Biology Commons^™

Discerning Drivers Of Cancer: Computational Approaches To Somatic Exome Sequencing Data, Runjun Kumar

Arts & Sciences Graduate Student Theses and Dissertations

Paired tumor-normal sequencing of thousands of patient’s exomes has revealed millions of somatic mutations, but functional characterization and clinical decision making are stymied because biologically neutral ‘passenger’ mutations greatly outnumber pathogenic ‘driver’ mutations. Since most mutations will return negative results if tested, conventional resource-intensive experiments are reserved for mutations which are observed in multiple patients or rarer mutations found in well-established cancer genes. Most mutations are therefore never tested, diminishing the potential to discover new mechanisms of cancer development and treatment opportunities. Computational methods that reliably prioritize mutations for testing would greatly increase the translation of sequencing results to clinical …

Multi-Omics Portraits Of Cancer, Kuan-Lin Huang

Arts & Sciences Graduate Student Theses and Dissertations

Precision oncology demands accurate portrayal of a disease at all molecular levels. However, current large-scale studies of omics are often isolated by data types. I have been developing computational tools to conduct integrative analyses of omics data, identifying unique molecular etiology in each tumor. Particularly, this dissertation presents the following contributions to the computational omics of cancer: (1) uncovering the predisposition landscape in 33 cancers and how germline genome collaborates with somatic alterations in oncogenesis; (2) pioneering methods to combine genomic and proteomic data to identify treatment opportunities; and (3) revealing selective phosphorylation of kinase-substrate pairs. These findings advance our …

The Role Of Actr10 In Nervous System Development And Disease, Amy Herbert

Arts & Sciences Graduate Student Theses and Dissertations

The vertebrate nervous system requires myelinating glia for the fast propagation of action potentials, as well as for vital trophic support to axons. Myelinating glia produce myelin, which is a lipid-rich, multi-lamellar sheath that surrounds axons and allows for rapid electrical signaling. In the central nervous system (CNS), myelin is produced by oligodendrocytes, while in the peripheral nervous system (PNS), Schwann cells perform this function. Although glia have historically been understudied compared to neurons, recent research has uncovered critical roles for glia in nervous system development and disease. Disruption to myelin or to the glial cells that generate myelin can …

The Ugly Sequestosome1:The Role Of P62/Sqstm1 In Autophagy And Multisystem Proteinopathy, Eugene Lee

Arts & Sciences Graduate Student Theses and Dissertations

Multisystem proteinopathy (MSP) defines a spectrum of degenerative diseases unified by TDP-43 pathology that affect muscle, brain and bone. Mutations in several proteins (VCP, p62/SQSTM1, HNRNPA2B1, HNRNPA1) can all cause MSP via impairments in autophagic protein degradation (VCP and SQSTM1) or RNA granule dynamics (HNRNPA2B1 and HNRNPA1). Phenotypically, MSP mutations lead to variable penetrance of several phenotypes: Paget’s disease of the bone (PDB), rimmed vacuolar inclusion body myopathy (RV-IBM), amyotrophic lateral sclerosis (ALS) or frontotemporal dementia (FTD). However, how a same mutation of a protein can develop different diseases remains unclear. Understanding of p62/SQSTM1 (SQSTM1) function is critical to answer …

Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer

Arts & Sciences Graduate Student Theses and Dissertations

Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, which expands immune suppressive granulocytes and monocytes to create a protective tumor niche shielding even antigenic tumors. As myeloid cells and immune-stimulatory conventional dendritic cells (cDCs) are derived from the same progenitors, it is logical that tumor-induced myelopoiesis might also impact cDC development. The cDC subset cDC1 is marked by CD141 in humans and CD103 or CD8α in mice. cDC1s act by cross presenting antigen and activating CD8+ T cells. Given these functions, CD103+ cDC1s can support anti-tumor CD8+ T cell responses. However, CD103+ cDC1 numbers are …

Defining Neuronal Identity Using Microrna-Mediated Reprogramming, Matthew James Mccoy

Arts & Sciences Graduate Student Theses and Dissertations

Cell fate reprogramming is transforming our understanding of the establishment and maintenance of cellular identity. In addition, reprogramming holds great promise to model diseases affecting cell types that are prohibitively difficult to study, such as human neurons. Overexpression of the brain-enriched microRNAs (miRNAs), miR-9/9* and miR-124 (miR-9/9*-124) results in reprogramming human somatic cells into neurons and has recently been used to generate specific neuronal subtypes affected in neurodegenerative disorders. However, the mechanisms governing the ability of miR-9/9*-124 to generate alternative subtypes of neurons remained unknown. In this thesis, I report that overexpressing miR-9/9*-124 triggers reconfiguration of chromatin accessibility, DNA methylation, …

Innate Lymphoid Cells: Transcriptional Profiles And Cytokine Developmental Requirements, Michelle Lauren Robinette

Arts & Sciences Graduate Student Theses and Dissertations

Innate lymphoid cells (ILCs) are a recently discovered lineage of professional cytokine-producing cells that strikingly mirror T cells in transcriptional circuitry and effector functions, but derive from distinct progenitors and do not express recombined antigen-specific receptors. These cells include natural killer (NK) cells, which parallel cytotoxic CD8+ T cells, and three additional classes of ILCs enriched at mucosal surfaces that generate signature cytokines reminiscent of polarized CD4+ helper T cells subsets, called ILC1, ILC2, and ILC3. As ILCs have been implicated in the pathogenesis of colitis, cancer, allergy, and autoimmunity in both human and mouse, understanding the functional capacity of …

Sex Differences In Uropathogenic Escherichia Coli Urinary Tract Infection, Patrick David Olson

Arts & Sciences Graduate Student Theses and Dissertations

Urinary tract infections (UTIs) are among the most common bacterial infections which plague humans. Community-onset UTI is widely viewed as a disease only of women; indeed, its occurrence between 2 and 60 years of age is almost exclusive to females. However, the disease also affects substantial male patient populations, namely infants and the very elderly. While female cases of complicated and upper-tract UTI (pyelonephritis) outnumber male cases overall, men carry an increased risk of mortality from these infections. Sex differences in UTI epidemiology have heretofore been attributed almost entirely to anatomic and hygienic factors in females, including the permissiveness of …

Circadian Regulation Of Temozolomide Sensitivity In Glioblastoma, Emily A. Slat

Arts & Sciences Graduate Student Theses and Dissertations

The safety and efficacy of multiple cancer chemotherapeutics can vary as a function of when during the day they are delivered. This study aimed to improve the treatment of glioblastoma multiforme (GBM), the most common brain cancer, by testing the efficacy of the DNA alkylator Temozolomide (TMZ) on GBM in vitro and in vivo as a function of time of day. We found cell-intrinsic, daily rhythms in susceptibility of GBM tumor cells (mouse astrocytes deficient in NF1 and p53 signaling) to TMZ in vitro. The greatest TMZ-induced DNA damage response, activation of apoptosis and growth inhibition, occurred near the peak …

Deciphering Mechanisms Governing The Development Of The Rod Epigenome, Philip Andrew Ruzycki

Arts & Sciences Graduate Student Theses and Dissertations

Precisely coordinated expression of distinct sets of genes is essential for cellular development and function, especially in complex multicellular organisms. This regulation is achieved by the action of transcription factors (TF), proteins that bind specific genomic locations and alter the activity state and packaging of the DNA to promote or repress gene expression. However, while tremendous effort has defined networks of transcription factors that work together to drive specific phenotypes, little is known about their differential activity at the hundreds or thousands of sites where they bind. There are also many questions regarding the basic principles of the packaging of …

Characterizing The Role Of The T Cell Receptor Repertoire In T Cell Development And Function, Benjamin David Solomon

Arts & Sciences Graduate Student Theses and Dissertations

Expansion and memory of immune cells in response to stimulation of diversified antigen receptors is the hallmark of adaptive immunity. Here, we use antigen receptor sequencing and in vivo analysis of monoclonal cell populations to elucidate the development and function of two T cell populations: Foxp3+RORγt+ CD4+ T cells and γδ T cells. Foxp3+RORγt+ T cells have recently been characterized as an immunoregulatory population highly enriched in the colon lamina propria. However, their developmental origin and relation to RORγt- Treg and RORγt+ TH17 cells remains unclear. Here, we show that despite sharing a subset of TCR specificities with TH17 cells, …

Regulation Of Epithelial Proliferation And Migration By Apical-Basal Polarity Proteins, Gregory Vincent Schimizzi

Arts & Sciences Graduate Student Theses and Dissertations

Epithelial cells line all the outside surfaces of the body where they perform essential roles in maintaining homeostasis. In addition, epithelial tissues are implicated in many disease processes and are the most common tissue type to give rise to human cancer. Therefore, a thorough understanding of epithelial development and homeostasis has broad implications for understanding human development, health, and disease. The establishment and maintenance of apical-basal polarity is a defining characteristic and essential feature of functioning epithelia. Proper apical-basal polarity (ABP) is required for epithelial tissues to carry out their functions, which include absorption, secretion, barrier formation, and collective migration. …

Molecular Mediators Of Acute And Chronic Itch In Mouse And Human Sensory Neurons, Manouela Valtcheva

Arts & Sciences Graduate Student Theses and Dissertations

Itch is a distinct sensation that arises from the activation of small-diameter pruriceptive nerve fibers innervating the skin. Recent strides in the field have identified several histamine-dependent and -independent pruriceptive pathways and receptors that contribute to acute and chronic itch. The work presented in this thesis further investigates the molecular mechanisms involved in the signaling, development, and sensitization of itch in mouse and human. Most pruritogen receptors are Gq-Protein Coupled Receptors (GqPCR), which canonically activate protein kinase C (PKC); however, little is known about whether specific PKC isoforms regulate itch. The first study in this thesis demonstrates that the isoform …

Investigating The Role Of Genomic Variation In Susceptibility To Environmental Chemicals Across Populations, Lindsay Adrian Holden

Dissertations and Theses

No two individuals are identical. This is true at the genetic level and at the phenotypic level. One of the traits that varies between populations is toxicant susceptibility: some individuals are sensitive to the effects of environmental chemical exposure, and others are resistant. This body of work aims to address the impact of genomic copy number variants (CNV)--large (>1 Kb) duplications or deletions across the genome--on the toxicant-susceptibility phenotype.

Herein copy number variants were characterized across three commonly used laboratory strains of zebrafish (Danio rerio) and mRNA expression phenotypes were identified in the same strains. It was found that …

Cannibalism In Blepharisma Americanum : A Genome Comparison, Bethaney Gulla-Devaney

Theses, Dissertations, and Projects

Cannibalism is a process in which an organism consumes a member of its own species. The process is intraspecies while predation is interspecies. Unlike predation, literature on the process of cannibalism is largely understudied, particularly in the microbial world. This study focuses on Blepharisma americanum, a species of eukaryotic microbe. In this species, cannibalism can be confirmed visually by a giant cannibal cell digesting victim cells within the food vacuoles. Cannibalism is regularly practiced in B. americanum and I attempt to elucidate the genetic differences between life states: cannibal and vegetative cells. I investigate using bioinformatic approaches: whole transcriptome amplification, …

Animal Agriculture And American Health: The Search For Sustainable Protein, Britta Brinkmann

Biology: Student Scholarship & Creative Works

This study examines the impact large-scale animal agriculture has on the environment. It links the environment and health. The goal is to find protein sources that are sustainable and nutritious in order to replace typical meat and dairy products. A study is proposed to measure the impact of the typical American diet, a vegan diet, an insect-supplemented diet and a diet heavy in seafood.

Comparison Of Soil Development Rate In Reclaimed And Un-Reclaimed Grassland Soil, Abdullah Allahyani

Electronic Theses & Dissertations

Soil formation is a process that entails the breakdown of rock particles otherwise known as weathering. It is a process that is determined by various factors such as time, climate, parent materials, topography, and biota. The exposure of the rock particles to these factors affects the process of soil formation in that more exposure accelerates soil development. To establish the rate of soil development, we based our research on reclaimed and un-reclaimed regions. According to the results, soil developed at a rate of 10-24 cm per annual while on the un-reclaimed land it was 0.05-0.06 cm per annual. The difference …

Rodent Responses To Drought In The Southwestern United States: Resource Utilization Strategies And Effects To Keystone Resources, Charles L. Hayes Iv

Biology ETDs

The role of abiotic and biotic factors in regulating community and population dynamics is a central question of ecological inquiry. In the southwestern United States, the North American monsoon supplies vital pulses of moisture to Sonoran desert, arid grassland, and montane communities. I evaluated abiotic limitation in prairie and montane populations of Gunnison’s prairie dog (Cynomys gunnisoni) using stable isotope analysis to quantify foraging niche widths. Niche widths declined under periods of drought stress. Prairie dogs in montane habitats exhibited seasonal shifts in dietary niche width during favorable growth periods for more nutritious plants using the C_{3 …}

Schistosomiasis In The Wild: A Transcriptomics Perspective On Field-Derived Biomphalaria Pfeifferi And Schistosoma Mansoni, And Their Interactions, Sarah K. Buddenborg

Biology ETDs

Schistosomiasis, caused by trematodes in the genus Schistosoma, is a widespread neglected tropical disease with the species S. mansoni infecting over 100 million people. We aimed to better understand the snail host and parasite responses during intramolluscan stages of infection by performing dual RNA-Seq on field-collected snails with natural infections from western Kenya. We collected uninfected Biomphalaria pfeifferi, B. pfeifferi with a patent cercariae-producing S. mansoni infection, and B. pfeifferi exposed to field-collected S. mansoni at 1 and 3d (days post infection).

We first created a high-quality B. pfeifferi transcriptome to identify the snail response to S. mansoni infection. …

Do We Own Our Bodies: The Legality Of Body Ownership, Nicole Marie Kasman

Biology: Student Scholarship & Creative Works

In common times, property ownership has become a hard pressed issue as people try and claim what is rightfully theirs. As medical practices have expanded, the problem of ownership has also extended to the human body and thus questions of ownership arise. It is a common belief that each individual owns their own body but this will be shown to be untrue throughout this paper. Not only that but this paper will also show potential benefits of following through with the body belonging to the common biomass rather than each individual. Court cases such as Moore vs Reagents of the …

Using Computational Bayesian Statistics To Analyze Parameters In A Differential Equation Model, Jacob Menix

Mahurin Honors College Capstone Experience/Thesis Projects

The purpose of this project is to use Bayesian statistics to analyze values of parameters for a previously developed system of differential equations which describes the healing process of diabetic foot ulcers. The model describes the relationships between matrix metalloproteinases (MMPs), their inhibitors (TIMPs), and extracellular matrix (ECM). A Bayesian approach is used when the availability of data is sparse, as it is in this case. Delayed Rejection Adaptive Metropolis (DRAM), a MATLAB implementation of a Metropolis-Hastings algorithm, is used to estimate parameters. This approach with the individual patient data allows us to estimate and compare parameters and their pairwise …

Caspase-3 Suppresses Diethylnitrosamine-Induced Hepatocyte Death, Compensatory Proliferation And Hepatocarcinogenesis Through Inhibiting P38 Activation, Na Shang, Thomas Bank, Xianzhong Ding, Peter W. Breslin, Jun Li, Baomin Shi, Wei Qiu

Biology: Faculty Publications and Other Works

It is critical to understand the molecular mechanisms of hepatocarcinogenesis in order to prevent or treat hepatocellular carcinoma (HCC). The development of HCC is commonly associated with hepatocyte death and compensatory proliferation. However, the role of Caspase-3, a key apoptotic executor, in hepatocarcinogenesis is unknown. In this study, we used Caspase-3-deficient mice to examine the role of Caspase-3 in hepatocarcinogenesis in a chemical (diethylnitrosamine, DEN)-induced HCC model. We found that Caspase-3 deficiency significantly increased DEN-induced HCC. Unexpectedly, Caspase-3 deficiency increased apoptosis induced by DEN and the subsequent compensatory proliferation. Intriguingly, we discovered that Caspase-3 deficiency increased the activation of …

Linking Climate Change And Mortality In Piñon-Juniper Woodlands, From Leaf To Ecosystem, Amanda I. Liebrecht

Biology ETDs

As global climate changes, the Southwestern US is predicted to experience more frequent and intense drought events. Extreme droughts can drive decreases in both physiological and ecosystem function, and can result in widespread tree mortality. Piñon-juniper (PJ) woodlands are a prevalent ecosystem in the region, co-dominated by two tree species, piñon (Pinus edulis) and juniper (Juniperus monosperma). Drought-induced piñon mortality has occurred over the past few decades, coinciding with outbreaks of a piñon-specific bark beetle. Piñon and juniper have different hydraulic strategies (isohydry and anisohydry, respectively) that should affect the way each species responds to drought. …

Understanding Patterns Of Diversity And Evolution In Mainland Anolis Lizards, Levi Nathaniel Gray

Biology ETDs

Patterns of organismal diversity and evolution are often difficult to interpret with a high level of confidence. The number of mechanisms and processes that contribute to shaping patterns of diversity is extensive and is reflected in the many methods researchers have used to infer causation. Taxonomic groups that are well-studied can offer more precise interpretation of pattern and process due to the considerable amount of research addressing ecology, natural history, and behavior of the organisms.

In this dissertation, I explore patterns of phylogenetic and phenotypic variation in Anolis lizards (anoles) by testing hypotheses that could have led to the observed …

Antibiotic Resistance Of Bacteria Isolated From Soils, Jessica Vaughan

Mahurin Honors College Capstone Experience/Thesis Projects

After the discovery of antibiotics, antibiotics have been increasingly implemented into human and veterinary medicine. In addition, antibiotics are inserted into animal feed for non-therapeutic purposes, which potentially leads to the development of antibiotic-resistant pathogens. When the livestock excrete waste onto the soil, the antibiotic resistant bacteria are introduced to the environment. With soil collected from different farms throughout the Bowling Green area, the microbial communities were analyzed to determine its bacterial compositions and their resistances to common antibiotics through a modified agar dilution technique. Once resistant colonies were isolated, they underwent more testing to determine if the colonies could …

An Integrative Approach To Evaluating Radiocesium Contamination In Fukushima Prefecture, James Thornhill

Master of Science in Integrative Biology Theses

An earthquake in Japan led to the meltdown of the Fukushima Daiichi Nuclear Power Plant which released radionuclides into the surrounding regions. Of these radionuclides, cesium-137 (¹³⁷Cs⁺) has been shown to be the most abundant. Research has shown that adsorption of K⁺ and Cs⁺ on 2:1 clay minerals can collapse the interlayers, causing the adsorbed ion to become non-exchangeable. This thesis takes an integrative approach to the restoration of radiocesium-contaminated soil in three parts by 1) evaluating the adsorption behavior and mechanisms of Cs⁺ in vermiculite, 2) using plants as bioindicators to elucidate …

Metastatic Colon Adenocarcinoma Has A Significantly Elevated Expression Of Il-10 Compared With Primary Colon Adenocarcinoma Tumors, Michelle H. Townsend, Abigail M. Felsted, Stephen R. Piccolo, Richard A. Robison, Kim Oneill

Faculty Publications

Classical anti-inflammatory cytokines are known to play a role in both cancer progression as well as cancer elimination. We evaluated the anti-inflammatory cytokines IL-10 and TGF-β in patients with colon adenocarcinoma and metastatic colon adenocarcinoma using immunohistochemical assays to determine the expression of the cytokines between various malignant tissues. We found tissues stained with TGF-β showed no significant upregulation within malignant tumors when compared with normal tissue controls. We observed high levels of TGF-β presence in most tissues similar to GAPDH expression. Within both colon adenocarcinoma and metastatic carcinomas there was a significant variability among patients in the expression of …

Mating Frequencies And Ecological Modeling Of Harvester Ant: Pogonomyrmex Comanche, Rachel Romo

Biology Theses

There is little known about the life history of the imperiled harvester ant Pogonomyrmex comanche. Due to the conservation status, there is a need to learn and understand how these ants are dispersing their genetics within the region. This study focused on resolving uncertainties about genetic diversity, mating frequencies, and habitat associations influencing distribution of this species. It’s well known and studied that queens of different species within this genus take part in multiple mating; but to determine if P. comanchefollows the other species, microsatellite markers were used to conduct paternal analysis on the colonies collected from Camp Swift …

Importance Of Amphibians: A Synthesis Of Their Environmental Functions, Benefits To Humans, And Need For Conservation, Josh West

Honors Program Theses and Projects

Amphibians are among the most threatened species in the world and are subjected to a substantial number of studies that have underscored their ecological and anthropocentric importance. Yet a synthesis of those aspects is in need. In this study I conducted a comprehensive literature review to investigate the importance of amphibians, including medical applications such as tissue regeneration, biomimicry of pharmaceutically useful compounds, direct socio-economic benefits, and overall ecosystem values. It is my intention to promote amphibian conservation by detailing various ecosystem services provided by amphibians and their uses to humans. Amphibians have tissue regenerative abilities, such as the ability …

Habitat Associations And Detectability Of Three Unionid Species Along The Upper Sabine River In East Texas, Jared Dickson

Biology Theses

East Texas contains the highest diversity of mussels in the state. Of the 37 species in East Texas, six are listed by the state as threatened and three have been proposed for listing as threatened or endangered under the U.S. Endangered Species Act. Although diverse, mussel populations are declining and few studies exist that establish habitat relationships identifying determinants of mussel distributions in the upper Sabine River. I explored potential habitat preferences of three state listed species using an occupancy modeling approach, including the: Texas Pigtoe, Fusconaia askewi, Sandbank Pocketbook, Lampsilis satura, and Texas Heelsplitter, Potamilus amphicaenus. …