Life Sciences Commons^™

An Investigation Of Epigenetic Mechanisms Driving The Biology Of Head And Neck Squamous Cell Carcinoma, Scot Carson Callahan

Dissertations & Theses (Open Access)

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common cancer worldwide and is associated with significant morbidity and mortality. To date, the majority of work in the field has focused on genomic alterations such as mutations and copy number alterations. However, the clinical success of targeted therapies that exploit known genomic alterations, such as EGFR mutations, has remained mixed. Over the past decade, the importance of epigenetic regulators has come to the forefront, with the realization that many of these genes are mutated in cancer. Despite this realization, the role of epigenetics in regulating tumorigenesis, progression and …

Understanding The Genomic Influence And Virulence Capabilities Of Environmentally Isolated Vibrios, Shannon Elizabeth Pipes

Theses and Dissertations

The genus Vibrio consists of Gram-negative bacteria that possess a curved rod shape and are routinely isolated from estuarine and coastal salt water. Vibrio cholerae, Vibrio parahaemolyticus, and Vibrio vulnificus are the major three species that contribute to human disease worldwide, and a variety of other Vibrio species contribute to persistent problems in the aquaculture and fishing industries. The CDC estimates that vibrios cause 80,000 cases of disease each year in the United States alone, however, this number is thought to be underestimated, since some disease is only self-limiting, meaning patients may not seek medical treatment and have …

The Influence Of Climate Change On The Ecology Of The Arctic Ground Squirrel In Denali National Park, Ak., Nigel A. Golden

Doctoral Dissertations

This dissertation research focuses on the ecology of the Arctic ground squirrel (Urocitellus parryii) in Denali National Park and Preserve, AK. The Arctic ground squirrels is a species of interest for monitoring efforts under the National Park Services’ Vital Signs Monitoring Program under the Vital Signs Monitoring program. The focus of this program is to monitor what is considered to be the most significant indicators of ecological conditions of the specific park resources that are of the greatest concern. The CAKN designated the Arctic ground squirrel (Urocitellus parryii) as one indicator species of park ecosystems. Despite being easy to observe …

Genomic Organization And Expression Of The Wc1 Hybrid Coreceptor And Pattern Recognition Receptor On Porcine Gamma Delta T Cells, Lauren Le Page

Doctoral Dissertations

gd T cells are a crucial component of the immune response to a number of increasingly relevant and largely zoonotic pathogens to which efficacious vaccination is lacking. In ruminants and swine, gd T cells represent a major population of peripheral blood and epithelial tissue-resident lymphocytes. gdT cells respond to both protein and non-protein antigens independently of MHC presentation and possess immunological memory. Upon activation, gamma delta T cells illicit a variety of effector functions and play an indispensable role of orchestrating the downstream immune response. These characteristics make gamma delta T cells a promising candidate for recruitment by vaccination, however, …

Single Cell Lineage Tracing Reveals Mechanisms Of Tumor Initiation And Chemoresistance In Small Cell Lung Cancer, Hannah Wollenzien

Dissertations and Theses

Small Cell Lung Cancer (SCLC) is a devastating disease characterized by a very low two-year survival rate and almost universal acquisition of chemoresistance. Nearly all patients have tumors driven by functional inactivation of the tumor suppressors Rb and p53, but despite the uniform origins of this tumor, not all patients are genetically or phenotypically identical. SCLC can be subtyped into four unique molecular subtypes, determined by the expression of ASCL1, NEUROD1, POU2F3, or YAP1. These subtypes are plastic, and subtype switching after chemotherapy has been documented. Without the understanding of how tumor heterogeneity arises, we cannot solve the challenge of …

Population Genomics Of Redbreast Sunfish (Lepomis Auritus): Exploring Gene Flow And Local Adaptation In A Widely Distributed Freshwater Fish, Garret J. Strickland

Electronic Theses and Dissertations

Little information is available concerning the distribution of genetic diversity in non-salmonid, non-imperiled, freshwater fish. In order to fill in this knowledge gap, I conducted a population genomics survey in Redbreast Sunfish (Lepomis auritus; RBS), a widespread, generalist species distributed along the Atlantic slope rivers of eastern North America. I sampled four basins (ACF, Savannah, Roanoke, and James) at eight sites each with a factorial experimental design. Sites were distributed among coastal plain, Piedmont, or mountain ecoregions in order to capture the greatest range of environmental states experienced by RBS, with the intention of finding evidence for local adaptation to …

Genomic Epidemiology Of Clinical Salmonella Enterica In New Hampshire, 2017-2020, Madison R. Turcotte

Legacy Theses & Dissertations (2009 - 2024)

Antimicrobial resistance in Salmonella enterica remains a challenging public health threat. We aim to characterize the population structure and evolutionary history of 394 genomes of S. enterica isolates recovered from human clinical cases in New Hampshire, USA from 2017 to 2020. The population is phylogenetically diverse, consisting of 78 STs and 67 serotypes. We detected 61 genes associated with resistance to14 different antimicrobial classes. Rather than a single multidrug resistant clone expanding in the state, we found multiple lineages carrying different combinations of independently acquired resistance determinants. New or emerging lineages can therefore rapidly spread over relatively short timeframes. In …

Applying Conservation Genomic Techniques To Guide Management Of The Reticulated Flatwoods Salamander (Ambystoma Bishopi), Miranda Gaupp

Electronic Theses and Dissertations

The Reticulated flatwoods salamander (Ambystoma bishopi) is a federally endangered amphibian endemic to the longleaf-pine ecosystem of the southeastern U.S. This study used analyses of single-nucleotide polymorphism (SNP) data, collected from 2,255 unique individuals across 5 breeding seasons, spread across the known extant range of A. bishopi, to characterize the genetic diversity and demographics of populations, genetic relationships among populations, and patterns and spatial extents of gene flow, and to evaluate potential effects of management on A. bishopi’s resiliency. Population structure was strongly hierarchical, with individual breeding ponds (n = 38) acting as semi-connected subpopulations …

Quantifying Contributions Of Climate, Geography, And Gene Flow To Divergence: A Case Study For Three North American Pines, Constance E. Bolte

Theses and Dissertations

Long-lived species of trees, especially conifers, often display weak patterns of reproductive isolation, but clear patterns of local adaptation and phenotypic divergence. Discovering the evolutionary history of these patterns is paramount to a generalized understanding of speciation and the processes that confer population persistence versus those that compromise adaptive potential under rapidly changing environments. Forest trees have long generation times and low migratory potential making them especially vulnerable to population fragmentation and reductions of genetic diversity due to insufficient tracking of niche optima and adaptational lags. Within clades of the genus Pinus, evolutionary histories appear to be riddled with hybridization …

Examination Of Common And Rare Variant Genetic Architecture Of Psychiatric Disorders, Mohammad Ahangari

Theses and Dissertations

Psychiatric disorders are often heterogenous in their manifestation and genome-wide association studies have identified many common risk variants involved in their polygenic architectures with varying degrees of pleiotropy. In recent years, large-scale biobanks have also begun sequencing the genome of their participants to elucidate the role of rare risk variation in the genetic architecture of complex phenotypes, including psychiatric traits. This dissertation sought to better understand the role of both common and rare risk variation in the genetic architecture of psychiatric disorders with a particular focus on schizophrenia and alcohol problems. In the first three analyses, we focused on characterizing …

Landscape Population And Evolutionary Genomics Of Several Closely Related Species Of Mallard-Like Ducks, Joshua Brown

Open Access Theses & Dissertations

Divergence and speciation proceed through three major evolutionary forces (i.e., selection, genetic drift, and gene flow) that are often spatially and temporally heterogeneous across the landscape. Moreover, these forces can have differing but subtle effects within the genomes of diverging taxa, and therefore, disentangling the effects of these evolutionary mechanisms throughout the speciation process can be challenging. Here, I use a recent species radiation, the mallard complex, to investigate how strong, yet varied, evolutionary pressures influence the speciation process. The mallard complex consists of 14 mallard-like waterfowl species around the world that have some of the highest rates of hybridization …

Impact Of Intratumor Heterogeneity And The Tumor Microenvironment In Shaping Tumor Evolution And Response To Therapy, Akash Mitra

Dissertations & Theses (Open Access)

Intratumor heterogeneity (ITH) is a crucial challenge in cancer treatment. The genotypic and phenotypic heterogeneity underlying diverse cancer types leads to subclonal variation, which may result in mixed or failed response to therapy. The heterogeneity at the tumor level, along with the tumor microenvironment (TME), often shapes tumor evolution and ultimately clinical outcome. Given that modern treatment paradigms increasingly expose patients with metastatic disease to multiple treatment modalities through the course of their disease, there exists a need to characterize robust and predictive biomarkers of response to therapy. In order to accurately characterize tumor evolution, we need to account for …

Applications Of And Algorithms For Genome Assembly And Genomic Analyses With An Emphasis On Marine Teleosts, Brandon D. Pickett

Theses and Dissertations

The burgeoning frequency of genome sequencing in recent years is a testament to both the improvements in sequencing technologies and the utility of genomic analyses for biological discovery. The rapid proliferation in technological advancements and availability of complementary data types and techniques has obfuscated the optimal process of genome assembly and raised the barrier to entry to unprecedented levels. In this dissertation, we describe the genome assemblies performed for several marine teleosts and discuss the algorithms and applications required for genome assembly, including some of our specific contributions to the genome assembly and annotation space. In Chapter 1 and Chapter …

Analysis Of Structural Variation And Mtdna Copy Number In Finns, Liron Ganel

Arts & Sciences Electronic Theses and Dissertations

Cardiovascular disease (CVD) is a complex disease responsible for more deaths worldwide than any other cause according to the World Health Organization. Genetic association studies for CVD and related risk factors have successfully identified hundreds of loci associated with these complex diseases and traits, although much of their heritability remains unexplained. Structural variants (SVs) - including insertions, deletions, duplications, and inversions - are an understudied class of genomic variation that have the potential to explain much of the missing heritability of CVD and other complex traits. Here, we discuss advances emerging from the study of SVs in the context of …

Development Of In-Silico Pipelines For Identification And Characterization Of Biomarker Panels And Therapeutic Interventions In Gastro-Intestinal (Gi) Cancers, Pranita Atri

Theses & Dissertations

Gastro-intestinal (GI) malignancies, including gastric, colorectal, and pancreatic cancers, have maintained their high overall mortality due to a lack of prognostic and diagnostic biomarkers and potential therapeutic modalities. While efforts have been made to improve both early detection and therapeutic interventions in these cancers, failure of conventional approaches have proven to be a big challenge, and alternate approaches are needed. Computational biology approaches owing to lesser time and more per target success rate offer a unique solution here. The current study explored the use of computational biology techniques to study the various aspects relating to GI malignancies. First, we sought …

Involvement Of The Ino80 Chromatin Remodeling Complex In Cell Division And Genomic Stability, Ethan Chen

Biomedical Engineering Undergraduate Honors Theses

Cell division is a vital biological process for growth and development in both single and multi-cellular organisms—whereby the cell must duplicate its organelles and genome in entirety and appropriately distribute the copied contents to the daughter cells. Cells undergo a cycle of two distinct phases: interphase and mitosis. During interphase, the cell replicates its genomic DNA (in the form of chromosomes) located within the nucleus. DNA replication is carried out in a euchromatin state, where the chromosome structure is loose and easily accessible by DNA polymerase and other replication enzymes. Upon the completion of replication, chromatin is condensed into highly …

Genetics Of Pediatric Musculoskeletal Disorders, Lilian Antunes

Arts & Sciences Electronic Theses and Dissertations

Pediatric musculoskeletal disorders are an extremely broad category of diseases that are often inherited. While individually rare, collectively these disorders are common, affecting around 3% of live births in the US. Despite the mounting clinical and molecular evidence for a genetic etiology, the cause for many patients with pediatric musculoskeletal disorders remain largely unknown. Major challenges in rare pediatric diseases include recruiting large numbers of patients and determining the significance and functional impacts of variants associated with disease within individuals or families. Whole exome sequencing (WES) is a powerful tool to identify coding variants that are associated with rare pediatric …

Chloroplast Genome Evolution In The Klebsormidiophyceae And Streptofilum, Sarah Glass

Theses

The Klebsormidiophyceae are a class of green microalgae found globally in both freshwater and terrestrial habitats. Morphology-based classification schemes of this class have been shown to be insufficient, particularly due to the simple morphology of these algae, the tendency of morphology to vary in culture versus in field conditions, and rampant morphological homoplasy. Molecular studies revealing cryptic diversity have renewed interest in this group. We sequenced the complete chloroplast genomes of taxa in the Klebsormidiophyceae representing the known taxonomic breadth of this class, as well as the chloroplast genomes of three strains of Streptofilum, a recently discovered algal lineage …

Comparative Conservation Genomics Of A Suite Of Imperiled Freshwater Mussels, Scott C. Meyer

Electronic Theses and Dissertations

Maintenance of genetic diversity is a critical component to the management and recovery of imperiled species. By ensuring that a species’ genetic diversity is maintained, issues like inbreeding depression and loss of local adaptation can be prevented. However, the genetic diversity of many species are not well-characterized, and the factors that influence a species’ genetic diversity are often not well understood. In the case of imperiled unionid freshwater mussels, it is important to conduct conservation genetic assessments to aid in their management and preserve genetic diversity. This is the first study to conduct a comparative conservation genomic assessment for eight …

Transcriptional Programming By Thyroid Hormone Receptor Beta Maintains Normal Cell Identity And Suppresses Tumor Growth, Noelle Elizabeth Gillis

Graduate College Dissertations and Theses

The overall incidence of thyroid cancer has more than tripled over the past several decades, as has aggressive disease and mortality. The direct relationship between thyroid disease, thyroid hormone levels, and development of thyroid cancer is incomplete. Recent meta-analyses have indicated a higher risk of thyroid cancer for patients with thyroid diseases that reflect an altered thyroid-pituitary signaling axis, which can have profound impacts on the physiology of the thyroid gland. These largely unanswered questions regarding altered thyroid hormone signaling and its consequences for thyroid tumor growth present a significant clinical challenge. This dilemma may come from a lack of …

Characterization Of Higher Order Chromatin Structures And Chromatin States In Cell Models Of Human Herpesvirus Infection, Michael Mariani

Graduate College Dissertations and Theses

Human herpesviruses are ubiquitous pathogens worldwide with 90% of the global population infected with one or more Human herpesviruses (HHV’s) by adulthood. All herpesviruses have three unique life cycle stages. Upon resolution of a primary acute stage infection, they can establish a latent stage infection within the host cell nucleus. This stage is characterized primarily by transcriptional quiescence of the viral genome. Specific physiological conditions (e.g., cell stress) can cause the latent virus to enter the reactivation stage, often many years after resolution of the acute infection, in which the virus becomes replicationally active again. HHV’s are known to cause …

The Impacts Of External Patient Variables On Gene Expression Profiles Of Lung Adenocarcinomas, Michael Madsen

CMC Senior Theses

The search for improvements to detection and treatment of cancers is a paramount goal for all of medicine. The most important step for oncological research is to expand the knowledge base of the genetic characteristics and abnormalities that give rise to cancer. In our present day, one of the most pressing and deadly forms of cancer is that of the lung, with lung adenocarcinomas being the most prevalent variation of the disease. Improving our cancer genomic insight can provide the seedings for improved cancer detection, novel cancer treatment, and serve as a guide for avenues to explore with future oncological …

Molecular Responses To Catastrophic Molting In A Wild Marine Mammal, Anna Keith

University of the Pacific Theses and Dissertations

While most mammals shed their hair and skin either continuously or seasonally, northern elephant seals (Mirounga angustirostris) undergo an annual catastrophic molt, in which they shed their entire fur and underlying skin layer in the span of just three weeks. Due to the energetic and thermoregulatory constraints of molting and the large distances between their coastal rookeries and foraging grounds, elephant seals must remain on land and fast for the duration of their molt. Previous studies of molting northern elephant seals have examined endocrine and metabolic adjustments to fasting, but not the molecular processes underlying molting. We examined changes in …

Composition And Homology In The Taxonomic Classification Of Escherichia Coli, Tanya Irani

Theses and Dissertations (Comprehensive)

As new techniques have been introduced, specifically the possibility of complete genome sequencing, better methods of defining bacterial species have also been proposed. One of the most recently proposed methods, using bioinformatic techniques, is to calculate the average nucleotide identity (ANI) between the homologous genome segments of different isolates. Another method for species discrimination that has been tested successfully is the similarity of DNA compositional signatures. However, in a recent update, DNA signatures split the available Escherichia coli complete genomes into three groups. To check if this result was consistent with such genomes belonging to different species, we tested methods …

3d Genome Architecture Under Stress: A Survey Of Ionizing Radiation, Progeria, And Osmotic Stress, Jacob Tyler Sanders

Doctoral Dissertations

The human nucleus contains 2 meters of DNA which is intricately folded into a three-dimensional (3D) structure. It has become increasingly clear that this 3D structure plays an important role in the expression of genes. Proper gene expression is necessary for cellular homeostasis, cell state, and response to environmental/physical perturbations. Faithful repair of damage DNA damage is necessary to prevent genomic aberrations, such as translocations, which may lead to misregulation of gene expression. Hi-C, a sequencing technique that labels proximal chromatin interactions, provides a clearer picture of how the genome is spatially organized within the nucleus. Here, we discuss the …

Investigation Of Proliferation Suppressors In Genetic Fitness Screens, Walter Frank Lenoir Iv

Dissertations & Theses (Open Access)

Innovation of CRISPR gene-editing technology has provided scientists genome manipulation tools that allowed rapid advancement of scientific capabilities and thus improved our ability to systematically study mammalian genetic functional profiles. Genome-wide CRISPR knockout screens conducted in collections of human cell lines can knock out genes at multiple loci, and have provided new insights into functional roles for independent genes. This method has launched massive efforts in looking across genetic backgrounds for context specific genetic vulnerabilities within cancer. Much of the research effort thus far has been spent on optimizing phenotype distinctions between essential, genes required for cell fitness, and non-essential, …

Molecular Genetic Analysis Of Drought Resistance And Productivity Traits Of Rice Genotypes, Yheni Dwiningsih

Graduate Theses and Dissertations

Rice (Oryza sativa L.) is the staple food for a majority of the world’s population, and uses 30% of the global fresh water during its life cycle. Drought at the reproductive stage is the most important abiotic stress factor limiting grain yield. The United States is the third largest exporter of rice, and Arkansas is the top rice-producing state. The Arkansas rice-growing region in the Lower Mississippi belt is among the 10 areas with the highest risk of water scarcity. Adapted U.S. rice cultivars were screened for drought resistant (DR) traits to find sources for breeding U.S. rice cultivars for …

Evolution Of Green Blood In New Guinea Lizards: Phylogenomics, Biogeography, And Comparative Genomics, Zachary Rodriguez

LSU Doctoral Dissertations

Non-model organisms with evolutionary novelties and complex distributions can provide valuable insight into the mechanisms underlying biological diversity. Green blood is one of the most unusual vertebrate physiologies and has repeatedly evolved in lizards from the megadiverse island of New Guinea. An unusually high concentration of the toxic green bile pigment biliverdin causes the green coloration of these lizards' blood, muscles, and bones. This dissertation uncovered the complex history of this novel trait (Chapter 2), identified protein-coding sequences that underlie green blood in lizards (Chapter 3), and explored evolutionary processes that drive genetic diversity in high-elevation lizards. To accurately trace …

Comparison Of Cpu And Parabricks Gpu Enabled Bioinformatics Software For High Throughput Clinical Genomic Applications, Stefano Rosati

Master's Theses (2009 -)

In recent years, high performance computing (HPC) has begun to revolutionize the architecture of software and servers to meet the ever-increasing demand for speed & efficiency. One of the ways this change is manifesting is the adoption of graphics processor units (GPUs). Used correctly, GPUS can increase throughput and decrease compute time for certain computational problems. Bioinformatics, an HPC dependent discipline, is no exception. As bioinformatics continues advance clinical care by sequencing patient’s DNA and RNA for diagnosis of diseases, there is an ever-increasing demand for faster data processing to improve clinical sequencing turnaround time. Parabricks, a GPU enabled bioinformatics …

A Mechanistic And Genomic Analysis Of Molluscum Contagiosum Virus Immune Evasion, Ian Benjamin Harvey

Arts & Sciences Electronic Theses and Dissertations

Molluscum contagiosum virus (MCV) is a common human-specific poxvirus with a proclivity for

infecting children and the immune-compromised. A characteristic MCV infection is restricted to

the epidermal layers of the skin and can persist for weeks to years in an otherwise healthy

individual. The high clinical burden of MCV is at odds with our limited knowledge regarding how

it successfully evades the human immune response, which is in part due to the lack of an animal

model or cell line to propagate the virus. Through this dissertation, we have uncovered and

characterized a novel mechanism by which MC80, a protein …