Genetics Commons^™

Understanding P53 Regulation On Transposable Elements In Cancer, Xuan Qu

Arts & Sciences Graduate Student Theses and Dissertations

Transposable elements (TEs), traditionally known as “jumping genes”, are known to have the ability to move in the genome and alter the activation of transcriptions from nearby genes. Taking up nearly half of the human genome, TEs have evolved, and some have been selected to play important roles in biological processes. We found that in human diseases such as cancer, global hypomethylation resurrects many ordinarily silenced TEs. These TEs can often serve as alternative promoters for oncogenes and play functionally meaningful roles in driving disease processes. One of the top genetic mutation status that correlates with differential numbers of TE …

A Randomized Study Of Digital Versus Genetic Counselor Return Of Actionable Genetic Research Results To Biobank Participants (Respect3 Study), Anuja Rajendra Godbole, Elisabeth Wood, Brian Egleston, Lily Hoffman-Andrews, Sarah Brown, Sarah Howe, Sanjana Shastri, Rajia Mim, Justin Feng, Anjali Owens, Susan Domchek, Reed Pyeritz, Bryson Katona, Staci Kallish, Giorgio Sirugo, Joellen Weaver, Linda Fleisher, Kuang-Yi Wen, Elena Elkin, Katherine Nathanson, Daniel Rader, Angela Bradbury

Department of Medical Oncology Faculty Papers

BACKGROUND: There is consensus that research participants should be informed about plans for return of genetic research results. However, best practices for return of results in large biobank and cohort studies do not exist currently, and how best to communicate actionable genetic research results remains unclear. While having genetic counselors disclose these results may be ideal to ensure understanding, minimize distress, and optimize medical follow-up, genetic counselor (GC) workforce shortages and costs are barriers. The RESPECT3 study evaluates whether digital delivery alternatives for pre-disclosure education and return of actionable genetic research results is non-inferior to remote telehealth disclosure by a …

Multiplex Functional Assessment Of Variant Effect In The Retinal Transcription Factor Crx, James Lewis Shepherdson

Arts & Sciences Graduate Student Theses and Dissertations

The transcription factor Cone-Rod Homeobox (CRX) is a master regulator of photoreceptor cell fate. Sequence variants in CRX can cause Retinitis Pigmentosa, Cone-Rod Dystrophy, and Leber Congenital Amaurosis, all inherited causes of vision loss and blindness. CRX is the only gene implicated in the pathogenesis of all three of these diseases, which present with both rod- and cone-centric phenotypes of varying age of onset and severity. Several CRX variants have been reported to cause severe dominant disease through antimorphic genetic interactions with wild-type CRX, and yet these mutations are adjacent to variants which are benign or only cause mild, recessive …

The Role Of The Virb Ligand Ctp In The Molecular Mechanism Of Transcriptional Anti-Silencing In Shigella Flexneri, Taylor M. Gerson, Monika M A Karney, Helen Wing

Life Sciences Faculty Research

In bacteria, nucleoid-structuring proteins bind and constrain DNA, often leading to transcriptional silencing. In Shigella spp., the histone-like nucleoid-structuring protein H-NS silences many genes on the large virulence plasmid. Upon a shift to human body temperature, VirB, a DNA-binding protein and key transcriptional regulator of the Shigella virulence cascade, is produced. VirB counteracts H-NS-mediated transcriptional silencing and belongs to a fast-evolving clade of the ParB superfamily. Like other ParB proteins, VirB binds the ligand CTP. While CTP is essential for the anti-silencing activity of VirB, the role of CTP in the mechanism of VirB-dependent anti-silencing has yet to be …

How To Measure, Analyze, And Interpret Age-Related Changes In Caenorhabditis Elegans: Lessons For Mechanistic And Evolutionary Theories Of Aging, Zuzana Kocsisova, Brian M. Egan, Andrea Scharf, Xavier Anderson, Franziska Pohl, Aaron Anderson, Kerry Kornfeld

Biological Sciences Faculty Research & Creative Works

Aging is characterized by progressive degenerative changes in tissue organization and function, some of which increase the probability of mortality. Major goals of aging research are to elucidate the series of events that cause degenerative changes, and to identify environmental, pharmacological, and genetic factors that influence these changes; this information might lead to new strategies to extend health span and lifespan. Mechanistic studies of aging depend on accurate and precise descriptions of age-related changes, since these descriptions define the aging phenotype. Here, we review studies that describe age-related changes in C. elegans, including measurements of integrated functions such as behavior …

Reverse Micelles Produce Hydroxyapatite Nanoparticles As More Efficient Gene Delivery Carriers Than Regular Micelles, Vuk Uskoković

Administration and Staff Articles and Research

Hydroxyapatite (HAp) is an effective inorganic gene delivery carrier due to its ability to transport genetic cargo across cell membranes, protect it from proteolysis, and enable escape from late endosomes via pH-controlled dissolution. However, its transfection efficiency remains lower than that of viral agents, prompting studies of hybrids with cationic molecules or phases to enhance the gene delivery performance. This study reports on the synthesis of HAp in regular and reverse micellar regions of a ternary microemulsion system composed of cetyltrimethylammonium bromide (CTAB), 1-hexanol and water. Spectroscopic characterization revealed that CTAB headgroups adopted more ordered supramolecular conformations in reverse micelles …

Comparative Evolution Of Caenorhabditis Hermaphrodites, James Francis Kennedy

Theses and Dissertations

The Caenorhabditis genus produced three independently-evolved hermaphroditic species, C. elegans, C. briggsae, and C. tropicalis. This convergence happened by the independent co-option of male programs for use in a female body. This required two distinct steps: (1) mutations in the sex-determination pathway that activated spermatogenesis in XX animals, and (2) mutations that expressed one of the redundant sperm activation signals in XX animals. My project focused on characterizing how sex-determination genes work in C. briggsae and C. tropicalis. Loss-of-function alleles were used to compare the core sex-determination pathway to that of C. elegans. I found that the somatic sex-determination pathway …

Oer Textbook Review For Human Inheritance - Chromosomes, Genes, And Traits - An Introduction To Genetics, Maria Lazebnik

Open Educational Resources Publications

This review evaluates the adoption and classroom integration of the open educational resource Chromosomes, Genes, and Traits: An Introduction to Genetics for NAS322: Human Inheritance. The instructor found the OER to be comprehensive, accurate, and well aligned with core human genetics concepts, though some content areas—particularly mutations and certain visual diagrams—required supplementation or revision. The flexibility of the OER allowed for significant reorganization, modular use, and removal of non-human examples to better suit course objectives. Integration into Brightspace improved accessibility, reduced student confusion around textbook requirements, and enhanced engagement through direct linking and built-in quizzes. Compared to the previously used …

The Yeast Checkpoint Kinase Mec1p Functions In Transcription Termination By Facilitating Recruitment Of Pcf11p And Regulating The Torpedo Exonuclease Rat1p, Riddhi Patel

Theses and Dissertations

My dissertation includes two projects, centered on transcription regulation by checkpoint kinases of the DNA damage response (DDR). The first project focused on the role of checkpoint kinase Mec1p in transcription termination and regulation of the torpedo exonuclease Rat1p. Termination, closely linked with pre-mRNA 3’ processing, dissociates RNA polymerase II (RNAPII) from DNA and releases the nascent RNA transcript. Efficient termination is required for maintaining a pool of RNAPII that is available for re-entry into new transcription cycle. Previous results showed that inactivation of Mec1p in the absence of exogenous genotoxic stress downregulates the efficiency of transcription termination. This study …

Generating A Gfp Reporter Via Crispr To Visualize Ssa4 Export, Aara Khairollahi, Rebecca Adams

SPARK Symposium Presentations

In eukaryotic cells, the transport of mRNA from the nucleus to the cytoplasm is a very regulated process controlled by nuclear pore complexes (NPCs). During stress conditions, such as heat shock, most mRNA export is inhibited in Saccharomyces cerevisiae, yet the transcript for SSA4, a gene responsible for refolding denatured essential proteins, is exported. The mechanism behind this selective export remains unknown. To investigate this, we used CRISPR-Cas9 to generate a reporter strain in which the SSA4 open reading frame was replaced or inserted with green fluorescent protein (GFP). This reporter is designed to produce GFP only under conditions that …

Physiologic Markers Of Mortality In Acute Valve Syndrome: An Ischemic Physiology Score Stratifies Patient Risk, Omar Saleh, Nicholas J. Valle, Israa Saleh, Raymond Benza, Deepak R. Talreja, Matthew R. Summers

Department of Medicine Faculty Publications

Background: Acute valve syndrome (AVS) represents a high-risk phenotype of advanced valvular disease with largely uncharacterized risk heterogeneity. We aimed to validate an expanded AVS definition and develop a physiology-dependent risk stratification tool using available clinical markers.

Methods: This retrospective study analyzed 2380 patients undergoing aortic valve replacement for severe aortic stenosis and classified them as AVS (n = 1556) or progressive valvular disease (n = 824). The primary outcome was 1-year all-cause mortality. An L2-regularized logistic regression model was developed to predict 1-year mortality using admission laboratory markers and comorbidity burden. Model performance was assessed using nested cross-validation with …

Integrating Genetic Modifier Genotype With Serum Proteomics In Duchenne Muscular Dystrophy Clinical Trials Links Ltbp4 Genetic Modifier To Il-23/Cd93 Pathways In Muscle, Utkarsh J. Dang, Yuan Fang, Daniele Sabbatini, Elena Pegoraro, Luca Bello, Paula R. Clemens, Michela Guglieri, John Van Den Anker, Jesse Damsker, Laura Hagerty, Yetrib Hathout, Michael Ziemba, Lauren Morgenroth, Surajit Bhattacharya, Kanneboyina Nagaraju, Jyoti K. Jaiswal, Eric P. Hoffman

Mathematics & Statistics Faculty Publications

Genetic modifiers of Duchenne muscular dystrophy (DMD) that alter disease severity or response to therapy have been reported using natural history or registry data sets of older corticosteroid-treated patients. We tested associations of genetic modifiers on motor function outcomes in young (4 to <  7 years) steroid naïve clinical trial participants. Participants in clinical trials (VBP15-002/003 [n = 48]; VBP15-004 [n = 121]; DNA available for n = 110) were genotyped for eight published genetic modifier loci, and associations of genotypes with baseline motor function defined via an age-adjusted linear model. Corticosteroid drug response was modeled by genotype-stratified placebo vs. steroid treatment at 12- and 24-weeks posttreatment (mixed model for repeated measures). …

Metabolic Reprogramming Following Mitochondrial Transfer Between Idh2-Mutant Chondrosarcoma Cells And A Normal B-Cell Line, Caleb Wyckoff, Christopher Osgood, Ellen Jing, Michael Stacey

Bioelectrics Publications

Background/Objectives: Chondrosarcoma, glioblastoma, acute myeloid leukemia, chronic lymphocytic leukemia, and cholangiocarcinoma cancers all contain mutations in the gene isocitrate dehydrogenase 2 (IDH2). The mutant IDH2 enzyme metabolizes alpha-ketoglutarate (αKG) into the potent oncometabolite D-2-hydroxyglutarate (D2HG) in the mitochondria of these cancers, leading to altered cellular metabolism. Emerging evidence suggests that mitochondrial transfer between cancer and recipient cells represents an important form of intercellular communication that may influence cellular metabolism. The presence of intercellular TNTs between IDH2-mutant chondrosarcoma cells motivated an investigation into mitochondria-associated physiological changes occurring during an intercellular exchange with immune cells. A mitochondrial transfer is a two-way …

Toward Interpretable Multi-Omics Multimodal Biomedical Artificial Intelligence, Yanjun Lyu

Computer Science and Engineering Dissertations

The complexity of human disease arises from biological processes that unfold across multiple scales, from molecular variation through cellular function, tissue organisation, brain phenotypes, each of which is associated with distinct measurement modalities, regularities, and characteristic. Contemporary biomedical artificial intelligence has brought the opportunity to reveal the complexity with in; however, its methodological default, in which models are trained on most readily available modality, does not adequately engage with the multi-scale connected structure by which biological meaning is constituted. The research area of multi-omics and multi-modal AI for biomedicine remains at an early exploratory stage, and the work presented in …

A Framework For Characterizing The Peripheral Immune Isonome Using Long-Read Single-Cell Rna Sequencing And Its Relevance To Neurological Disease, Patricia Hayes Doyle

Theses and Dissertations--Neuroscience

Long-read single-cell RNA sequencing provides an opportunity to understand human health and disease at isoform resolution, revealing cellular diversity and disease mechanisms difficult to resolve with bulk or short-read methodologies.

Using a modified PIPseq workflow and computational pipeline adapted for Oxford Nanopore (ONT) sequencing, we profiled isoform usage across immune cells, integrating marker expression and isoform discovery, generating the largest long-read single-cell dataset of human immune cells from a single individual to date. We identified non-canonical protein-coding variants of GZMB and CD3G enriched in unexpected cell types. We also discovered novel transcripts from CMC1 and LYAR with cell-type-specific signatures that …

Tmem116 Crispr-Mediated Knockout Prevents Proper Lens Regeneration In Iberian-Ribbed Newts, Damien T. Mann

Honors Theses and Capstones

Eye diseases like cataracts, age-related macular degeneration (AMD), and glaucoma are widespread and detrimental conditions affecting many people across the globe. While there are reliable and successful treatments for those with cataracts that can reverse vision impediments, others like glaucoma and AMD have limited treatment options. Additionally, eye damage resulting from these conditions is commonly irreversible, establishing a need for new treatment options. The Iberian-ribbed newt, Pleurodeles waltl, is a salamander species primarily studied for their amazing regenerative capabilities. Particularly, these newts are capable of de novo lens regeneration after a complete resection, providing a unique opportunity to study regeneration …

Perfluorooctane Sulfonate (Pfos)-Induced Disruption Of Mitochondrial Activity And Cell Adhesion In Liver Cells, Phuong Dam Nam Tran

Graduate Theses/Dissertations

Perfluorooctane sulfonate (PFOS) is a persistent environmental pollutant associated with potential hepatoxic effects and other health risks. Despite its widespread distribution, the mechanisms underlying its toxicities remain to be fully understood. To investigate PFOS toxicology, my study utilized HepG2 and THLE-2 human hepatic cell models to replicate conditions reflecting PFOS accumulation in the liver. Cell viability, cell stress, and cell death assays were conducted to assess the toxicological influence of the chemical on both cell lines. Total RNA extraction was performed, followed by cDNA sequencing, and RT-qPCR. The XTT viability assay revealed a dose-dependent decrease in number of viable cells …

Computational And Ai Frameworks For Identifying Key Regulatory Genes And Their Target Genes In Plants And Humans, Md Khairul Islam

Dissertations, Master's Theses and Master's Reports

This dissertation presents computational and AI-driven frameworks for identifying key regulatory genes and their downstream targets across plant and human biological systems. Three studies address distinct challenges in genomic regulation using advanced machine learning and bioinformatics approaches.

The first study introduces DyGAF (Dynamic Gene Attention Focus), a dual-attention transformer framework that identifies and ranks disease-relevant biomarker genes by simultaneously modeling independent molecular responses and interdependent regulatory network behavior. Two attention models provide complementary perspectives on gene importance and are fused through a novel combination metric. Applied to COVID-19 nasopharyngeal swab profiles, the attention-weighted representations achieved 94.23% classification accuracy, high sensitivity, …

Larval Genomics As A Viable, Fisheries-Independent Tool For Investigating Population Structure In Tropical Pacific Tunas, Jacob E. Jaskiel, Hannah E. Aichelman, Giulia Anderson, Louw Claassens, James E. Fifer, Christina M. Hernandez, Alexa K. Huzar, Joel K. Llopiz, Jan W. Witting, Sean P. Mullen, Randi D. Rotjan

Biological Sciences Faculty Publications

Understanding how dispersal, life history, and environmental variability shape genetic connectivity in the open ocean remains a central challenge in evolutionary biology. Highly migratory marine predators like tunas have traditionally been considered genetically homogeneous across ocean basins, yet emerging genomic evidence suggests that cryptic population structure can persist even in species with high gene flow and large effective population sizes. We used 2bRAD sequencing of 348 larval and subadult skipjack (Katsuwonus pelamis), yellowfin (Thunnus albacares), and bigeye tuna (T. obesus) collected from the central Pacific across 7 years of sampling to examine species boundaries, …

Overview And Methods Of Molecular Paleontology: A Review, Shelby Touchstone

Williams Honors College, Honors Research Projects

Molecular paleontology—the study of ancient biomolecules preserved in fossils and sediments, including ancient DNA, lipids, and proteins—has motivated researchers since the 1950s, inspiring both scientific inquiry and broader cultural imagination. Think Jurassic Park. This honors thesis presents a comprehensive review of the history, current state, and methods of the field of molecular paleontology. Drawing on peer-reviewed literature and scholarly resources accessed through databases such as EBSCO and Bierce library, this review examines key techniques such as Next Generation Sequencing and amino acid racemization and will go over limitations and controversies in the field. It will also explore potential new …