Genetics and Genomics Commons^™

Translation Of The Carcinogenic Dna Breakage-Repair Inhibition Mechanism For Hexavalent Chromium To Its Key Targets: Lung Epithelial Cells, Lung Tissue And Impacts On The Genome., Idoia Meaza Isusi

Electronic Theses and Dissertations

Lung cancer is the leading cause of cancer death worldwide. Hexavalent chromium [Cr(VI)] is a human lung carcinogen with widespread occupational and environmental exposure. Despite the known health risks, how Cr(VI) causes lung cancer remains unclear. This dissertation investigates the mechanisms of Cr(VI)-induced carcinogenesis. Cr(VI) causes DNA damage, specifically DNA double strand breaks, and inhibits homologous recombination repair, a high-fidelity repair pathway. Unrepaired DNA double strand breaks or those repaired through error-prone pathways, progress to chromosomal damage, and chromosome instability. The latter is a common characteristic of Cr(VI)-exposed cells, and a hallmark of lung cancer. Although the mechanism of Cr(VI)-induced …

Gender And Race Stigma Consciousness Denialism And Reactions To Race And Gender Measures, Valerie Partida, Alicia Sylvester, Magel Baker

Celebrating Scholarship and Creativity Day (2018-)

The study examined whether denialism, defined as holding problematic stigma consciousness scores in, predicts emotional reactions to race- and gender-related survey measures. Specifically, we asked whether race stigma consciousness scores correlate with feeling upset when completing race scales, and whether gender stigma consciousness scores correlate with either positive or negative reactions to gender scales. Undergraduate students in introductory psychology courses participated (N = 38; 61 % women/gender minority, 39 % men; 21% POC, 79% White). Measures of students’ awareness of racial and gender discrimination (Pietri et al., 2018) were scored such that high scores meant that students of color (POC), …

Cloning And Heterologous Expression Of Human Nachrs And A Unique Spider Venom Toxin, Christine M. Vega

Theses and Dissertations

Drug development research has long focused on synthesizing novel therapeutics while overlooking isolation from naturally available sources. Recently, the discovery of the therapeutic effects of highly bioavailable animal venom caused the field of venom research to soar in popularity. Animal venom serves as a natural, sophisticated tool optimized over millions of years by evolution with the ability to bind to ion channels such as nAChRs, non-specific ligand-gated ion channels distributed throughout the human nervous system, with high selectivity and specificity. However, purifying individual venom toxins from crude venom is challenging due to its availability. Therefore, synthesizing large quantities of venom …

Therapeutic Applications Of A Novel Humanized Monoclonal Antibody Targeting Chemokine Receptor Ccr9 In Pancreatic Cancer, Hannah G. Mcdonald, Anna M. Reagan, Charles J. Bailey, Mei Gao, Muqiang Gao, Angelica L. Solomon, Michael J. Cavnar, Prakash Pandalai, Mautin Barry-Hundeyin, Megan Harper, Justin A. Rueckert, Ángela Turrero, Araceli Tobio, Anxo Vidal, Daniel Roca-Lema, Elia Álvarez-Coiradas, Pablo Garrido, Laureano Simón, Joseph Kim

Markey Cancer Center Faculty Publications

The relative failure of immune checkpoint inhibitors in pancreatic ductal adenocarcinoma (PDAC) despite having a dense, immunosuppressive tumor microenvironment highlights the need to target alternate/escape pathways. We have previously examined C–C chemokine receptor type 9 (CCR9) as a candidate immune checkpoint and developed a targeted, humanized monoclonal antibody (SRB2). Cytotoxicity of SRB2 was evaluated in vitro and in vivo. CCR9 expression on PDAC cells/tissues, immune components of patient-derived organoids (PDOs), and antibody-dependent cell-mediated cytotoxicity were examined. In PANC-1 and MIA PaCa-2 cell lines, we demonstrated highest CCR9 expression; however, no direct cytotoxic effect was observed with SRB2 treatment. In PANC-1 …

African Sleeping Sickness: From Basic Biology To Future Directions, Riddhi R. Patel

All Theses

African Sleeping Sickness is a Neglected Tropical Disease (NTD) which poses a significant health risk to impoverished populations in 36 Sub-Saharan African countries. It is a devastating disease caused by the protozoan parasite Trypanosoma brucei, which is transmitted to mammals via the bite of infected tsetse flies. The disease manifests in two stages: the hemolymphatic stage and the meningoencephalitic stage. In the latter stage, it invades the Central Nervous System (CNS) and can be fatal if left untreated. It is caused by morphologically indistinguishable species of Trypanosoma brucei in both humans and animals, where in humans it is known as …

Chromosome Evolution Model Reveals Hidden Variation In Karyotype-Driven Speciation In Ferns, Thomas Buchloh

All Theses

Because karyotype change commonly generates reproductive isolation between diverging species, rapid karyotype evolution, like that seen in plants, may increase the total rate of diversification. However, few studies have investigated this predicted relationship. Tests of this prediction have identified a positive correlation between the rate of karyotype change (specifically whole genome duplications) and diversification, but tests have been restricted to relatively small and young clades. Fortunately, novel macroevolutionary models have recently become available to investigate patterns of karyotype evolution in large phylogenies, providing new opportunity to investigate variation in karyotype driven diversification. Ferns are one of the most karyotype rich …

The Roles Of Rnt1 And Putative Endoribonucleases In Eukaryotic Mrna Degradation, Lee-Ann Notice-Sarpaning

Dissertations and Theses (Open Access)

Endoribonucleases initiate degradation by cleaving RNAs internally. Mutations in these enzymes have been shown to cause diseases such as cancer, developmental disorders, and neurodegenerative diseases. Yet, eukaryotic endoribonucleases have not been well studied, especially with regard to their role in nuclear mRNA degradation. Rnt1 is a Saccharomyces cerevisiae (budding yeast) nuclear endoribonuclease and homolog of human Drosha with well-characterized roles in the processing of ncRNAs. The enzyme recognizes and cleaves double-stranded RNA stems containing a terminal tetraloop with an AGNN consensus sequence. However, the scope and consequence of its function in mRNA degradation has heretofore been unclear. Previous studies have …

Evaluating Cancer Rates, Cancer Types, And Variant Hotspots Between Different Races And Ethnicities In Individuals With Li-Fraumeni Syndrome, Hillary Esplen

Dissertations and Theses (Open Access)

Li Fraumeni Syndrome (LFS) is a cancer predisposition syndrome that increases the risk for numerous cancer types in both children and adults. In the general population, incidence rates for various cancer types differ among races and ethnicities. Although a few germline TP53 pathogenic/likely pathogenic (P/LP) variants in those with LFS have been studied and associated with specific populations, such as the South and Southeast Brazil founder variant, p.Arg337His, there still lacks research on the variable expressivity of cancers within the LFS population based on specific variant, race and/or ethnicity. This study aims to describe the specific TP53 germline variants, the …

Elucidating The Multi-Omics Of Early-Onset Colorectal Cancer, Jumanah Alshenaifi

Dissertations and Theses (Open Access)

The incidence and mortality rates of sporadic early-onset colorectal cancer have increased in recent decades, but there is no clear etiological basis for this trend. EOCRC is commonly defined as colon and rectal cancers diagnosed before the age of 50 years. The rising incidence of EOCRC has made it the second most common cancer and the third leading cause of cancer death in this age group. The rising incidence of EOCRC is also documented internationally in more than 20 countries across different continents. Clinically, EOCRC has a distinct, more aggressive clinical profile than LOCRC. While approximately 15% of EOCRC cases …

Impact Of Personal And Family History Of Huntington's Disease On The Decision And Ability To Obtain Life, Long-Term Care, And Disability Insurance, Karli Livingston

Dissertations and Theses (Open Access)

Huntington’s disease (HD) is an inherited, neurodegenerative condition characterized by a clinical triad of motor, cognitive, and psychiatric symptoms. Individuals diagnosed with HD manifest characteristic symptoms of the disease including motor and cognitive changes, and they may or may not have undergone genetic testing to confirm the diagnosis. Individuals at-risk for HD are those who have not yet undergone genetic testing for HD, but have a first- or second- degree relative diagnosed with the disease. Genetic testing for HD is categorized into two forms: predictive and confirmatory. However, many individuals choose not to pursue testing due to a fear of …

The Influence Of Scientific, Genetic, And Health Literacy On Carrier Screening Decision-Making, Brenna D. Albracht

Dissertations and Theses (Open Access)

For those wishing to assess their reproductive risks and make informed decisions in their reproductive planning, carrier screening for autosomal recessive and X-linked conditions, as well as cell-free DNA (cfDNA) screening for aneuploidy, are recommended during pregnancy. Despite similarities in purpose, sample requirements, insurance coverage, and safety, a lower percentage of individuals elect carrier screening than cfDNA screening, suggesting there may be a disconnect in what patients perceive as valuable information for their pregnancy. Previous studies have attempted to explain the factors associated with carrier screening uptake or decline; however, no models have yet accounted for a patient’s literacy level …

"Magic Computer In The Sky" - Participant Perspectives On Control And The Genetic Counseling Admissions Match, Jessica Clark

Dissertations and Theses (Open Access)

Since the 2018 admissions cycle, genetic counseling graduate programs in North America have utilized the Genetic Counseling Admissions Match (GCAM), a Match algorithm to place applicants. While a study prior to implementation found that most students were uninterested in a Match due to concerns of control, there has been no investigation into matched applicants’ experiences since its inception. A mixed-methods study explored the experiences and perceptions of control of genetic counselors and genetic counseling (GC) students who entered a program following the GCAM. An anonymous survey documenting GCAM experience and a validated measure for locus of control (LOC) was disseminated …

Evaluating Triage To Genetic Counseling Using An Online Reproductive Genetics Module, Grace Ra

Dissertations and Theses (Open Access)

The American College of Obstetricians and Gynecologists recommends genetic screening for all pregnant women. As clinical recommendations broaden and demand for prenatal screening increases, obstetric practitioners report time constraints and lack of genetics knowledge as challenges to providing sufficient pretest education. These challenges in offering routine screening are further compounded by the inequities in access to genetic counseling and testing. Thus, alternative education and service delivery models have emerged to meet the demands for prenatal genetics education and help mitigate challenges surrounding access. At UTHealth Houston, an online triage and education module, the Prenatal Genetics Education Program (PGEP), was created …

Intraspecific Genetic Variation In Green Salamanders (Aneides Aeneus) At Bays Mountain Park, Brianna Drake

Electronic Theses and Dissertations

Accurate taxonomy is crucial for conserving vulnerable cryptic species like the green salamander (Aneides aeneus) in the Southern Appalachian Mountains. Prior studies identified three distinct lineages within the A. aeneus complex: Northern Appalachians, Southern Appalachians, and Blue-Ridge Escarpment. One previously collected sample indicated green salamanders in northeast Tennessee fit within the Northern lineage. The present study uses molecular data of A. aeneus at Bays Mountain Park (BMP) in Kingsport, Tennessee, to determine where the BMP population fits within these lineages. It was hypothesized that individuals from BMP belong in the northern lineage. Tail tips were collected from thirty-four …

Investigation Into Mycorrhizae Associated With Native Venus' Flytrap Root Tissue, Anna Carnaggio

Electronic Theses and Dissertations

Dionaea muscipula, a plant commonly known as the Venus' flytrap, is found native to the southeast corner of North Carolina and the northeast corner of South Carolina. Several populations of native Venus' flytraps are known to exist in the nutrient-poor peat bog conditions in and around Lewis Ocean Bay Heritage Preserve (LOBHP) in Northeastern South Carolina. Anthropogenic pressures in Horry County, specifically surrounding LOBHP, have resulted in a loss of habitat for several native and endangered species. As a result, conservation efforts are focused on relocating native Venus' flytraps into adjacent habitats to ensure survival. This is only a temporary …

A Stakeholder-Informed Conceptual Framework For Evaluating Genomics In Precision Oncology, Julie A. Wiedower

All Dissertations

This dissertation explores the value of genomic testing in precision oncology with an emphasis on how US payers conceptualize and prioritize elements of value. This research aims to address gaps in understanding payer perspectives and proposes a stakeholder-informed framework for evaluating genomic testing in oncology. To achieve this aim, the presented research investigates payer perspectives, value-based cancer care priorities, and the conceptual understanding of the value of a genetic diagnosis to establish a framework for value with the payer audience in mind. Chapter 1 outlines relevant background information relating to the genomic revolution and challenges in translating genomic testing technologies …

The Genomic Landscape And Prognostic Impact Of Kras, Stk11, And Smarca4 Mutations And Co-Mutations On Survival Outcomes In Non-Small Cell Lung Cancer, Peter Manolakos

All Dissertations

Non-small lung cancer (NSCLC) accounts for 85% of lung cancer cases, and Kirsten rat sarcoma viral oncogene homolog (KRAS), Serine/Threonine Kinase 11 (STK11), and SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member 4 (SMARCA4) mutations and co-mutations have been increasingly recognized for their potential prognostic significance. However, clear knowledge gaps remain regarding which treatments should be selected for patients who present clinically with KRAS/STK11 or KRAS/SMARCA4 co-mutations, as outlined in Chapter 1. Despite significant clinical development advancements in immunotherapy and targeted therapy, a deeper understanding of the influence of these genomic …

Perspectives On Clinical Oncogenomics: Secondary Germline Variants Associated With Tumor Genomic Profiling In Community Cancer Care And Advanced Practitioner Oncogenomic Proficiency, Sarah Moncado

All Dissertations

Precision medicine in oncology is defined by the sequencing of tumor genomic variants that can be used to identify targeted treatment for patients. Secondary pathogenic and likely pathogenic germline variants (P/LPGVs) can incidentally be detected on tumor genomic profiling (TGP). With the rise in precision medicine over the past 15 years, secondary P/LPGVs on TGP have been an increasingly important clinical issue. However, there are factors that can lead to misidentification and underreporting of P/LPGVs. Germane to this clinical practice issue is healthcare provider oncogenomic literacy and proficiency.

A scoping review was conducted to evaluate the variability of the prevalence …

Crispr-Cas9 Integration Of Salmon Elovl2 In Zebrafish Enhances Lc-Pufa Biosynthesis And Growth Across Diets, Waleed Sami J. Al-Bachry

Graduate Theses and Dissertations

Fish are a rich source of EPA and DHA, which are well-known long-chain polyunsaturated fatty acids (LC-PUFAs). The sustainable production of these essential fatty acids poses significant challenges, mainly due to our dependence on marine fish and certain nuts. CRISPR-Cas system was utilized to insert the elongation of long-chain fatty acids-like2 (Elovl2) gene from Salmo salar into Danio rerio. Elovl2 was introduced at 10-15-minute post-fertilization, and successful integration confirmed by PCR genotyping, sequencing and expression of EGFP. Approximately 67% of injected embryos successfully exhibited EGFP and sequence results verified the gene integration of Salmo salar Elovl2 at the first start …

Developing A Small Molecule To Inhibit Hsf1 Expression In Cancer And Evaluating Natural Genetic Variation In Small Molecule Toxicity., Michaela Kendal Foley

Theses and Dissertations

Each year cancer affects nearly 20 million people worldwide and genetic differences across populations can impact cancer onset and progression. Specifically, tumors with high levels of HSF1, the master regulator of the cytoprotective heat shock response (HSR), are correlated with poor patient outcomes in multiple cancers such as prostate, breast, and melanoma. Subsequently, the development of pharmacological inhibitors of HSF1 represents a promising strategy for anticancer therapeutics. Using a luciferase-based transcriptional reporter, two small molecule libraries were screened for inhibitors of HSF1 expression in human embryonic kidney cells, yielding ten compounds that decrease HSF1 expression. To identify if cancer lines …

Gene Expression And Transfection Of C15orf57 In Chicken Show Clear Correlation To The Function Of The Ap2 Complex, E. Ashton Magdich

Graduate Theses and Dissertations

Discovering the functions of functionally unknown genes has made a huge impact on biological understanding including poultry species. In this thesis, C15orf57 (or C5H15orf57, chicken chromosome 5 human ortholog H15 open reading frame 57), was studied to understand its genetic characteristics and function. Chapter one is literature reviews on annotation of genes, the gene information on C15orf57, the importance of characterizing unknown genes in the genome, and what is known now about C15orf57. The Chapter 2 is for the structural characterization of C15orf57, gene expression of C15orf57 in various organ tissues using the qPCR method and effect of overexpression of …

Gonadal Absence Of Ceh-22: Degradation Of Ceh-22 In The Gonads Of Caenorhabditis Elegans, Andreya C. White

Undergraduate Theses

The reproductive system of hermaphrodite Caenorhabditis elegans (C. elegans) comprises two gonadal arms, each with a terminating distal tip cell (DTC), connected by a common uterus. The DTC has two functions: leader and niche. In C. elegans, ceh-22/nkx2,5 has been found to work together with Wnt signaling to determine the fates of the DTC (Lam et al., 2006). This is an indication that ceh-22 aids in the specification of DTCs. Our research aims to determine the specific function of ceh-22 in the gonad of both male and hermaphrodite C. elegans. This will be accomplished by observing …

Degradation Of Vascular Networks In A Huvec Model Of Dm1, Bonnie E. Butler

Departmental Honors & Graduate Capstone Projects

Myotonic dystrophy type 1 (DM1) is a genetic disease that causes muscle wasting and affects multiple organ systems. DM1 is caused by expanded CTG repeats in the 3’ untranslated region of the dystrophia myotonica protein kinase (DMPK) gene (Harper, 2001). Skeletal muscle relies on capillaries for nutrient delivery and waste clearance (Olfert, 2016). Skeletal muscle and capillaries communicate via a variety of chemicals, including PDGF-BB which both skeletal muscle and endothelial cells secrete and have receptors for (Hamaguchi, 2023). Platelet derived growth factor receptor β (PDGFRβ), when bound to platelet derived growth factor BB (PDGF-BB), induces angiogenesis (Wang, 2012). In …

The Role And Expression Of Pros-1 In The C. Elegans Gonad, Brandon W. Thomas, Mary B. Kroetz, Roberta Challener

Undergraduate Theses

The nematode, formally known as Caenorhabditis elegans, has served as an excellent model organism in understanding fundamental biological processes, including those governed by conserved genes like pros-1. pros-1 is partially responsible for the formation of tubular structures within the organism. Glial cells and excretory canals are both examples of tubular structures governed by pros-1. pros-1 orchestrates the embryonic development of these cell types by modulating cell proliferation and differentiation, thus ensuring proper morphogenesis and organogenesis. Its regulatory influence likely extends beyond embryogenesis, potentially affecting reproductive processes as well. Furthermore, the evolutionary conservation of pros-1 underscores its significance …

Below-Ground Carbon Gradients Surrounding Saskatchewan's Native Agricultural Copses, Andrea V. Cline, Colin P. Laroque

Aspen Bibliography

As carbon markets develop, understanding the carbon storage capabilities of agricultural land is imperative to maximizing carbon storage. Ecosystems store two-thirds of their carbon below ground. Shrubland and shelterbelt carbon storage have been well documented in agricultural settings, yet little is known about the carbon stored under the native woody vegetation scattered across the Prairies. This study aims to be the first to quantify the below-ground carbon under and around these native trembling aspen (Populus tremuloides) copses in the Canadian Prairies. For this study, the leaf, fibric, humic layer (LFH) and soil samples up to 60cm were collected …

Investigating Genetic Regulators Of Crystal Cell Development In Drosophila Melanogaster, Andrea Feria, Nyla Walbrook, Anisa Turaeva, Rebecca Spokony

Publications and Research

Crystal cells, a subset of Drosophila melanogaster hemocytes, are important for melanization, a crucial immune response. While the genetic regulation of crystal cell develop remains incompletely understood, this study investigates the functions of five candidate genes: ACXB, ACXA, Gp210, CG4390, and Cyp4s3; identidied through previous genome-wide association studies. Using the Gal4/UAS system along with RNA interference (RNAi), we exclusively knocked down each gene in third instar larvae and quantified crystal cell populations following heat shock-induced melanization. Our results imply that the knockdown of ACXB and ACXA significantly increased crystal cell counts in both sexes, suggesting these genes either act as …

Args & Chronic Disease: How Antibiotic Resistance Genes Impact The Progression Of Type Ii Diabetes, Paige Imperato

Thinking Matters Symposium

Antibiotics are typically offered to patients with no warning of long-term consequences, though increasing evidence suggests this may not be entirely true. When antibiotics enter the body, they kill both good and bad bacterial populations in the gut - collectively known as the human microbiome. Repeated use of these drugs encourages mutations in this bacterial population [2]. This leads to the creation of antibiotic-resistant genes (ARGs) in antibiotic resistant bacteria (ARB). The causal relationship between antibiotic use and bacterial resistance is well established. However, recent research suggests a newly discovered relationship between the presence of specific ARGs in the microbiome …

A Natural Short Sleep Mutation Promotes Longevity Through Mitochondrial Respiration In Drosophila, Pritika Pandey

LSU Doctoral Dissertations

Aging is an irreversible process characterized by progressive physiological decline and an increased risk of metabolic disorders, cognitive impairment, cardiovascular diseases, and neurodegeneration. Disruptions to the circadian clock—whether due to genetic mutations or behavioral factors—accelerate aging and age-related pathologies, highlighting a strong link between circadian regulation and longevity. However, certain individuals harbor a dec2^P384R mutation, which enables natural short sleep without the detrimental effects of chronic sleep deprivation. This suggests that these individuals have evolved adaptations that activate pro-health pathways, allowing them to function optimally with reduced sleep. To investigate the genetic mechanisms underlying these changes, we developed a …

Highly Targeted Metabolomics Coupled With Gene Expression Analysis By Rt–Qpcr Improves Beef Separation Based On Grass, Grain, Or Grape Supplemented Diet, Lucas Krusinski, Chloe Castanon, Rosalee S. Hellberg, Isabella C. F. Maciel, Muhammad Ahsin, Stephan Van Vliet, Jason E. Rowntree, Jennifer I. Fenton

Food Science Faculty Articles and Research

The objective of this study was to use a multi-omics (i.e., gene expression quantification, metabolomics, and fatty acid [FA] profiling) approach to separate and authenticate beef from three different dietary groups. In this 2-year study, Red Angus steers (n = 54) were randomly allocated to one of three treatments: (1) complex biodiverse pasture (GRASS), (2) total mixed ration (TMR) in feedlot (GRAIN), or (3) TMR in feedlot supplemented with 5% (dry matter) grapeseed extract for the last 30 days (GRAPE). FAs were measured by gas chromatography-mass spectrometry (GC–MS), secondary metabolites were identified using ultra-high-performance liquid chromatography tandem mass spectrometry …

Functional Protein Biomarkers Based On Distributions Of Expression Levels In Single-Cell Imaging Data, Misung Yi, Tingting Zhan, Hallgeir Rui, Inna Chervoneva

Department of Pharmacology, Physiology, and Cancer Biology Faculty Papers

MOTIVATION: The intra-tumor heterogeneity of protein expression is well recognized and may provide important information for cancer prognosis and predicting treatment responses. Analytic methods that account for spatial heterogeneity remain methodologically complex and computationally demanding for single-cell protein expression. For many functional proteins, single-cell expressions vary independently of spatial localization in a substantial proportion of the tumor tissues, and incorporation of spatial information may not affect the prognostic value of such protein biomarkers.

RESULTS: We developed a new framework for using the distributions of functional single-cell protein expression levels as cancer biomarkers. The quantile functions of single-cell expressions are used …