Fahima Afroja, Ali Moghaddam, Atchimnaidu siriki

Mitogen activated protein kinase (MAPK) cascades function as pivotal signal transduction modules that integrate diverse extracellular stimuli to regulate cell proliferation, differentiation, survival, and stress responses, and their dysregulation constitutes a major oncogenic driving force across multiple human malignancies. Among these, the serine/threonine kinases are significant in the progression of non-small cell lung cancer (NSCLC), where they aberrantly activate the ERK and JNK signaling pathways to drive tumor proliferation and survival. This study aims to design and develop novel small-molecule inhibitors intended to selectively inhibit MAP3K19 protein expression to suppress NSCLC progression. A focused library of pyrazolone-based compounds was designed and prioritized through molecular docking. Subsequently, the lead compounds were synthesized and evaluated for antiproliferative activity against A549 cell lines. Biochemical and cellular assays identified potent candidates that significantly inhibited cell proliferation, colony formation, and migration. Among the synthesized analogs, compound P-167 emerged as the most promising lead, with mechanistic specificity for the inhibition MAP3K19 protein expression and making it a good candidate for the signaling pathway involving downstream members such as MEK, ERK, and JNK. All these results underscore its potential as a scaffold for developing MAP3K19 inhibitor addressing the absence of no FDA approved inhibitor yet. 

Hope Hutson, Guoting Qin, Chengzhi Cai, Gergana Nestorova

Intercellular communication in the brain is a key component of both healthy function and disease onset. Extracellular vesicles (EVs) are released by donor cells and encapsulate RNA, DNA, and proteins that influence gene and protein expression upon uptake by recipient cells. Transcriptomic and proteomic cell alterations have been associated with the development and progression of neurodegenerative diseases including glioblastoma. Glioblastoma carries a poor prognosis, making it crucial to develop studies on the molecular pathways involved in the progression of the disease. Comparative mass spectrometry proteomic analysis was performed using EVs from healthy human brain cells and an LN-229 glioblastoma cell line. Data analysis was performed using Spectronaut software (version 18.3, Biognosys). Our results indicate that astrocytes had the highest abundance of enriched EV proteins compared to Human Endothelial Brain Cells (HEBC) and neurons. An upregulated Mitogen-Activated Protein Kinase-Activated Protein Kinase 2 (MK2) pathway was identified in glioblastoma compared to healthy cells. Establishing these EV proteomic profiles will help provide a baseline for detecting disease-related changes that will contribute to early diagnosis of neurodegeneration. Future studies will focus on characterizing a consistently upregulated glioblastoma-derived EV protein, Thrombospondin-2 (THBS2), and assessing the efficiency of plant-derived EVs as nanocarriers for small drug delivery. 

Aliyah Soileau

In eukaryotes, cell type-specific genes enable the cell to perform its specialized functions within an organism. Because of this, these genes are highly regulated. Our work focuses on the SRB8 gene of Saccharomyces cerevisiae, encoding one of the subunits of the CDK8 kinase module within the Mediator complex, an important transcription regulator. SRB8, whose human paralog is MED12, works to interpret internal and external signals that interact with nuclear transcriptional machinery, including transcription factors, RNA polymerase II, and the Mediator complex, to regulate gene expression and determine cellular fate. Our research establishes baseline conditions for detecting transcription factors in S. cerevisiae. Because accurate detection of SRB8 expression depends on high-quality RNA, we obtained high-quality RNA samples quantified using Nano-drop spectrophotometry followed by RT-PCR, endpoint PCR, gel electrophoresis, and visualization to validate our RNA extraction protocol, providing a reliable framework and reproducibility for transcript-level molecular genomics analysis. This is foundational work for our future research using S. cerevisiae SRB8 as a model of the human MED12’s functions in gene expression regulation.

Favour Aina, Prakash Meppaloor Gopalakrishnan Nair

Acinetobacter baumannii is a major opportunistic human pathogen capable of forming biofilms on biotic and abiotic surfaces, contributing to persistent infections and reduced antibiotic efficacy. Therefore, the development of alternative or adjunct therapeutic strategies represents a promising approach for treating biofilm-associated infections. Myrtenol, a bicyclic monoterpene commonly found in essential oils, exhibits a wide range of biological activities, including antimicrobial, antibiofilm, antioxidant, and anti-inflammatory effects. In this study, myrtenol demonstrated significant antimicrobial and antibiofilm activity against A. baumannii without affecting bacterial cell viability, as confirmed by the Alamar Blue assay. Sub-inhibitory concentrations of myrtenol reduced ring biofilm formation, biofilm biomass, surface coverage, and biofilm development on multiple surfaces. Additionally, exposure to myrtenol decreased surface motility and increased susceptibility to oxidative stress. Synergistic testing with Ciprofloxacin indicated enhanced bacterial sensitivity to the antibiotic. The ethidium bromide cartwheel assay demonstrated inhibition of efflux pump activity following myrtenol treatment. Overall, this study highlights the effectiveness of the phytochemical myrtenol in inhibiting A. baumannii biofilm formation and enhancing antibiotic susceptibility, underscoring its potential as a therapeutic agent for managing A. baumannii infections.

Raleigh Billiot, Trista Bonvillain, Bliss Broussard

Vibrio vulnificus is a Gram-negative bacillus and opportunistic pathogen native to the Gulf Coast. This bacterium has been observed to accumulate in weathered tar balls, with cell concentrations exceeding the surrounding seawater by a factor of 100. This affinity towards hydrocarbons was also investigated and determined to occur in vitro in the laboratory using the model oil compound, n-hexadecane. Biofilm assays demonstrated that Vibrio preferentially associates with oil over plastic under static incubation conditions in artificial seawater (ASW). To further investigate the nature of this interaction, assays were performed to assess the binding capability of Vibrio cells to glass beads, uncoated or coated with oil. Results indicated a high level of binding to both coated and uncoated beads in ASW media, which was not similarly observed in LB2 media, suggesting that the ionic strength of the media may strongly influence this interaction with oil. Bacterial adhesion to hydrocarbons (BATH) assays using isogenic colonial phase variants of V. vulnificus expressing different cell surface chemistries all showed similar affinities toward oil in PBS (isoionic), while repeated BATH assays in ASW media (hyperionic) yielded inconclusive results. Future work continues to focus on hydrocarbon adhesion at the air-surface interface using pellicle assays. Defining the ecological patterns of Vibrio spp. in contaminated waters critical to inform seafood safety and public health policies.

Sarina Khadka, Doreen Aidoo, Pradip Panta

The DedA protein family comprises highly conserved inner membrane proteins with poorly defined physiological roles. Recent evidence suggests that some DedA proteins function as undecaprenyl phosphate (Und-P) flippases. Und-P is an essential lipid carrier required for cell wall biosynthesis, lipid A aminoarabinose modification, and capsule production, key determinants of bacterial virulence, making it an attractive therapeutic target. Here, we show that deletion of two redundant DedA homologs, YqjA and YghB, markedly sensitizes Klebsiella pneumoniae to bacitracin, an inhibitor of Und-P recycling, indicating that these proteins are required for efficient Und-P turnover. Loss of DedA proteins leads to constitutive activation of the PhoPQ two-component system, a major virulence regulator, and increases sensitivity to substrates that elevate electron load, such as the long-chain fatty acid oleate. In the absence of DedA proteins, PhoPQ-dependent upregulation of ispU, encoding the enzyme responsible for de novo synthesis of Und-PP, was observed. Consistently, phoP and phoQ transposon mutants exhibit increased bacitracin sensitivity. Together, these findings demonstrate that impaired Und-P recycling drives sustained PhoPQ activation. While this response may enhance virulence, it imposes a fitness cost under conditions of high electron load and elevated ATP demand. We propose that combining Und-P recycling inhibitors with long-chain fatty acids may enhance therapeutic efficacy.

Abeeb Oyesiji, Shila Kandel, Abubakar Abdulkadir, Eduardo Martinez-Ceballos, Xiaoping Yi, Raphyel Rosby, Md Ekhtear Hossain

Prostate cancer is one of the most commonly diagnosed malignancies among men in the US and a leading cause of cancer-related mortality. Beyond genetic and lifestyle risk factors, environmental pollutants are increasingly recognized as potential drivers of disease progression. Tire wear compounds (TWCs), generated through tire–road abrasion, represent a pervasive yet understudied class of environmental contaminants. Among these, 4-aminodiphenylamine (4-ADPA) is widely used as an antioxidant in tire manufacturing; however, its biological effects on cancer remain unknown. This study examined whether 4-ADPA promotes prostate cancer cell proliferation by modulating the PI3K/AKT/mTOR signaling pathway, a central regulator of tumor growth and therapy resistance. DU-145 prostate cancer cells were exposed to increasing concentrations of 4-ADPA. Cell proliferation was measured using the CCK-8 assay, and transcriptional changes in PI3K, AKT, and mTOR were assessed. Exposure to 4-ADPA significantly enhanced DU-145 cell proliferation and induced marked upregulation of AKT and mTOR, while PI3K expression remained unchanged. These findings indicate activation of PI3K-independent AKT/mTOR signaling, suggesting a bypass mechanism that accelerates tumor cell growth. Collectively, this study provides the first mechanistic evidence that a tire wear–derived pollutant promotes prostate cancer progression via oncogenic signaling.

Cheryl Bardales, Karen Slatten

Alzheimer’s disease (AD) pathology develops years before the onset of clinical symptoms, highlighting the need for sensitive biomarkers and cognitive measures capable of detecting impairment during the preclinical stage. Plasma phosphorylated tau 217 (p-tau217) has emerged as a promising blood-based biomarker associated with amyloid and tau pathology, yet its relationship to baseline cognitive performance in cognitively normal individuals remains under investigation. This study examines the association between baseline plasma p-tau217 concentrations and cognitive performance using archival data from the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) Study. Secondary cross-sectional analyses focus on cognitively normal, amyloid-positive older adults and compare the strength of association between p-tau217 and the Preclinical Alzheimer Cognitive Composite (PACC), emphasizing composite variants excluding the Mini-Mental State Examination. Planned analyses employ multiple linear regression models adjusted for age, sex, education, and APOE ε4 carrier status, with exploratory comparisons across domains. This work aims to evaluate whether alternative cognitive composites demonstrate improved sensitivity to early AD-related cognitive changes and stronger associations with baseline plasma p-tau217. Findings from this ongoing analysis may inform optimization of screening tools and blood-based biomarkers for early identification of individuals at risk for Alzheimer’s disease.

Ernest Owusu Boadi, Siva Murru

Colorectal cancer (CRC) remains a significant global health challenge, particularly in advanced stages where therapeutic resistance is common and five-year survival rates remain low (~12%). This underscores the urgent need for new small-molecule anticancer agents with improved selectivity, reduced toxicity, and enhanced therapeutic efficacy. Small molecules offer advantages such as oral bioavailability, cost-effectiveness, and the ability to modulate intracellular targets involved in tumor progression. Among these, pyrazole-based compounds have demonstrated diverse biological activities, including notable anticancer potential.

Building on our previous work with pyrazole- and pyrazolone-based anticancer scaffolds, we synthesized a new library of fused pyrazole-pyranone hybrids using optimized SNAr substitution and intramolecular cyclization strategies. Reaction optimization, purification, and structural characterization will be presented. Antiproliferative activity was evaluated against colorectal cancer cell lines and a non-cancerous control cell line, alongside functional and migratory assays, including colony formation. Computational target prediction and molecular docking studies further support the potential of this chemotype as a promising platform for CRC drug development.