Oral Presentation Titles, Authors and Abstracts

2026 Oral Presentations

Pathogenicity of L199T Mutation in Apolipoprotein E

Yvonne Anderson

Mentor: Brandon Gines, PhD

Tuskegee University

Vascular dementia is a neurological disease that causes a decline in thinking skills by blocking or reducing blood flow to multiple regions of the brain, which deprives them of oxygen and nutrients. One protein that is associated with vascular dementia is Apolipoprotein E (APOE). APOE is a cholesterol carrier that is produced in the brain and other kinds of tissues. The normal function of APOE within the central nervous system (CNS) and the brain consists of clearing debris for homeostasis, inhibiting inflammation, and promoting neuronal network resilience. Defects within the APOE protein can cause abnormal functions, such as the clearance of Aβ oligomers, the activation of glial cells in response to protein aggregation, and neuronal dysfunction and death. One missense mutation of unknown pathogenicity within APOE is L199T. At the residue position 199, the change from the normal non-polar amino acid leucine to the variant polar uncharged amino acid threonine may or may not impact the proper function of APOE. Several webtools were utilized to predict whether the L199T mutation has a benign or pathogenic impact on APOE’s function. The Poly-Phen2 and SIFT pathogenic prediction tools estimated that the change from leucine to threonine at the 199 amino acid position will have a harmful impact on the protein’s function. In addition, the Aminode conservation analytical tool illustrates the moderate conservation of leucine between various organisms, which indicates the importance that the amino acid leucine has on the APOE protein’s correct function. These webtool predictions indicate that the L199T mutation has a harmful impact on the APOE protein’s appropriate function, even though the YASARA software predicts that there is minimal structural change caused by the missense mutation. The pathogenic impact of this missense mutation can be further researched to find potential treatments for vascular dementia.

Pathogenic Potential of the VPS13C Variant Associated with Early-Onset Parkinson’s Disease 

Kiar-Ra Cameron

Mentor: Marie-Claire Boutrin, PhD

Oakwood University

Parkinson’s disease (PD) is classified by symptoms including tremors, bradykinesia, and difficulty speaking (motor symptoms), and memory loss, mood disorders such as depression, and difficulty reasoning (non-motor symptoms). It affects many individuals worldwide and has now widened from an old-aged to a middle-aged condition. PD is identified as a lipid-induced proteinopathy where changes in lipid composition or metabolism induce protein alteration. The Vacuolar Protein Sorting 13 Homolog-C (VPS13C) gene encodes for lipid transport proteins that regulate lysosomal function within the cell and VPS13C mutants were linked to PD. This study aims to identify a VPS13C variant linked to PD and the possible implications of the mutation on the mutant protein structure and functions. We hypothesize that the mutation will be associated with structural and functional changes in the mutant VPS13C protein. Bioinformatics tools were used for analysis. Simple ClinVar analysis revealed a missense mutation G1389R VPS13C variant with a CADD score of 34 previously associated with PD. UniProt analysis showed VPS13C isoforms with similar sequences except at sequence positions 152-127 and 3648-3585. PolyPhen2 study predicted the mutation to be probably damaging with a score of 0.986, and a sensitivity score of 0.74. Protein structure analysis suggests modulation in protein structure based on changes from a non-polar amino acid to a positively charged one. STRING studies revealed that VPS13C is involved in a protein network including plasma proteins instrumental in tracking and maintaining homeostasis within the cell such as Synaptojanin-1, F-Box only protein 7, Cation-transporting ATP13A2, and Phospholipase A2. Collectively, our findings suggest an involvement of the G1389R VPS13C variant with PD, with predicted damages to its mutant protein function and possible implications for a protein-protein interactions network. Future studies are warranted to further understand the involvement of the G1389R VPS13C variant in the development of PD.

Potentially Pathogenic Mutant miRNA on its Interactions with Dicer

Jordan Doucet

Mentor: Derrick Watkins, PhD

Athens State University

The function of miRNA is to regulate the production of proteins by silencing a mRNA’s code to inhibit the production of proteins. Dicer is a protein that processes a ~78-nucleotide strand of pre-miRNA cleaving it down to a single stranded mature miRNA that is 22 nucleotides in length. A mutation in a miRNA can lead to disease by contributing to an upregulation of a downregulation of a protein if it forms a silencing complex more often or less efficiently. We hypothesized that a mutation in the miRNA will cause a structural difference in the mutant miRNA that could alter the processing of the pre-miRNA by Dicer. This study investigates the 55G>A mutation of miRNA-142. This mutation occurs in the stem region of miR-142 in close proximity to one of the catalytic sites of the Dicer protein and disrupts the base pairing of the nucleotide in the stem of miR-142. We used molecular dynamic simulation studies to determine the change in the RMSD of the backbone atoms of the pre-miRNA in the Dicer bound and the Dicer unbound miR-142 state of both the wildtype and mutant forms of miR-142. From these studies we observed the energy minimized structure of wild-type miR-142 has a slightly wider backbone than the mutant miR-142, which may indicate the wild-type is trending towards A-form. The mutant miRNA-142 energy minimized structure has a slightly wider minor grove than the “dicing state”, but the minor grove is less wide than the wild-type. The mutant appears to be trending to A-form at a slower rate, which could potentially indicate the mutant is more stable in the “dicing” state. The difference in stability of the mutant compared to the wild-type may result in a difference in processing by Dicer from the mutant compared to wild-type.

In-silico characterization of PSEN1 missense variants associated with acne inversa

Kate Grissom

Mentor: Cynthia Stenger, PhD

University of North Alabama

Acne inversa, or hidradenitis suppurativa, is a chronic inflammatory skin disorder that causes painful and reoccurring abscesses. The PSEN1 gene is responsible for the instructions to the presenilin 1 protein, which is part of the gamma-secretase complex and is responsible for cleaving other proteins to form peptides. Acne inversa occurs for PSEN1 mutations where Notch signaling is disrupted. Analysis of multiple pathogenicity predictors and simulated aqueous environments of the transmembrane protein in its native and mutated state through molecular dynamics simulation predicted deleterious effects from the swap of tyrosine to cysteine at the highly conserved and buried position 189.  

Envelope proteins rare subtypes HIV-1

Kameron Hinton

Mentor: Dana Indihar, PhD

Alabama A&M University

Human immunodeficiency virus type 1 rare subtypes make up less than 1% of total HIV-1 infections globally. Among these, Subtype F1 primarily circulates South Africa, Europe, and

Central Africa. Although subtype F1 is rare, its significance in HIV-1 constantly evolves, making it difficult to prevent worldwide. It is significant to understand the evolution of subtype F1 and how it was able to spread to certain regions of the country to inform medical treatment. However, it is still unknown how the subtype may respond to medical treatment. We predict that subtype F1 Envelope (Env) can influence how HIV-1 may react to medical treatment in a subtype-specific manner. We hypothesize that the structure of the F1 Env differs from the Env of the HXB2 lab reference strain. In this study, we analyzed Env from F1 and HXB2 using YASARA. Structural modeling was used to compare the envelope proteins of subtype F1 and HXB2. The results helped us illustrate structural features and potential differences between subtype F1 Env proteins and the HXB2 reference strain. Overall, this work contributes to a better understanding of subtype-specific complexities of HIV-1 subtype F1 Env.

Characterizing the Pathogenicity of Glycine Swap VUS in STK-11 related to Peutz-Jeghers Syndrome

Heather Weston

Mentor: Cynthia Stenger, PhD

University of North Alabama

Peutz-Jehger’s Syndrome (PJS) is an Autosomal Dominant inherited disorder which results in susceptibility to multiple cancers and possible mucocutaneous pigmentation. PJS originates from deleterious mutations in serine/threonine kinase 11 (STK11), a tumor suppressor gene that prevents unchecked cell growth and reduces toxic reactive oxygen species from accumulating. Research on missense mutations in STK11 is low, with over 90% of the variants being classified as variants of uncertain significance (VUS). Genetic testing is one of the main forms of diagnosing PJS, but a classified variant is required to confirm a test. We chose to examine the pathogenicity of the VUS E223G and D237G due to glycine's deleterious effects on alpha helix structure and the location of these variants on alpha helices. The in silico pathogenicity tools and modeling software Ensembl, ConSurf, YASARA, CADD, and Simple ClinVar were used to analyze the effects of these amino acid swaps on STK11 to characterize them as benign or pathogenic. Based on the simulations, we believe E223G and D237G are deleterious and would result in PJS. Both variants are located within pathogenic hotspots and have higher pathogenicity scores in some tools than known pathogenic variants. Classifications like these are vital due to the lack of information on STK11 VUS and the need for quicker diagnostic testing.

Computational Characterization of the PAH Missense Variant rs62517167 (p.Leu98Ser) and Its Role in Phenylketonuria Pathogenesis

Akaylin Echols

Mentor: Brandon Gines, PhD

Tuskegee University

Phenylketonuria (PKU) is an inherited metabolic disorder caused by mutations in the PAH gene, which encodes phenylalanine-4-hydroxylase, the enzyme responsible for converting phenylalanine to tyrosine. When PAH function is impaired, phenylalanine accumulates in the blood and can lead to neurological complications if untreated. This presentation investigates the missense variant rs62517167 (p.Leu98Ser) and evaluates its potential role in PKU pathogenesis. Using a computational approach, I compared the biochemical properties of the wild-type leucine residue with the substituted serine at position 98. Leucine is a hydrophobic amino acid that stabilizes the protein core, whereas serine is polar and may disrupt local folding. Pathogenicity prediction tools, including PolyPhen-2 and Ensembl VEP, classify this variant as likely damaging. Conservation analysis further indicates that this residue is functionally important. Overall, the findings suggest that the p.Leu98Ser substitution may alter PAH structure and impair enzyme function, supporting its likely pathogenic role in PKU.

Investigating Bacteriophages Pa310 and Y3Z and Their Role in the Lysis of Cutibacterium acnes 

Amya Joy

Mentor: Dana Indihar, PhD

Alabama A&M University

Bacteriophages are viruses that infect bacteria, including C. acnes, which live on human skin. When C. acnes overgrow, it can cause massive inflammation, leading to other skin infections such as cystic, hormonal, and follicle acnes. To reproduce, bacteriophages must break open to the bacterial cell. Special proteins called endolysins help by creating holes in the cell wall, causing the cell to burst and allowing the virus to spread. In this project, we analyzed two phages, Pa310 and Y3Z, which encode endolysins. Both show functions that contribute to the bacterial lysis process. Additionally, strategies used in this study included analyzing and comparing TM-scores, examining the 3D models of each individual protein, and checking percent sequence similarity. These methods helped identify structural and functional characteristics of proteins. Understanding how these phages utilize these proteins can help researchers learn more about how phages infect and kill C. acnes. This knowledge may also help develop strategies to slow the spread of the bacteria, such as strategies to boost endolysin activity or targeting phage attachment to bacteria, which could lead to new treatments for acne and other skin conditions. 

Variant Bioinformatics & Analysis: Do CXCR4 VUSs have increased pathogenicity associated with X4-Tropic HIV-1?

Lauren Karmer

Mentor: Dana Indihar, PhD

Alabama A&M University

Approximately 40.8 million people are living with HIV worldwide. For viral entry to occur, a viral envelope glycoprotein (Env) of human immunodeficiency virus type one (HIV-1)

must bind with the primary receptor CD4, as well as either the CCR5 coreceptor or the CXCR4 coreceptor. Whereas CCR5-tropic viruses preponderate pathogen transmission,

individuals with chronic infections often experience CXCR4-tropic variants correlated with the onset of AIDS. HIV-1’s primary coreceptor CCR5 may contain a 32 base-pair

deletion (CCR5-Δ32) allowing carriers to prevent successful viral attachment by inhibiting binding through the truncation of the CCR5 protein, thus promoting innate

HIV-1 resistance. Nevertheless, research into whether CXCR4 variants that may congenitally influence protein function or pathogenicity, as well as HIV-1 Env binding, is

sparse. Investigating variants of CXCR4 is essential for understanding mechanisms of HIV binding and entry. However, questions remain regarding whether variants of

uncertain significance (VUS) of CXCR4 affect Env binding. We hypothesized that CXCR4 VUS Asp262Glu and Glu268Asp will be pathogenic and affect X4-Tropic HIV-1

Env binding. In this study, we analyzed two CXCR4 VUS using bioinformatic software to determine their pathogenicity and impact on Env binding. Variant effect prediction

programs were used to evaluate beingness, deleteriousness, or protein tolerance. YASARA was used to conduct simulations investigating protein dynamics, folding, and

docking. MEGA12 was used for constructing phylogenetic trees as well as creating multiple sequence alignments. Overall, research into CXCR4 VUS enhances

understanding of CXCR4 pathogenesis, as well as providing a foundation for understanding mechanisms of HIV-1 binding and entry.

Computational Analysis of a TSHR Missense Variant (p. Phe97Ser) Associated with Hyperthyroidism

Kashmere Miller

Mentor: Brandon Gines, PhD

Tuskegee University

Hyperthyroidism is a condition characterized by excessive production of thyroid hormones. One gene associated with thyroid hormone regulation is TSHR, which encodes the thyrotropin receptor. In this study, a missense variant (p.Phe97Ser) in the TSHR gene was analyzed using bioinformatics tools to evaluate its potential impact on protein structure and function. Sequence analysis, multiple sequence alignment, and structural modeling were used to determine whether the mutation occurs at a conserved region of the protein and how the substitution may influence protein stability. Conservation analysis showed that phenylalanine at position 97 is highly conserved across species. Because phenylalanine is hydrophobic and serine is polar, the substitution may disrupt hydrophobic interactions or introduce new hydrogen bonding. These results suggest the variant may influence receptor structure or function and could potentially affect thyroid hormone signaling.

An Analysis of IRF6 Variants Associated with Non-syndromic Cleft Lip and Palate

Gabrielle Murray

Mentor: Marie-Claire Boutrin, PhD

Oakwood University

Non-syndromic cleft lip and palate (NSCLP) is a type of orofacial cleft characterized by openings or separations of the cleft lip and/or palate. It is a complex condition with a genetic predisposition that occurs in 1 in 600-800 babies worldwide. NSCLP is associated with mutations in Interferon Regulatory Factor 6 (IRF6), which is located on the q arm of chromosome 1. IRF6 encodes transcription factors such as IRF6 that are important for embryonic tissue development and is expressed in osteocytes and hypertrophic chondrocytes of craniofacial tissue. Previous studies have reported NSCLP to be associated with Arginine to Glutamine mutation in IRF6 variants at position 9 of a DNA-binding domain, but other mutations such as Arg9Trp have not been studied. It is hypothesized that Arg9Gln and Arg9Trp mutations will compromise the structural configuration of the IRF6 with possible functional implications. This study aims to determine the effects of Arg9Gln and Arg9Trp variants on the pathogenicity, structural configuration and function of IRF6. Simple Clinvar revealed a CADD score of 32 for the Arg9Gln and Arg9Trp variants. PolyPhen-2 predicted the mutations to be probably damaging with a score of 1. YASARA did not show any notable changes in the mutant IRF6 configurations compared to the wild-type. STRING analysis identified the proteins VAX1, MAFB, NECTIN1, and MSX1 to be associated with IRF6 in the development of NSCLP. Since no structural changes were observed in the protein models, the predicted damages to protein function may be solely related to the mutation being located in the IRF6 DNA-binding domain. Collectively, these findings show that the connection between NSCLP and the Arg9Gln and Arg9Trp variants may be due to changes in the DNA binding abilities of the mutant IRF6. Future studies screening for Arg9 mutations in NSCLP patients are warranted.

An analysis of CDC25A variants associated with autosomal dominant polycystic liver disease. 

K'sia Byass

Mentor: Elaine Vanterpool, PhD

Oakwood University

Autosomal dominant polycystic liver disease (ADPLD) is a rare genetic disorder characterized by the formation of multiple cysts in the liver. Many affected individuals remain asymptomatic, and the condition is often discovered incidentally. Although both sexes can develop the disease, ADPLD is more frequently observed in adult women, particularly those with multiple pregnancies or prolonged estrogen exposure. The purpose of this study is to identify and assess the pathogenicity of CDC25A gene variants associated with ADPLD. While several genetic mutations linked to ADPLD have been reported, the role of CDC25A in the disease remains under investigation. We hypothesize that specific genetic variants of CDC25A may be pathogenic and contribute to the ADPLD phenotype.ClinVar was used to identify CDC25A as a gene associated with ADPLD and to select three missense variants for analysis: Ser88Phe, Thr349Ile, and Gln24His. The CDC25A gene encodes the Cell Division Cycle 25A protein, a dual-specificity phosphatase that functions as a key regulator of the eukaryotic cell cycle. Pathogenic alterations in CDC25A can lead to abnormal stabilization or overexpression of the protein, resulting in uncontrolled cell proliferation, genomic instability, and impaired DNA damage checkpoints.CDC25A is primarily localized in the nucleus during the G1 and S phases of the cell cycle and is expressed in various tissues, including the breast, lung, thyroid, and testis. Computational prediction tools PolyPhen-2 and SIFT were used to evaluate the pathogenicity of the selected variants. Both tools predicted the Ser88Phe variant to be damaging, while Thr349Ile and Gln24His were predicted to be tolerated. These findings suggest that the Ser88Phe mutation may disrupt CDC25A function and contribute to abnormal cell cycle regulation, potentially promoting cyst development in ADPLD. Further experimental studies are needed to confirm the functional impact of these variants.

Comparative Study of Missense Variant Ser437Tyr in the MFSD8 Gene Associated with Infantile Neuronal Ceroid Lipofuscinoses

Calvinae Jolly

Mentor: Priscilla Santiago, PhD

Spring Hill College

Infantile Neuronal Ceroid Lipofuscinosis type 7 (CLN7) is a rare inherited neurodegenerative disorder that affects the nervous system. The disease is caused by mutations in the CLN7 gene, located on chromosome 7, which encodes the lysosomal protein MFSD8. CLN7 is a subtype of Batten disease and primarily affects children. Mutations in this gene can result in the production of a defective or nonfunctional protein, impairing normal lysosomal function and ultimately leading to progressive neurodegeneration. According to the ClinVar database, the pathogenicity of approximately 90% of variants in the MFSD8 gene remains uncertain. This study aims to investigate a variant of uncertain significance caused by a missense mutation at amino acid position 437, in which serine is substituted with tyrosine. To evaluate the potential structural impact of this mutation, computational molecular dynamics analysis will be conducted to compare the protein structure before and after the amino acid substitution. Understanding the structural consequences of this mutation may provide insight into its potential pathogenicity and contribute to improved classification of MFSD8 variants associated with CLN7.

Bioinformatic Analysis of the PHF14 Variant, Ala333Thr

Rachael Moriarty

Mentor: Sara Cline, PhD

Athens State University

In 2016, a female child was born at 36 weeks, weighing 5 pounds 13 ounces, with a debilitating white-matter neurodegenerative disorder (Zhou et al., 2022). She presented phenotypes including hypothyroidism and delayed neurological and motor development, resulting in slowed speech and unbalanced walking, with the left leg less functional than the right (Zhou et al., 2022). The plant homeodomain finger protein 14 (PHF14) variant C322G is implicated in the onset of this neurodegenerative disorder (Zhou et al., 2022). The purpose of this study is to investigate the molecular dynamics of two PHF14 variants: the known pathogenic variant C322G and the variant of uncertain significance (VUS) A333T. To determine the pathogenicity of PHF14 VUS A333T, comparisons were made with C322G using database searches, protein alignments, 3D protein models, and molecular dynamics simulations (MDS). This study found that A333T movement displays unique root mean square deviation (RMSD) and root mean square fluctuation (RMSF) levels, suggesting that A333T is potentially deleterious and likely alters PHF14 movement. These changes could render partner effector proteins unable to bind to PHF14, leading to excess cellular proliferation in the brain and analogous harmful phenotypes (Bugiani & Van Der Knaap, 2017; Zhou et al., 2022).

Investigating the implications of missense mutations in the PY-NLS domain of the Fused in Sarcoma protein and their associations with ALS 

Lydia Uptain

Mentor: Cynthia Stenger, PhD

University of North Alabama

Frontotemporal dementia (FTD) is the most common cause of dementia for individuals under the age of 60. It commonly co-occurs with amyotrophic lateral sclerosis (ALS), and when co-occurring, they cause a combined syndrome called ALS-frontotemporal spectrum syndrome (FTD-MND). This syndrome is associated with a buildup of an RNA-binding protein known as the fused in sarcoma (FUS) protein in motor neurons and brain tissue. This buildup is associated with mutations in the protein that cause protein mislocalization and subsequent cytotoxic effects. This study investigates uncharacterized missense mutations in the PY-NLS domain of this protein, with a focus on arginine swaps. The goal of this investigation is to determine if a mutation will lead to a cytotoxic buildup of this protein and cause a pathogenic phenotype. The impact of these mutations was assessed using in silico prediction tools, protein modeling, conservation prediction, and molecular dynamics simulations. A total loss of function in this protein will not display a pathogenic phenotype, but a partial loss of function may have deleterious effects. Results from these various tools and methods determined that a pathogenic phenotype will be observed.

Structural Insights into HIV-1 Env Mutations That Modulate Cell–Cell Transmission

Rondel Hemerding

Mentor: Dana Indihar, PhD

Alabama A&M University

HIV-1 cell–cell transmission (CCT) enhances viral spread and may reduce susceptibility to neutralizing antibodies compared to cell-free infection. Structural determinants within the HIV-1 envelope (Env) glycoprotein that promote this transmission mode remain incompletely defined. In this study, we seek to understand the structural and biophysical consequences of two Env point mutations, R298K and S162K, relative to the wild-type (WT) Env structure 6NIJ. We hypothesized that these mutations alter Env conformational stability, receptor engagement, or structural dynamics. Using structural modeling based on the WT 6NIJ trimer, we examined the local and global effects of the R298K and S162K substitutions. Electrostatic energy analysis showed that solvation and vacuum energies stayed mostly the same across all variants. However, the total electrostatic energy changed slightly, suggesting that R298K slightly stabilizes the protein, while S162K slightly destabilizes it. R298K, located within the gp120 subunit, preserves positive charge but may alter local side-chain interactions and hydrogen bonding networks that influence CD4 binding or trimer stability. In contrast, S162K introduces a positively charged residue at a position commonly associated with glycosylation, potentially disrupting glycan occupancy and modifying Env surface exposure. These structural perturbations may alter energy landscapes and conformational dynamics critical for virological synapse formation. Preliminary analyses suggest that while both mutations are conservative at the sequence level, they may induce measurable shifts in Env flexibility, electrostatics, and receptor binding compared to WT 6NIJ. Together, these findings provide insight into how specific Env mutations

may modulate structural properties to enhance cell–cell transmission and contribute to viral fitness under selective pressure.

Desmolein-2 F833C is Predicted to Disrupt Hydrophobic Interactions of Armadillo Repeat Region 1 of Plakoglobin

Vincent Boutsioukos

Mentor: Eric Johnson, PhD

Alabama College of Osteopathic Medicine

Desmoglein-2 (Dsg2) is a cadherin involved in cell-cell adhesion in cardiac tissue [7]. A Variant of Unknown Significance (VUS), F833C, was identified and analyzed for its potential role in disrupting the interaction between Dsg2 and its intracellular binding partner plakoglobin [14,16]. Molecular dynamic (MD) simulations, pathogenicity predictions, and stability metrics were used to assess its impact. The F833C variant showed significantly decreased binding energy and increased per residue Root Mean Square Fluctuations (RMSF) at the Dsg2 interface. These metrics indicate a potential pathogenic effect due to compromised stability and interactions.