a nanoparticle-based therapy for gene regulation in AML. Towards this goal, we use lipid nanoparticles (LNPs) to deliver therapeutic nucleic acids to specific cells and tissues. LNPs have been tested both pre-clinically and clinically for a range of diseases and for vaccines, and they are FDA approved for several applications [4]. Thus, we have chosen to use LNPs in this project due to their translatability, efficacy, and safety in humans and animal models. We have evaluated LNPs to deliver luciferase mRNA to two pediatric AML cell lines. We showed that LNPs yield high luciferase mRNA delivery and protein translation to AML cells after 24 hours in a dose-dependent manner. We also demonstrated that LNPs have low toxicity to AML cells, indicating their safety for further study. Here, we use this LNP platform to deliver WT1 siRNA. WT1 is a gene that is often mutated in pediatric AML and causes increased cell proliferation [5] With this approach, we hypothesize that WT1 siRNA will silence WT1 to decrease AML proliferation and survival. Ultimately, we aim to demonstrate that LNPs can initiate robust gene regulation to halt AML progression and improve survival in patients.
67. Brittany Friedson
PhD in Molecular Cell Biology and Neuroscience
Advisor: Katrina Cooper
Title: Ubiquitin and Snx4 promote autophagy of translation initiation factor eIF4G1 under nitrogen starvation
Abstract: The ubiquitin proteasome system (UPS) and the autophagy-lysosomal pathway (ALP) are complex molecular machines that destroy misfolded proteins and damaged organelles to maintain homeostasis. Following stress, the regulated destruction of proteins and organelles is critical for cellular survival. The UPS and ALP were originally considered to be distinct pathways, but it is becoming more apparent that they are intricately linked through ubiquitin. However, the role of ubiquitin in selective autophagy pathways is not well understood. Here, we demonstrate in Saccharomyces cerevisiae that translation initiation factor eIF4G1 requires ubiquitin for autophagic degradation following nitrogen starvation (SD-N). We also found that the sorting nexin Snx4 promotes the degradation of eIF4G1. This is important as eI4G1 is a critical component of translation, and abnormal expression of eIF4G1 has been associated with cancers and neurodegenerative diseases. These data demonstrate a new role for ubiquitin in promoting autophagy of substrates which serve functions in protein synthesis.
68. Jibran Imtiaz
PhD
Advisor: Ronald Ellis
Title: Identifying co-factors for TRA-1 activator function
Abstract: Gli proteins are involved in cell fate determination, proliferation, and patterning in many species and are major effectors of Hedgehog (Hh) signaling. There are three Gli proteins in humans, and mutations or errors in their regulation lead to a variety of developmental disorders or cancer. However, the mechanisms by which they interact with co-factors are poorly understood. We are analyzing co-factors of Gli proteins using TRA-1 in Caenorhabditis nematodes. The TRA-1 zinc fingers are structurally like those of other Gli proteins, and TRA-1 can be cleaved like other Gli proteins to form a repressor. However, its function has changed during evolution — in nematodes, TRA-1 controls sexual fates and plays a central role in self-fertility, which makes it easy to assay mutant phenotypes. Furthermore, worms lack classical Hedgehog signaling, so study of nematode TRA-1 should reveal other types of regulation. Our lab has shown that full-length TRA-1 can work as an activator and promote spermatogenesis, and that the mutation cbr-tra-1(v48) disrupts this process and prevents spermatogenesis. We suspect that regulation of TRA-1 activator plays a major role in the evolution of hermaphrodite spermatogenesis in nematodes. Because v48 was isolated in a classical EMS mutagenesis, we recently made other activator mutations to confirm that all of its phenotypes were due solely to the alteration of TRA-1. Since TRA-1 activator is likely to interact with a diverse set of co-factors, whose activities might help determine whether specific targets are activated or repressed, we identified sites in TRA-1 where an OLLAS tag does not inactivate the protein and used anti-OLLAS antibodies to isolate TRA-1 complexes. We are now characterizing the products, and preparing to analyze them with mass spectrometry. While doing so, we hope to identify TRA-1 co-factors and learn how they regulate Gli activity.
69. Tamaraty Robinson
PhD in Molecular Cell Biology and Neuroscience
Collaborators: Ayesha Gurnani
Advisor: Katrina Cooper
Title: Cyclin C promotes TDP-43-mediated mitochondrial dysfunction and cell death.
Abstract: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease with no effective cure, and a life expectancy of 3-5 years after diagnosis. A hallmark of ALS is the aberrant cytoplasmic accumulation of TDP-43, a nuclear DNA/RNA binding protein, which results in the formation of toxic aggregates. Significantly, preventing mitochondrial fission reduces TDP-43 import and cell death, suggesting that mitochondrial dynamics contribute to TDP-43 pathobiology. However, the molecular mechanisms on how this is implemented remain elusive. Cyclin C is a new player in TDP-43-mediated cell death pathways. This non-canonical cyclin is a conserved member of the Cdk8 module (CKM) of the Mediator complex. Under physiological conditions, the CKM regulates the transcription of a wide range of stress response genes, partially mediated by cyclin C-Cdk8 kinase phosphorylation of transcription control factors. Following oxidate stress, cyclin C, but not Cdk8, translocates to the cytoplasm, where it binds to the mitochondrial fission GTPase DRP1. It is required for stress-induced mitochondrial fission and, by binding to BAX, promotes MOMP and cytochrome c release. Using an established yeast model of TDP-43 proteinopathies we determined that cyclin C contributes to TDP-43 toxicity. Here, the cytoplasmic accumulation of TDP-43 promotes cyclin C’s nuclear release, where it mediates TDP-43-triggered mitochondrial hyper-fission and cell death. This suggests that the second, stress-induced role of cyclin C contributes to TDP-43 pathobiology. Preliminary results using HEK293A cells suggest that this role is likely conserved. Current studies aim to dissect both the transcriptional and mitochondrial role cyclin C plays in TDP-43-mediated mitochondrial dysfunction. This includes determining if cyclin C promotes the cGAS-STING-induced cell death, which is triggered by the release of mtDNA in TDP-43 pathogenesis. As mitochondrial dysfunction plays a key role in ALS and other proteinopathies, these studies could provide therapeutic outlets to target the responsible molecular mechanisms.
70. Stacy Love
PhD in Computational and Integrative Biology
Advisor: Sebastian Vega
Title: Innovative DWIVA Peptide-functionalized Hydrogels for Targeted Long-bone Formation
Abstract: The incidence of osteoporosis, a prevalent chronic metabolic bone disease, is increasing with the aging population, leading to an increased risk of fragility fractures. While bisphosphonates mitigate bone loss and fracture risk, their systemic nature and low patient compliance pose significant challenges. Recombinant human bone morphogenetic protein-2 (BMP-2) provides a more focused therapeutic approach because of its crucial role in bone and cartilage formation. DWIVA, an epitope derived from BMP-2, can endow hydrogels with osteoinductive properties. This study explores the potential of self-forming DWIVA-functionalized hydrogels with encapsulated mesenchymal stem cells (MSCs)—when injected into the intramedullary canal of rat femurs—to induce localized trabecular bone growth. Notably, hydrogels functionalized with DWIVA peptides led to an increase in bone volume, trabecular thickness, and trabeculae count at the injection site in as little as four weeks. Additionally, the inclusion of MSCs led to an even higher development of mineralized bone. Histological analysis of decalcified femurs reveals that DWIVA- and MSC-containing hydrogel injections stimulate unmineralized bone tissue formation in as early as two weeks post-injection. Moreover, after four weeks, an increased count of bone-forming osteoblasts and bone-resorbing osteoclasts was observed at the injection site, suggesting that the newly formed bone is undergoing remodeling, a property innate to native bone. In summary, MSC-laden DWIVA-functionalized hydrogels rapidly induce targeted bone formation, presenting a promising avenue for promoting nascent bone development in sites prone to osteoporosis-related fragility fractures, such as the femur.
71. Victoria Wong Murray
DO student at Virtua
Collaborators: Courtney Liam
Advisor: Judith Lightfoot
Title: False Positive Syphilis Titer: Medication or Autoimmunity?
Abstract: Introduction: Syphilis screening, a common medical test in the US, is recommended annually in sexually active women younger than 25, annually for women older than 25, and annually for men(1). Standard tests include rapid reagin tests and Venereal Disease Research Laboratory tests, which react to membrane antigens of Treponema pallidum(2). Case reports of patients with autoimmune conditions have been described (3) but rarely considered in clinical practice. Additionally, patients may be underdiagnosed with autoimmune conditions with clinically relevant antibodies (4). Here, we describe one such case where a patient received delay in care prior to referral to our service. Case Presentation: A 52-year-old woman presented with chief complaint of lower extremity biopsy-proven leukocytoclastic vasculitis with joint pain, swelling, and new ulcers; with syphilis titer of 1:8 on RPR but denies sexual activity or use of antimicrobials within the last year. Current diagnoses include obsessive-compulsive disorder and antiphospholipid syndrome. Her medication history included a short, subtherapeutic dose of 100mg of minocycline; and prednisone, naproxen, famotidine, ibuprofen, olmesartan, amlodipine, hydrochlorothiazide, prednisone, pentoxifylline, fluvoxamine maleate, and albuterol. Physical exam demonstrated a lace-like rash and narrowing on upper and lower extremities with ulceration and substantial edema. Subsequently, she also demonstrated a substantial amount of oral candidiasis. Upon further testing, her eosinophil count was 0, CRP 3 mg/L, HIV negative, syphilis antibodies negative, and RPR remained positive. Her symptoms improved after discontinuation of fluvoxamine and prednisone initiation. Conclusion: Antiphospholipid syndrome, lymphocytoclastic vasculitis, and fluvoxamine may have contributed to this patient’s false positive RPR for syphilis, as well as a delay in treatment for her vasculitis of several months due to pursuit of syphilis workup and treatment. The prevalence of antiphospholipid syndrome has been estimated at 1/2000(4) and should be considered in the workup of patients presenting with high RPR titer and no clear exposure history.
72. Vanessa Pizutelli
DO/PhD, Molecular Cell Biology and Neuroscience
Advisor: Dimitri Pestov
Title: Investigating ribosomal RNA as a potential biomarker for cellular injury
Abstract: Ischemic injury causes an array of pathologies that impact the global population.
Ischemia/reperfusion injury (IRI) results from an initial restriction in blood flow to tissue followed by a sudden restoration of perfusion. This type of paradoxical injury is responsible for significant cellular death and contributes to diseases like myocardial infarction, acute kidney disease, ischemic stroke, and TBI. The diverse presentation and pathogenesis of TBI make it challenging to accurately assess the degree of trauma and predict the clinical outcome of patients. Biomarkers for TBI have been identified, but many have limitations. Thus, identifying biomarkers that can improve diagnostic accuracy and clinical outcomes would be a significant advancement for these patients. Ribosomal RNA (rRNA) is a long lived molecule that is altered by oxidative stress. In cell culture experiments, we have observed distinct patterns of rRNA fragments in cells exposed to oxidative stress conditions and after induced defects in metal homeostasis. Through Next Generation Sequencing (NGS), we have demonstrated that redox and iron homeostasis alterations can induce site specific breaks in rRNA in different cell types. Given that rRNAs are highly abundant molecules that carry a record of damaging events, exploring changes in rRNAs during IRI may provide valuable insights into the underlying mechanisms that contribute to this pathology. Experiments are in progress to recreate hypoxic and reoxygenation conditions in human neuronal cell lines to elucidate how these conditions directly affect rRNA integrity and if these changes produce distinct fragmentation patterns and single-nucleotide alterations.
73. Fayez Alruwaili
PhD in Biomedical Engineering
Advisor: Mohammad H. Abedin-Nasab
Title: Haptic Guidance Approach for the Realignment of Femur Fractures Using a Robot-Assisted Surgical System
Abstract: The reduction of femur fractures is a very tedious process and requires the manipulation of the femur segments in the 6-dimensional space. To mitigate these challenges, we aim to incorporate a haptic feedback approach that will guide the surgeons in aligning the femur segments while eliminating the challenges of unwanted manipulation and bone-bone collision. As guided by the patient's 3D femur model and the extent of malrotation and malalignment, we implement a Bézier curve-based approach to generate virtual fixtures given the control points generated by an optimized A* algorithm. The Bézier curve-based virtual fixture represents a guided path in the Robossis surgical robot 6-dimensional space, directing its end-effector through a sequence of desired poses while adhering to the optimized path provided by the A* algorithm. As the optimal path is determined, we provide the surgeon(s) with a haptic-guided path to align the bone fragments. Specifically, the surgeon manipulating the haptic controller will be guided to move only along the optimal path for bone alignment as defined via the virtual fixtures. We use the Robossis Surgical Simulator, as developed in previous work, to create a midshaft femur fracture and validate the developed haptic guided algorithm for the fracture realignment. The results show that the user, manipulating the haptic controller, was successfully able to align the femur fracture segments while adhering to the optimal path with a maximum deviation from the translation and rotation space of 3.0 (mm) and 1.5 (deg), respectively. As such, the result shows that the proposed method can provide an intuitive solution for surgeons to realign femur fractures using the robot-assisted surgical system while eliminating the challenges of unwanted manipulation and bone-bone collision.
74. James Kennedy
PhD in MCBN
Advisor: Ronald Ellis
Title: Evolution of fem-1 activity in Caenorhabditis
Abstract: Hermaphrodite sex determination is shared between the Caenorhabditis species C. elegans, C. briggsae, and C. tropicalis, but this trait is thought to have occurred independently. The core pathway that makes this determination shares large similarity in the Caenorhabditis genus among which are the FEM complex proteins: FEM-1, FEM-2, and FEM-3. These proteins were discovered in C. elegans where corresponding genes are necessary for male sex determination as evidenced by null mutants producing feminizing mutations in the soma and germline in both XX and XO animals. This phenotype is not shared in C. briggsae where fem-2 and fem-3 null mutants in both XX and XO animals are hermaphrodites. This difference suggests a divergence in the role of the FEM complex in these two species. The mutant strain of fem-1(v508) showed an identical phenotype to C. briggsae fem-2 and fem-3 null mutants. To place fem-1 in the sex determination pathway, double mutants of this gene with its direct upstream (tra-2) and downstream (tra-1) genes were produced. The expected results were received with tra-1(v181); fem-1(v508) mutants being XX males and tra-2(nm1); fem-1(v508) mutants being XO hermaphrodites. A null triple mutant of fem-2(nm27); fem-3(nm63) fem-1(v517) was produced which has an identical phenotype to individual null mutants. A complex relationship between the FEM proteins and germline development is suggested by oogenesis in tra-1; fem double mutants in C. elegans. This was replicated in C. briggsae by germline scoring of tra-1(v181) mutants with corresponding fem genes. A spermatogenesis to oogenesis switch was seen in these tra-1 males. The epistatic interactions of C. tropicalis between fem-1 and its upstream (tra-2) and downstream (tra-1) genes in the sex determination pathway. These null mutants (tra-1 and tra-2) are XX males. It is expected that the somatic and germline phenotypes of double mutants will show similarity to C. elegans.
75. Morgan Antisell
PhD in Biomedical Engineering
Collaborators: Hoi Yan Yu
Advisor: Sophia Orbach
Title: Predictive Modeling of Cytochrome P45 Regulation and Adverse Polypharmacy Reactions
Abstract: Cytochrome P450 (CYP) enzyme activity is the driving force of Phase I drug metabolism, modifying substances into metabolites that can be excreted from the body. This process is vital to limiting oxidative stress to prevent drugs from impairing homeostatic functions. Yet, increased ingestion of a substance can result in a build-up of metabolites that induce liver toxicity. There are no established methods to predict CYP-mediated toxicity for an individual patient. Enzyme activity is highly variable across individuals and patients are often prescribed multiple drugs that further modify CYP activity. Understanding these interactions is vital to prevent liver toxicity. We aim to attack this problem in two ways. Our first goal is to predict a patient’s basal CYP activity based on their respective transcriptomic regulation. Basal CYP regulation will be determined by correlating the RNA expression of transcription factor-related genes with the enzymatic activity of CYPs. Our second goal is to determine whether a patient will experience adverse reactions given a combination of drugs. Polypharmacy-induced adverse drug reactions will be predicted using clinical data and machine learning methods. This research is anticipated to impact the translation of transcriptomic data in clinical pharmacology practice, informing personalized prescription regimens to reduce the risk of adverse drug reactions.
76. Navya Sree Devaguptapu
MS in Biomedical Engineering
Advisor: Ying (Grace) Chen
Title: Hybrid Lipid-Gold Nanoparticles for Simultaneous Gene Therapy and Photothermal Therapy to Treat Pediatric Acute Myeloid Leukemia
Abstract: Many standard-of-care cancer therapies include a combination of chemotherapy, surgery, radiation, and, for leukemia, hematopoietic stem cell transplantation. However, these options are associated with severe side effects including suppressed immune function, thrombocytopenia, and neutropenia, among others. Long-term side effects include potential infertility and increased risk of secondary cancers. Similarly, stem cell transplantation leads to complications like graft-versus-host disease (GVHD). Thus, there is a pressing need for innovative therapeutic approaches to enhance `treatment outcomes in cancer. We have developed a novel, hybrid drug delivery platform to treat cancers, with a specialized focus on pediatric AML and ovarian cancer. Our platform is comprised of a nanoshell core and ionizable lipid coating. Nanoshells are made of silica cores and thin gold shells and are highly efficient heat transducers to enable photothermal therapy (PTT). In PTT, near-infrared laser light activates nanoshells embedded in tumors, producing heat. Alternatively, the coated ionizable lipids are efficient for intracellular nucleic acid delivery, including small interfering RNA or messenger RNA, to modulate gene expression. Thus, we hypothesized that these lipid-gold hybrid nanoparticles (LGNPs) could enable simultaneous gene therapy through the lipid exterior and PTT from the nanoshell core. We synthesized the LGNPs through a controlled self-assembly process, incorporating a lipid layer on the nanoshells with a poly(ethylene) glycol (PEG) linker. We encapsulated luciferase mRNA into the lipid exterior to enable simple detection of mRNA translation using a plate reader. Characterization revealed that the hydrodynamic diameter of the nanoshells was 169.9 nm ± 8 nm, while LGNPs exhibited a size range between 230nm to 306nm, depending on the percentage of PEG used. The encapsulation efficiency of mRNA was 72%. We treated two AML cell lines with LGNPs or controls to assess their mRNA delivery efficiency, which yielded a 300-fold increase in luminescence in Kasumi-1 cells (AML line) and a 2700-fold increase in luminescence in OVCAR-3 cells (ovarian cancer) when compared to PBS-treated wells and cells treated with PEG-coated nanoshells with no coating. These studies demonstrate that LGNPs enable mRNA delivery to cancer cells. Currently, I am evaluating the PTT efficiency of the LGNPs in both cell lines. Ultimately, we aim to introduce a multifunctional, hybrid drug delivery platform that combines PTT with efficient mRNA delivery, offering more effective and safer options compared to currently used therapeutics.
77. Emily Kopchick
PhD in Biomedical Engineering
Advisor: Ying Chen
Title: Enhanced Vascular Integration: A Biodegradable Elastomer-Based Arterial Graft Fabricated with Precision MEW Printing for Improved Functional Performance
Abstract: Cardiovascular disease is the leading cause of death in the United States. Prosthetic vascular grafts are commonly used to replace diseased veins or arteries. Current vascular grafts, primarily Gore-Tex ® and Dacron ®, don't integrate well with the host and have poor biocompatibility in small-diameter vessels ( < 6mm). Biomaterials with proper viscoelasticity, compliance, and good biocompatibility may enable their use in small blood vessels. In response to this need, our project focuses on the development of novel metal-ligand coordinated biodegradable elastomers. These materials are designed to offer a broad range of mechanical properties and bioactivities, making them suitable for use in the fabrication of small-diameter vascular grafts. Our approach leverages the melting electrowriting method to create grafts that not only meet the mechanical demands of blood vessel replacement but also support cellular integration and tissue regeneration. To assess the efficacy and biocompatibility of our newly developed grafts, we will conduct a comprehensive series of in vitro and in vivo experiments. These studies will evaluate several critical factors, including the mechanical properties of the grafts, their biocompatibility, the extent of cell infiltration, the rate of polymer degradation and tissue regeneration, and the process of host remodeling. Through this research, we aim to introduce a promising alternative to current vascular graft materials, with the potential to significantly improve outcomes for patients with cardiovascular diseases.
78. Narangerel Gantumur
PhD in BME
Advisor: Ying (Chen) Grace
Title: A Novel Electroconductive & Regenerative Cardiopatch: Harnessing Zebrafish ECM with 3D Printing for Enhanced Myocardial Repair
Abstract: Myocardial infarction (MI), commonly known as a heart attack, results from the interruption of blood supply to the heart, causing irreversible damage to the cardiac muscle due to the limited regenerative capability of human myocardium. Our present research introduces a novel cardiopatch scaffold fabricated using Stereolithography (SLA) 3D printing technology, aimed at improving cardiac repair post-myocardial infarction. Inspired by the high myocardial regenerative capacity of zebrafish, our cardiopatch incorporates zebrafish cardiac extracellular matrix (zECM) to promote cardiomyocyte proliferation and cardiac regeneration. The electroconductive scaffold, made of poly(ethylene glycol) diacrylate (PEGSDA) interlaced with a bio-ionic liquid (Bio-IL), adheres to cardiac tissues via electrostatic forces and covalent bonding. These interactions ensure close contact with the myocardium, which is crucial for efficient electrical signal transmission and mechanical support during the healing process. The zECM component of the cardiopatch accelerates myocardial regeneration, aligning the degradation rate of the scaffold with the regenerative process of the tissue. Our approach not only offers a promising solution for heart repair after MI but also suggests a versatile platform for tissue engineering that can be tailored for other organs by altering the ECM source.
79. Erin Wannen
PhD in Molecular Cell Biology and Neuroscience
Advisor: Jessica Loweth
Title: Investigating the Role of Ovarian Hormones in Cue-Induced Cocaine Seeking
Abstract: Cues associated with cocaine use are one of the most common relapse triggers, and understanding what promotes cue-induced cocaine craving and relapse is a critical question in the field. Human studies have shown that these measures are impacted by fluctuations in hormone levels, as higher levels of estradiol promote cue-induced cocaine craving in women while higher levels of progesterone reduce craving in both sexes. Enhanced or incubated cue-induced cocaine seeking or craving also changes across the rodent reproductive (estrous) cycle as levels of estradiol and progesterone fluctuate. However, how gonadal hormones impact cocaine craving and relapse vulnerability in both sexes remains unclear. A thorough understanding of the intersection between hormonal and neuronal mechanisms in relapse vulnerability is critical for developing targeted treatment strategies to effectively reduce craving and promote abstinence in individuals with cocaine use disorder. To begin to investigate this, we conducted studies in both intact, naturally cycling and hormonally depleted (ovariectomized) rats. We focused on the basolateral amygdala (BLA), a sexually dimorphic brain region known to play a critical role in cue-induced cocaine seeking. Interestingly, we found an increase in both cue-induced cocaine seeking behavior and BLA excitatory synaptic transmission in females in the estrus stage of the cycle, when ovulation occurs, compared to both females in other cycle stages and males. Our findings indicate that these effects in females are estradiol-dependent. Additional biochemical studies have identified an interaction between cocaine exposure and ovarian hormone fluctuations on BLA glutamate receptor surface expression. Together these studies will significantly advance our understanding of the mechanisms underlying persistent cue-induced cocaine seeking and relapse vulnerability in both sexes.
80. Haven Predale
PhD in Neuroscience
Advisor: Barry Waterhouse
Title: Organizational Features and Functional Implications of the Locus Coeruleus-Norepinephrine Projection to Motor Centers of the Rodent Brain
Abstract: The brainstem nucleus locus coeruleus (LC) projects broadly throughout the forebrain, brainstem, cerebellum, and spinal cord and is a major source for release of the small molecule transmitter norepinephrine (NE) in these areas. While we know much about the organization of the LC-NE system with respect to sensory and cognitive circuitries and the impact of LC output on sensory guided behaviors and executive function, much less is known about the role of the LC-NE pathway in motor network operations and movement control. As a starting point for closing this gap in understanding, we are using the intersectional recombinase-based viral-genetic strategy TrAC (Tracing Axon Collaterals) to characterize LC-NE projections to motor control centers of the mouse brain. This technique allows us to not only map the distribution of LC-NE axons to target regions of the mouse brain, but also to examine the distribution of their cell bodies within the LC and their dendritic fields within the peri-coerulear space. Initial results indicate that there exists a dense distribution of cells that send axons to target regions of the cerebellum, i.e. the deep cerebellar nuclei and cerebellar cortex. The deep cerebellar nuclei receive input from a large number of bilaterally distributed LC neurons. Lobules in the anterior cerebellum and posterior cerebellum also receive input from bilaterally distributed LC cells, but these cells are less numerous and more scattered than those projecting to the deep cerebellar nuclei. These results contrast with the scattered and predominantly ipsilateral (95%) distribution of the NE-containing cells that project from LC to cerebral cortex including the primary motor cortex. The overarching goal of this work is to determine the distribution of motor projection neurons within LC, visualize their dendritic fields within the peri-coerulear space, and characterize their electrophysiological properties. The expectation is that this information will establish a foundation for future studies aimed at elucidating the role of the LC-NE system in motor control.
81. Camila Vardar
PhD in Biomedical Engineering
Collaborators: Giavanna Trojan
Advisor: Mark Byrne
Title: New Prophylactic Treatment for Posterior Capsular Opacification: Assessment of the Dose-Response Relationship of Novel Nanocarriers in a In-Situ Forming Sustained Release Platform
Abstract: Background: Cataracts, characterized by a clouding of the lens of the eye, are the second leading cause of blindness worldwide. Posterior capsular opacification (PCO) is the most common postoperative complication of cataract surgery. PCO develops when cells migrate into the typically acellular lens capsular bag, hyper-proliferate and transdifferentiate into contractile myofibroblasts, which lead to wrinkling in the lens capsule. Current treatment strategies are insufficient and pose several adverse effects; therefore, a prophylactic treatment strategy delivered during cataract surgery is a considerable unmet need. Methods: Thermo-responsive injectable poly(D,L-lactic-co-glycolic acid)-b-poly(ethylene glycol)-bpoly(D,L-lactic-co-glycolic acid) (PLGA-PEG-PLGA) hydrogels were loaded with either a low or a high dose of doxorubicin- loaded, antibody-targeted nanocarriers (G8:3DNA:Dox). Human rhabdomyosarcoma (RD) cells, selected for their expression of PCO marker brain-specific angiogenesis inhibitor 1 (BAI1), were kept under dynamic media flow and received either a low or high dose of nanocarriers. Cells were fixed and stained at predetermined time points to evaluate targeted depletion of BAI1+ cells. Results: The lower dose of nanocarriers in hydrogel depleted BAI1+ cells more slowly than the higher dose, while both reached over 90% BAI1+ cellular nonviability after 28 days. The relative abundance of BAI1+ cells in the total population for both treatment groups was significantly lower than that of the control group. Conclusions: Controlled drug release of the lower dose of nanocarriers can achieve therapeutically relevant effects in the prevention of PCO, potentially decreasing the side effects associated with delivery of cytotoxic drugs. Given the observed decrease in BAI1+ cells, it is hypothesized that targeted depletion over a long time can help downregulate further myofibroblast differentiation on the lens capsule, thereby preventing the development of PCO.
82. Rachel Young
PhD in Biomedical Engineering
Advisor: Rachel Riley
Title: Lipid Nanoparticle Delivery of Placental Growth Factor (PlGF) mRNA as a Potential Therapeutic for Pregnancy-Related Disease
Abstract: Lipid nanoparticles (LNPs) have gained attention as drug delivery platforms for vaccination against COVID-19 and protein replacement therapies for other diseases. Developing LNPs that can safely deliver nucleic acids to the placenta would enable the treatment of prenatal diseases such as preeclampsia (PE), intrauterine growth restriction, gestational diabetes, and others. PE is a complex pregnancy condition caused by improper placental development, leading to an imbalance of angiogenic and anti-angiogenic factors. During PE, placental growth factor (PlGF) is reduced in maternal serum, causing a restriction of blood flow to the placenta compared to healthy pregnancies. Here, we develop LNPs to deliver PlGF mRNA to promote its production and secretion from trophoblasts in the placenta as a potential therapeutic for PE. Benefits of LNPs include improved nucleic acid stability, circulation time, cell uptake, and tissue specificity compared to drugs without a carrier. Altering the molar ratios of each component in LNPs influences tissue- and cell-specificity, and we hypothesized that LNP design could be manipulated to enable delivery to the placenta. We conducted a design of experiments to explore how LNP composition, including the type and molar ratio of each component, drives trophoblast and placental delivery. We found a specific combination of ionizable lipid and phospholipid in LNPs yields high transfection efficiency in vitro. We evaluated therapeutic placental growth factor (PlGF) mRNA delivery to trophoblasts using our top-performing LNP design, which resulted in a 19-fold increase in PlGF compared to basal levels. In pregnant mice, our LNPs induced PlGF synthesis in the placenta and secretion into the serum with no toxicity to both the pregnant mice and fetuses. This exploration of LNP-mediated delivery of mRNA demonstrates successful drug delivery to trophoblasts in vitro and the placenta in vivo for future applications in treating PE and other placental disorders.
83. Antonio Abbondandolo
PhD in Biomedical Engineering
Advisor: Erik Brewer
Title: Assessing the Degradation Profiles of a Thermoresponsive Polyvinyl Alcohol (PVA)‐Based Hydrogel for Biomedical Applications
Abstract: Primary challenges associated with the design and success of polymeric biomedical devices are generally related to the control of the biomaterial in terms of degradability characteristics, sufficient processability characteristics, and required mechanical strength that may be altered during sterilization or manufacturing procedures. Polyvinyl alcohol‐based thermoresponsive biomaterials provide a distinct advantage for biomedical applications as their physiochemical properties can be easily modified according to their desired use. In this work, we evaluated the thermal degradation characteristics of a polyvinyl alcohol (PVA)/polyethylene glycol (PEG)/polyvinylpyrrolidone (PVP) hydrogel that undergoes a steam sterilization autoclave cycle at 121°C to induce fluid‐like behavior. FTIR was used to characterize the evolution of the area of the carbonyl region between 1800 and 1525 cm−1. The carbonyl area increased at temperatures beyond 121°C which were used to accelerate the onset of degradation during both thermal oxidation and pyrolysis. The change in the carbonyl region was shown to correlate with respect to both temperature and time of exposure. The carbonyl region increased significantly in the presence of oxygen at temperatures above 150°C. Despite showing signs of thermal degradation at temperatures exceeding 150°C, our biomaterial was shown to be stable at 121°C during thermal degradation testing. Furthermore, bulk property analysis showed the hydrogel's mechanical and swelling properties were preserved even after being subject to multiple autoclave cycles beyond what would be experienced during a sterilization or clinical procedure.
84. Umu Jalloh
PhD in Biomedical Engineering
Advisor: Sebastian Vega
Title: Synthesis and Photopatterning of Synthetic Thiol-Norbornene Hydrogels
Abstract: Hydrogels are a class of soft biomaterials and are the material of choice for a myriad of biomedical applications due to their biocompatibility and highly tunable mechanical and biochemical properties. Specifically, light-mediated thiol-norbornene click reactions between norbornene-modified macromers and di-thiolated crosslinkers can be used to form base hydrogels amenable to spatial biochemical modifications via subsequent light reactions between pendant norbornenes in the hydrogel network and thiolated peptides. Macromers derived from natural sources (e.g., hyaluronic acid, gelatin, alginate) can cause off-target cell signaling, and this has motivated the use of synthetic macromers such as poly(ethylene glycol) (PEG). In this study, commercially available 8-arm norbornene-modified PEG (PEG-Nor) macromers were reacted with di-thiolated crosslinkers (dithiothreitol, DTT) to form synthetic hydrogels. By varying PEG-Nor weight percent or DTT concentration, hydrogels with a stiffness range of 3.3 kPa to 31.3 kPa were formed. Pendant norbornene groups in these hydrogels were used for secondary reactions to either increase hydrogel stiffness (by reacting with DTT) or to tether mono-thiolated peptides to the hydrogel network. Peptide functionalization does not affect bulk hydrogel mechanics, and this confirms that mechanical and biochemical signals can be independently controlled. Using photomasks, thiolated peptides can also be photopatterned onto base hydrogels, and mesenchymal stem cells (MSCs) attach and spread on RGD-functionalized PEG-Nor hydrogels. MSCs encapsulated in PEG-Nor hydrogels are also highly viable, demonstrating the ability for this platform to form biocompatible hydrogels for 2D and 3D cell culture with user-defined mechanical and biochemical properties.
85. Samuel Hofbauer
MD/PhD Biomedical Engineering
Advisor: Rachel Riley
Title: Lipid Nanoparticles for mRNA Delivery to Trophoblasts for Local Immunomodulation
Abstract: Preeclampsia is the most common pregnancy-related disease affecting 2-8% of pregnancies. It is characterized by the development of hypertension and proteinuria after 20 weeks of gestation. The only curative treatment for preeclampsia is preterm delivery, which can increase morbidity and mortality depending on the age of gestation. Thus, it is critical to develop new ways to treat and prevent preeclampsia to enable healthy pregnancy. An underlying cause of preeclampsia is abnormal immune activity in the decidua early in pregnancy. Specifically, inflammatory M1 macrophages predominate in the decidua contributing to poor spiral artery invasion and remodeling leading to hypertension. In this project, we aim to locally modulate placental immune activity to promote proper placentation using lipid nanoparticles (LNPs). LNPs are comprised of ionizable lipids, phospholipids, polyethylene glycol (PEG), cholesterol, and nucleic acids such as messenger RNA (mRNA). The LNPs protect the encapsulated mRNA from premature degradation and promote its delivery to target cells. LNPs have been successfully used to treat several diseases, most notably in the Pfizer and Moderna coronavirus vaccines. We recently developed LNPs to deliver therapeutic mRNA to the placenta with high efficiency and safety to both pregnant mice and fetuses. Here, we are using these LNPs to deliver cytokine mRNA to trophoblasts, the main cell type in the placenta, to locally modulate immune activity through macrophage polarization. Herein, we developed LNPs to deliver IL4 and IL13 mRNA to trophoblasts to induce secretion of these cytokines and polarize tissue-resident macrophages to a tissue remodeling M2 phenotype. LNPs encapsulating IL4 mRNA (IL4-LNPs) and IL13 mRNA (IL13-LNPs) were delivered to two trophoblast cell lines, BeWo cells and HTR8/svNEO cells. High levels of cytokines were secreted from both cell lines when treated with IL4 and IL13 LNPs as assessed by ELISA. The cytokine containing media from LNP-treated BeWo cells was then used to culture patient derived monocytes in vitro. After 48 hrs, monocytes were assessed for polarization by flow cytometry, which yielded up to a 232% increase in CD209 expression on macrophages cultured in IL4/IL13 conditioned media compared to controls. In addition, we found that macrophages cultured in IL4/IL13 conditioned media secrete significantly more IL10 than control groups. This demonstrates that LNP treated trophoblasts can secrete cytokines to control macrophage activity. In the future, we envision our technology to enable local immune modulation to promote healthy placentation and prevent preeclampsia onset in high-risk patients.
86. Matthias Recktenwald
PhD in Biomedical Engineering
Advisor: Sebastian Vega
Title: Design of Extracellular Peptide-Ligand Dimerization Actuator Receptors for Programming Cell Behavior
Abstract: Advances in synthetic biology have brought about the ability to program mammalian cells with transmembrane receptors that respond to soluble and cell-laden ligands; however, there is limited research investigating synthetic receptors capable of responding to artificial and material-laden ligands. Here we demonstrate the rational design, development, and high throughput screening of synthetic de novo extracellular peptide epitope tag-responsive monobody receptors. Receptors specific to orthogonally designed peptide ligands were screened using a novel Extracellular Peptide-ligand Dimerization Actuator (EPDA) cell-surface receptor which reports the dimerization of two EPDA receptor halves. Internally, EPDA receptors utilize a recently published phosphorylation dependent push-pull post translational circuit mechanism along with easily quantifiable split fluorescence molecules. This novel investigational platform is orthogonal to endogenous pathways at the ligand, receptor, and intracellular levels giving researchers the ability to study a wide range of pathways and applications with minimal optimization. Once effective EPDA receptors were screened and optimized, they were used to show the unique potential of peptide ligands to be used in biomaterials research. Towards this, norbornene-modified hyaluronic acid hydrogels were functionalized with stimulatory peptide ligands. This work also looks at the first of its kind receptor which inhibits input signaling at the post-translational level in response to inhibitory extracellular peptide ligands. This is accomplished using a phosphatase domain attached to an additional epitope tag specific receptor to deactivate the stimulatory signal. Ongoing work involves the use of this platform to reconstitute a split dead Cas9 molecule that endows cells with the ability to synthesize and release therapeutically relevant cytokines and extracellular matrix-modifying molecules. This EPDA receptor platform enables mammalian cells to communicate with peptide-ligands and opens exciting avenues of research including the development of ‘living’ materials and synthetic autocrine signaling for regulating therapeutic outputs during cell therapy.
87. Shahab Edalatian Zakeri
PhD in Biomedical Engineering
Advisor: Patrick Hwang
Title: Translational Bioengineered Therapeutics for Diabetes Complications
Abstract: Diabetes affects 11.3% of the U.S. population and causes numerous complications. Diabetic foot ulcer (DFU) is a major complication occurring in 15% of diabetics signified by difficult-to-heal, often infected wounds as diabetes affects all aspects of a normal healing process. Current treatments only aim to target one or a limited number of factors in healing process with only 25% of DFUs healing within 8-12 weeks. Our design is a layered, multi-targeting patch including extracellular matrix-mimicking peptide amphiphiles (PAs), releasing nitric oxide (NO) with antimicrobial, angiogenic, and anti-inflammatory effects. Moreover, patch includes conductive fiber sheets designed to tunably localize energy loss of plugged-in electronics or triboelectric charging of walking motion into the wound area without requiring circuitry, wires, or batteries to promote cell activity. First, optimal electric stimulation parameters in diabetic conditions will be determined in cells involved in wound healing. Next, several polymers will be electrospun, silver-coated, and tested for optimal conductivity. NO will be charged to NO-donating sequence of PAs synthesized using solid-phase synthesis. NO release will be tested using Griess assay. Wound healing effect of the patch will be tested in diabetic rat models. Another complication of diabetes is hemodialysis due to end-stage renal disease. For hemodialysis vascular access, an arteriovenous fistula is often surgically created but frequently fails due to improper vessel dilation and neointimal hyperplasia requiring re-surgery. To address this, we will use a biocompatible, biodegradable, carbohydrate-based hydrogel loaded with sildenafil, a vasodilator, for perivascular, sustained-release delivery. Hydrogel will be fabricated using backbone-modified guar gum and crosslinked gelatin offering sustained release. The release kinetics, efficacy, and safety of the hydrogel will be evaluated and optimized in vitro in venous smooth muscle cells and then in vivo in a rat model of the fistula. These novel bioengineered therapeutics have translational capability for addressing persisting challenges of diabetes.
88. Enosh Lim
PhD in Biomedical Engineering
Collaborators: Antonia DeBastiani
Advisor: Moghimi Mohammad
Title: Vibrational Strength of Piezoelectric Array in Flexible Substrates for Conductive Hearing Aids
Abstract: Flexible hearing aids can benefit from piezoelectric actuators to generate vibrations on epidermis layer of skin behind the ear and noninvasively bypass conductive hearing loss. However, the major challenge is to generate a strong level of vibrations on the surface of skin that can reach cochlea with thin and low-power actuators. Lead zirconium titanate has a high piezoelectric constant and can generate vibrations with elevated levels of force and acceleration. In this paper, we assembled arrays of unimorph piezoelectric actuators composed of lead zirconium titanate to increase the vibration level and overcome damping in flexible substrate, skin, and bone. Finite element analysis was conducted to study the vibrations from a single actuator as well as an array of actuators. Also, the experimental data showed that an array of two actuators with adjusted phase increased the velocity of vibrations by 18 dB at 9 kHz compared to a single actuator on a flat aluminum foundation.
89. Myranda Sims
PhD in Biomedical Engineering
Advisor: Sebastian Vega
Title: Non-Union Bone Fracture Healing with BMP-2 Wrist Epitopes in HANor Hydrogels
Abstract: While most arm and leg bone fractures heal after medical intervention, about 10% fail to heal (non-unions), affecting over 100,000 Americans each year. Current techniques involve a second surgery to exchange orthopedic hardware (e.g., plates, screws) which stabilizes the initial fracture and addresses issues at the fracture site. BMP-2 (bone morphogenetic protein-2) is an FDA-approved protein that induces nuclear translocation of runt-related transcription factor 2 (Runx2), which leads to downstream osteogenesis. Although highly osteoinductive, BMP-2 in its delicate nature is clinically administered at very high concentrations that leads to unwanted side effects including ectopic bone formation and inflammation at the fracture site. BMP-2 has two bone-producing peptide domains, DWIVA and KIPKA, and our lab recently developed two different schemes to form hydrogels with BMP-2 peptides. To study the effects of DWIVA and KIPKA peptides on BMP-2 signaling, MSCs are encapsulated in photopolymerizable hydrogels that require light to form (Scheme 1) or are encapsulated in self-forming hydrogels that can be injected at the fracture site (Scheme 2). Using these two schemes, the MSCs are exposed to varying concentrations of DWIVA or KIPKA (0, 2, or 4 mM) or DWIVA + KIPKA (1:1 stoichiometric ratio, 2, or 4 mM) peptides, and the expression of BMP-2 related biomarkers during different stages of osteogenesis are being investigated. Yes-associated protein (YAP) signaling also favors MSC bone differentiation, and the effects of YAP signaling on BMP-2 peptide-induced osteogenesis are also under study. Ongoing work includes using a preclinical rat femur segmental defect model to investigate the efficacy of our BMP-2 peptide hydrogels in bridging bone gaps unable to naturally heal, and to study the pathways associated with new bone formation. Findings from this study will pave the way for creating novel interventions to treat fractures including non-unions.
90. Dipon Roy
PhD in Biomedical Engineering
Advisor: Mary Staehle
Title: Characterizing Brain Tumor Heterogeneity from scRNA-seq analysis of Gliosarcoma and Glioblastoma in CNS Neoplasms
Abstract: Gliosarcoma stands as a relatively rare entity within the realm of central nervous system tumors, distinguished by its unique composition comprising both glioblastoma multiforme and a sarcomatous element. While clinical management often treats gliosarcoma akin to glioblastoma, there exists a spectrum of opinions regarding their clinical aggressiveness, cellular lineage, and prognostic outlook in comparison to glioblastoma, with conflicting reports clouding the overall understanding. The complex landscape of tumor heterogeneity, primarily manifesting within individual tumors, poses a significant challenge to the development and implementation of personalized cancer therapy strategies. Advancements in molecular biology techniques, notably RNA-seq expression analysis, facilitate quantitative measurements of gene expression levels within cells. Leveraging single-cell RNA sequencing data provides a comprehensive glimpse into the nuanced differences in heterogeneity between low-grade gliomas, such as oligodendroglioma and astrocytoma, and high-grade counterparts, including glioblastoma and gliosarcoma. We also discuss how contemporary deep learning techniques show promise in identifying differences between the evolutionary trajectory and heterogeneity of infiltrated immune cells and cancer cells, as well as offering information on the makeup and function of each cell group in the inflammatory tumor microenvironment. These techniques not only offer insights into the composition and function of distinct cellular populations within the inflammatory tumor microenvironment but also hold potential in enhancing our understanding of their roles in disease progression. In summary, the integration of supervised classifiers with unsupervised techniques is paramount in elevating the precision of heterogeneity analysis, thereby broadening its applicability in guiding the longitudinal progression of therapy. This synergy of methodologies underscores the imperative need for personalized approaches in unraveling the intricate heterogeneity landscape of gliomas and paving the way for more effective therapeutic interventions.
91. Evan Hutt
PhD in Biomedical Engineering
Advisor: Peter Galie
Title: Engineered Cells to Sense and Respond to TGF-B
Abstract: Transforming Growth Factor Beta (TGF-b) signaling plays a crucial role in fibroblast mechanobiology, specifically the transition to a myofibroblast phenotype caused by increased extracellular matrix stiffness. Synthetic receptors provide an approach to alter the positive feedback loop caused by mechanics and TGF-b. Here, we introduce a synthetic post-translational circuit designed to enable cells to sense and respond to TGF-b. Our approach involves functionalizing transmembrane receptors with a TGF-b-specific single-chain variable fragment (scFv), fused to a transmembrane domain, and either an intracellular leucine zipper or kinase active domain. Complementing this, the circuit includes a reciprocal leucine zipper linked to a substrate, and an SH2 domain primed to selectively bind the phosphorylated substrate. Upon TGF-b stimulation, receptor dimerization occurs, facilitating the proximity of the kinase to the substrate, thereby promoting phosphorylation and subsequent SH2-substrate binding. Interaction of the phosphorylated substrate and SH2 domain, and therefore optimization and characterization of the circuit, can be studied through evaluation of the reconstitution of split mNeonGreen fluorescent proteins tethered to the substrate and SH2 domains. Extracellular and intracellular receptor linker length, TGF-b dose, time of dose, HEK native TGF-b autocrine signaling were considerations within optimization of the system, evaluated by split mNeonGreen reconstitution and extracellular surface expression by HA/Flag tagged receptors and antibodies. Future directions of this work lie primarily within the replacement of split mNeonGreen molecules with proteins of interest to induce an anti-fibrotic output in response to the pro-fibrotic TGF-b signal. For example, replacing the split fluorescent proteins with split dCas9 halves can yield anti-fibrotic molecule factory cells that secrete anti-fibrotic cytokines following delivery to TGF-b rich fibrotic environments. Alternatively, induction of native signaling proteins ALK1 and BMPR2 in fibroblasts may induce phosphorylation of native Smad1/5/8 that mitigate myofibroblast differentiation. Validation of either approach will be achieved by demonstrating decreased levels of a-SMA in fibroblasts in hydrogels with magnetically tuned mechanical properties.
92. Daniel Ball
MS in Biomedical Engineering
Advisor: Sebastian Vega
Title: Injectable Hydrogels that can Measure Radiation at Body Temperature
Abstract: Hydrogel-based radiation dosimeters are used to calibrate and validate radiation delivered by linear accelerators used in radiotherapy. Specifically, Fricke hydrogel-based dosimeters containing ferrous ion complexes oxidize upon exposure to radiation, leading to a change in optical density that can be measured via a color change in a photometric reagent. While gelatin-based Fricke hydrogels are routinely used to measure radiation, these hydrogels are unstable at body temperature and it is currently not possible to noninvasively measure radiation dose inside a patient. This study reports the synthesis and characterization of self-forming hydrogels containing Fricke components that are stable at body temperature. The effects of varying individual Fricke hydrogel components on the sensitivity (measured by change in optical density) to radiation dose were systematically studied. Self-forming hydrogels were prepared using xylenol orange (XO) in the range of 0.05 to 0.5 mM, ferrous ammonium sulfate (Mohr’s salt) in the range of 0.1 to 1 mM, and sulfuric acid (H2SO4) in the range of 0 to 100 mM. The minimum concentration of Fricke components to create self-forming hydrogels that are sensitive to radiation dose (0 to ~40 Gy) at room and body temperature was found to be XO (0.2 mM), H2SO4, (25 mM) and Mohr’s salt (0.5 mM). To assess self-forming hydrogel biocompatibility, human mesenchymal stem cells (MSCs) cultured in medium were exposed to cylindrical hydrogels containing Fricke components, and MSCs co-cultured with self-forming hydrogels containing the optimized formulation remained highly viable. To demonstrate the ability to measure radiation spatially, radiation beams of high (~40 Gy) and low (~20 Gy) doses were used to pattern a hydrogel with “V” (for Vega) and “L” (for Lab), respectively, resulting in distinct differences in optical density. Plans for a preclinical study using a rodent tumor model are underway, bringing this technology one step closer to clinical practice.
93. Nicole Hinds
PhD in Molecular and Cellular Biomedical Neuroscience
Advisor: Daniel Manvich
Collaborator(s): Ireneusz D. Wojtas, Desta M. Pulley, Stephany J. McDonald, Samantha de Guzman, Nicole E. Hubbard, Colin M. Kulick-Soper, Jessica J. Debski, Bianca Patel, Colton D. Spencer, Sara M. Hayden
Title: Activation of a neuronal cluster within the rostroventral periaqueductal gray is positively correlated with cocaine-seeking behavior in the rat
Abstract: Cocaine Use Disorder persists as a major public health threat and is characterized by a high risk for relapse, yet there are currently no FDA-approved pharmacotherapeutics available for its treatment. Stressors are known to promote drug craving and precede relapse episodes in humans, but the underlying neural circuitry by which stressors drive cocaine seeking is not completely understood. Our laboratory has recently focused on the potential involvement of subdomains within the periaqueductal gray, a midbrain region well-established to play a prominent role in the coordination of physiological and behavioral coping responses to stress. In this study, adult male and female Long-Evans rats were allowed to self-administer cocaine (0.5 mg/kg/inf, IV) in 2-h daily sessions for 20 sessions. During sessions 11, 14, 17, and 20, a tactile cue (perforated polycarbonate enclosure) was placed within the operant chamber, and these sessions were immediately followed by one of the following events in separate groups of animals: social defeat stress (SDS, n=16;), intermittent, unpredictable footshock (FS; n=12), or a no-stress empty-cage control condition (NS, n=12). Beginning on day 21, animals underwent extinction training during which lever-presses were not reinforced. Once responding was extinguished, rats were re-exposed to the tactile cue that signaled their assigned stress/no-stress stimulus, and reinstatement of cocaine-seeking was measured for 2 h under extinction conditions. Immediately after the reinstatement test, animals were sacrificed, and brains collected and processed for expression of the immediate early gene c-Fos via immunohistochemistry. Our results revealed a small cluster of Fos-positive neurons in the midline region of the rostroventral periaqueductal gray that was significantly and positively correlated with cocaine-seeking magnitude regardless of the stimulus used to elicit the cocaine-seeking response, as well as with the neural activity of several other brain regions associated with stress responsivity and/or reward seeking. Furthermore, in the SDS group, Fos expression within these neurons was significantly correlated with the display of “active-defensive” behavioral coping responses to social threat. The cluster is located in the vicinity of both the centrally-projecting Edinger-Westphal nucleus (EWcp) and the dorsomedial aspect of the dorsal raphe (DR). Tissue sections were therefore separated on the basis of rostral-caudal extent (differentiating EWcp from DR), and updated correlation analyses revealed that both EWcp and DR are significantly and positively correlated with cocaine seeking magnitude, although the correlation was more robust for the EWcp. Collectively, these data suggest that a cluster of neurons within either or both the EWcp and dorsomedial DR may play a role in cocaine-seeking behavior.
94. Oyku Dinckol Perni
Post-Doctoral Fellow
Advisor: Ronald EllisMunir Gunes Kutlu
Title: Insular acetylcholine release signals competition between conspecifics in mice
Abstract: Acetylcholine (ACh) is a neurotransmitter with multifaceted roles in cognitive processes, including attention, and facilitation of learning. Importantly, ACh signaling is known to be critical for acute physiological and behavioral responses to stress. In this study, we aimed to investigate the role of ACh release in the insula, a brain region critical for complex emotional and social processing, in mediating social competition by using fiber photometry recordings during behavioral tasks. First, we recorded the anterior insular ACh release while animals were competing over a warm spot in a cold arena. Results revealed that the ACh levels increased with distance to the warm spot and the animal’s speed and decreased with the distance to the competing conspecific. Interestingly, when the competitive element (i.e., the warm spot or the competing conspecific) was removed the insular ACh release was not affected by the distance to the previous warm spot corner or the conspecific in the arena. Furthermore, we tested our animals in a tube dominance test where they were competing against a companion blocking the exit route of a tunnel. Consistent with previous results, we found elevated insular ACh release when they go against another mouse and this effect was absent if the competing animal was removed. Thus, these results suggest that the increased insular ACh release plays a critical role in social settings by signaling competition.
95. Noah Wenger
Laboratory technician
Advisor: Munir Gunes Kutlu
Title: Threat-driven acetylcholine release in the anterior insula
Abstract: Previous studies have shown that the insular cortex is involved in a variety of functions such as pain and temperature perception, somatomotor control, auditory processing, and emotions. However, it also serves as an area of convergence for information from multiple cortical and subcortical brain regions. In this study, we investigated acetylcholine (ACh) release in the anterior insula during threat learning. Using fiber photometry combined with a genetically encoded sensor, we measured ACh release in the anterior insula during fear conditioning (i.e., a cue signals footshocks) and fear extinction (i.e., the cue no longer signals a footshock). These experiments revealed that there was a positive ACh response at the time of the predictive cue and the footshock outcome. During fear extinction, the cue ACh response decreased progressively as the animals learned that the cue no longer predicted a footshock. These results suggest that insular ACh signals the negative valence of cues and outcomes. As future aims, we will identify insular single-cell ensembles responsive to negatively valenced stimuli and how insular ACh shapes these ensembles throughout threat learning.
96. Mahdie Kerdari
M.D
Advisor: Christopher Janson
Title: Role of CNS-Border Macrophages in Alzheimer’s Disease
Abstract: Insufficient clearance of Aβ and tau peptides from the brain is a major feature of Alzheimer’s disease (AD) pathophysiology. Understanding clearance pathways and their bottlenecks, therefore, has high translational value. It has been shown that amyloid beta (Aβ) inclusions or fibrillar amyloid are commonly found in aged or AD meninges. 1Furthermore, Aβ species are associated with macrophages in the meninges that envelope the brain and form CNS-border. 2 While the role of brain phagocytes (microglia) in amyloid clearance is well-established, the contribution of meningeal macrophages (MMs) in waste clearance in AD remains poorly understood (Fig. 1). The goal of this work is to investigate the role of MMs in Aβ clearance. To this end, we collected pilot data on MM populations in rat and non-human primate (NPH) meninges and optimized the isolation protocol of MM primary cultures for older animals. Methods: Immunostaining. Rat and non-human primate (NHP) meninges were dissected and processed for immunostaining with respective antibodies, subjected to tissue optical clearing, and 3D imaged with Nikon A1 confocal. Transmission Electron Microscopy (TEM). Aβ-40 peptide with a gold tag (Au) was stereotactically injected into the left ventricle of a young rat. Meninges were collected after infusion and processed for TEM. Meninges were embedded as a whole, regions of interest identified, and ultrathin sections cut and stained. TEM imaging was performed with JEOL electron microscope. MM isolation. Primary macrophages were isolated from freshly dissected rat meninges. Following digestion with the enzymes, cells were incubated with anti-CD206 antibody conjugated with Alexa Fluor® 488. CD206 is a MM surface marker, which allows cells to be sorted by flow cytometry (FACS). After FACS, our isolated population was grown in culture. Conclusion: 1. We showed that MMs are present in rat and NPH meninges at high density. 2. MMs internalize Aβ-Au in vivo infused into the CSF of a rat. 3. Pilot macrophage isolation from older rats showed that meningeal cells, and specifically MMs, are vulnerable to in vitro manipulations and the technique will be further optimized to increase cell viability.
97. Mahdie Kerdrai
M.D
Advisor: Christopher Janson
Title: Mapping Meningeal Vasculature in Non-Human Primates
Abstract: Objective: Provide solutions for the technical barriers in imaging and analysis of opaque, large and thick non-human primate (NPH) dura, to precisely map blood and lymphatic vasculature, matrix, and immune cells. Successful fluorescent-based imaging of whole-mount dura is currently only feasible for rodent dura, which is a small and transparent tissue. Methods: Here we used protocols for tissue clearing with high content of extracellular matrix in conjunction with confocal resonance scanning of large areas with the thickness over 1000µM. Dura was collected from Cynomolgus monkey (Macaca fascicularis) and Rhesus monkey (Macaca mulatta). Conclusion: We developed clearing, mounting and imaging protocols that permitted fluorescence-based microscopy of NPH dura. These new techniques are directly applicable to primate models of neurodegenerative diseases with a focus on the complex interplay between meningeal arteries, veins, and lymphatics.
98. Benjamin Jelen
Post-Doctoral Fellow, PhD in Environmental Microbiology
Advisor: Eli Moore
Title: The Intrinsic Qualities Driving Iron and Nickel Mineral Evolution are Recapitulated in their Coordination Sphere Characteristics Across Protein Space
Abstract: The interactions between different constituent elements determine the physical properties of minerals and are central in the function of protein active sites. Minerals show an expanding range of mineral electronegativity associations as the Earth’s surface became progressively more oxidized over the course of its history. That is, the differences in electronegativity between constituent elements within minerals has increased along with the time of mineral formation on Earth, largely due to an increasingly oxidized setting over Earth’s 4.5 billion year history. To understand if these trends are carried over into biology, we turn to proteins containing transition metals with known 3D structures deposited in the Protein Data Bank (PDB). By analyzing the amino acid residues that fall within a threshold distance from each metal cluster, we quantify the hydropathy of metal-binding sites across the PDB, for nickel (Ni), iron (Fe) and their cluster types. The data show that Fe, found in a wide range of protein types, is inherently more flexible than Ni in how hydrophobic its protein fold space can be. Nickel, found in a far smaller number of protein types, requires more hydrophilic metal binding sites. In both the cases of Ni and Fe, the coordination sphere is more hydrophilic when binding only the transition metal ion, and requires higher hydrophobicity if the transition metal is part of a cluster. With similar trends seen in biological and mineral evolution data, we intend to further characterize the metal coordination spheres of Ni and Fe in cases across the PDB to more clearly understand what drives them. This work adds to our understanding of how the evolution of life on Earth has been enabled by intrinsic qualities of elements and minerals and how different sets of elemental and mineral constituents would enable and affect life’s evolution elsewhere in the universe.
99. Jose de Jesus Argueta Donohue
Advisor: Eli Moore
Post-Doctoral Fellow
Title: Distinctive interactions between glucocorticoid receptor isoforms and caveolae protein influence their sub-cellular trafficking in asthmatic cells
Abstract: Asthma, a respiratory disease characterized by abnormal airway contraction, can lead to lethal in a subset of patients despite treatment with glucocorticoid (GC). The lack of an appropriate or no response to treatment in these patients is a complex, multifactorial process. One model exploring this complexity involves respiratory tract smooth muscle cells (SMC), particularly in asthma subjects, to unravel the underlying mechanisms. A critical factor in this context is the behavior of glucocorticoid receptors (GR), encompassing its various isoforms (𝛼, 𝛽), its ligand affinity, its gradient concentration, its cellular distribution, its protein interactions, and its related cell signaling pathways. Within the cellular membrane, these receptors may interact with lipid raft proteins, including caveolae (Cav1), potentially influencing their sub-cellular trafficking, including translocation from the cytosol to the membrane or the nucleus. Therefore, we hypothesized that SMC from asthma subjects may exhibit distinctive GR-Cav1 interactions and cellular translocation patterns. Specifically, we posit an increased redistribution of GR isoforms in the membrane, cytosol, and nucleus in response to ligands due to differential interactions with caveolae in asthma subjects versus healthy subjects. The objectives were to analyze GR presence in the membrane, cytosol, and nucleus in asthma and non-asthma SMC and to examine the interaction between Cav1 and GR (𝛼 and 𝛽) in these cell types. Flow cytometry experiments revealed a more pronounced cellular redistribution response of GR in asthma subjects after a 15-minute ligand stimulus. Confocal microscopy experiments indicated a higher spatial proximity of GR𝛽 to Cav1 in asthma subjects. These disparities in the spatial distribution of GR isoforms may indicate reduced interaction with membrane proteins (Cav1) in asthma subjects, potentially affecting GR function and glucocorticoid cellular responsiveness.
100. Pavan Goud Juluri
MS in Pharmaceutical science
Collaborators: Jacob Matthew Mara
Advisor: Omar Tilba
Title: Caveolin-1 Interaction with Membrane Glucocorticoid Receptor: Bridging Genomic and Non-genomic Pathways in Airway Cells
Abstract: Glucocorticoids (GCs) are a class of steroid hormones, with cortisol being the primary GC in humans. These hormones play pivotal roles in diverse physiological processes, including the regulation of immune responses, metabolism, and anti-inflammatory actions. Acting through both genomic and rapid non-genomic pathways, it has been elucidated that the latter is facilitated by a distinct GC receptor (GR), the membrane GR (mGR). As implied by its nomenclature, mGR is associated with the plasma membrane; however, its expression, precise localization, and function in airway cells remain yet to be determined. To this end, we treated primary airway smooth muscle (ASM) cells with diverse GCs. Due to its ability to permeate the cell membrane, cortisol engages with both the cytosolic and membrane GRs (cytosolic GR (cGR) and mGR). In contrast, cortisol BSA, incapable of crossing the cell membrane, selectively interacts with mGR alone. ASM cells were also treated with different pharmacological inhibitors such as Cycloheximide (protein synthesis inhibitor), Methyl(B)Cyclodextrin & Nystatin (cholesterol-depleting agents on the membrane disrupting the lipid raft), and Actinomycin D (transcription inhibitor). Whole cell lysates were then prepared and analyzed by western blot to assess mGR's expression and function/involvement using antibodies against p-Ser211, total GR, Beta-Actin, and Caveolin-1 (Cav1). Our findings indicate that the interaction between Cav1 and mGR mediates, at least partially, both genomic and non-genomic effects of GCs. Further investigation, however, is still needed to validate these observations, involving a comprehensive assessment of mGR/Cav1 complex in mediating various actions of the GCs, including anti-inflammatory or anti-proliferative effects.