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Investigating The Role Of Bladder Epithelial Stem Cells In Bladder Mucosal Remodeling And Defense Against Infection, Seongmi Kim Russell

Arts & Sciences Graduate Student Theses and Dissertations

Urinary tract infections (UTIs) can be highly recurrent, and the mechanism(s) governing recurrence susceptibility are mostly unknown. Here I demonstrate bladder epithelial (urothelial)-intrinsic trained immunity as part of a differential mucosal remodeling response to an initial UTI. I established urothelial stem cell (USC) lines from isogenic mice with different UTI histories (naïve, chronic, or self-resolving) and discovered 2880 differential genome-accessible regions, indicating differential epigenetic reprogramming dependent on infection history. Differentiation of USC lines in vitro resulted in polarized urothelial cultures that recapitulated distinct remodeling morphologies seen in vivo and exhibited altered gene expression, including genes involved in cell death pathways. …

Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc

Arts & Sciences Graduate Student Theses and Dissertations

Rapid cell proliferation is a hallmark feature of adaptive immune cells lymphocytes. It is essential for the establishment of diverse antigen receptor repertoires and amplification of antigen-specific immune responses. While such proliferation is beneficial for host protection from infections and cancers, it inevitably elevates the risk of oncogenic transformation. In developing and germinal center B lymphocytes, the risk is further increased by endogenous, genomic insults due to antigen receptor rearrangements and somatic mutations, with which expression of the proto-oncogene c-MYC is closely associated. Nonetheless, frequencies of cancers originated from B lymphocytes are relatively low, suggesting that they are protected from …

The Evolving Mammalian 3d Epigenome, Mayank Choudhary Nishikant Choudhary

Arts & Sciences Graduate Student Theses and Dissertations

One of life’s greatest mysteries is how a 6ft long-strand of DNA (our genome) fits inside the nucleus of a cell that’s less than a tenth of the width of a strand of hair. Adding to that, this genome has functioned faithfully with high fidelity over hundreds of millions of years of evolution is simply mind boggling. Moreover, within our genomes, we find millions of copies of strange genetic hitchhikers that were once thought to be purely self-seeking and parasitic. Critical advances in technology, assay development, sequencing, and computation have brought us today at an opportune moment in space and …

Role Of 4r Tau In Astrocyte-Mediated Neuronal Toxicity And The Progression Of Neurodegenerative Disease, Lubov Alexandra Ezerskiy

Arts & Sciences Graduate Student Theses and Dissertations

The microtubule-binding protein tau is associated with neurodegenerative diseases, including Alzheimer’s disease, progressive supranuclear palsy, and a subset of frontotemporal dementias. In these tauopathies, tau becomes hyperphosphorylated and forms intracellular neurofibrillary tau tangles, contributing to synaptic dysfunction, neuronal death, and severe astrogliosis. Tau can be classified as having a 3-repeat (3R) or 4-repeat (4R) structure, resulting from alternative splicing of exon 10 within the MAPT gene. While the higher deposition of 4R tau characterizes many primary tauopathies, the role of 4R tau in neurodegenerative disease pathogenesis remains unclear. To investigate the role of tau isoforms in disease, we created tau …

C. Elegans Response To Cadmium Toxicity, Brian James Earley

Arts & Sciences Graduate Student Theses and Dissertations

Cadmium is an environmental pollutant and significant health hazard that is similar to the physiological metal zinc. Residing in the same group of the periodic table, cadmium and zinc share chemical characteristics that are important for their industrial uses in electroplating, batteries, pigments, and metal alloys. The similarities of ionic cadmium and zinc have significant repercussions on biological systems. While it has long been clear that cadmium is toxic to biological systems, the mechanisms of cadmium toxicity remain poorly understood. In contrast, mechanisms of zinc homeostasis have been elucidated in growing detail. In C. elegans high zinc homeostasis is regulated …

Testing Janzen’S Physiological Barrier Hypothesis Through Experimental Evolution And Biogeographic Studies On Sister Species Pairs, Vincent John Fasanello

Arts & Sciences Graduate Student Theses and Dissertations

Background: Janzen’s physiological barrier hypothesis suggests that variation in the effectiveness of physiological barriers to dispersal underlies global patterns of speciation and biodiversity. He noted that because a species’ physiology often evolves to match the range of conditions it has experienced in evolutionary history, it is likely that lineages that occupy habitats with wider ranges of temperature variation will tend to be better at dispersing across thermal gradients and will therefore be less likely to speciate as a result of mountain barriers. Despite decades of research into different aspects of this fundamental hypothesis, its assumptions and predictions remain largely untested.Methods: …

The Regulation Of Plasmodium Falciparum Metabolism By Haloacid Dehalogenase Proteins, Philip Frasse

Arts & Sciences Graduate Student Theses and Dissertations

Malaria is an enormous financial and public health burden for much of the world, infecting over 200 million and killing over 400,000 people every year. While much progress has been made combating malaria in the past few decades, those advances have slowed in recent years, partially due to the emergence of resistance to all known antimalarials used to date. To achieve the goal of eliminating malaria as a major global health problem, new therapeutics need to be developed, targeting novel categories of parasite biology. One poorly understood area of parasite biology is the regulation of various metabolic pathways. We have …

The Evolutionary History Of Camelina Crantz (Brassicaceae) And Domestication Of The Biofuel Crop, C. Sativa (L.) Crantz, Jordan Brock

Arts & Sciences Graduate Student Theses and Dissertations

The mustard family, Brassicaceae, is a large and economically important group of plants comprising ~350 genera and ~4060 species. Within the family, one genus, Camelina, has been neglected and nearly forgotten until recent decades. This genus comprises between 7 – 9 species, and includes Camelina sativa, an ancient oilseed crop cultivated for thousands of years in Europe. An allohexaploid, C. sativa contains high levels of omega-3 fatty acids and a seed oil composition amenable for production of aviation jet fuel. With a short generation time and ability to be cultivated on marginal soils with few inputs, C. sativa is set …

Phenotyping And Preclinical Meta-Analysis Of Behavioral Outcomes From Complete Freund’S Adjuvant-Induced Inflammatory Pain In The Rodent Hind-Paw, Dominika J. Burek

Arts & Sciences Graduate Student Theses and Dissertations

Pain and opioid use disorder prevalence, diagnoses of mental health disorders, and rate of suicide have all skyrocketed over the last 30 years as a matrix of public health crises. Each reduces quality of life and installs risk of the others; together, they have burdened our country with nearly unmanageable healthcare challenges. Although the critical demand for novel and more effective therapeutics has been clear for decades, relatively little progress has been made to address pain and its comorbidities. Repeated clinical trial failures have called into question the preclinical evidence upon which they are based. Preclinical models of pain-induced negative …

Dendritic Processing And Efficient Coding In The Retina, Jen-Chun Hsiang

Arts & Sciences Graduate Student Theses and Dissertations

In early sensory systems, a copious amount of information needs to be simultaneously processed to extract salient stimulus features and compress representations for efficient transmission. My thesis addresses how the retina processes visual information to detect specific motion patterns and efficiently encode our environment for perception. Around 40 retinal ganglion cell (RGC) types in mammals send specific feature representations through their axons from the retina to the brain. RGCs are the sole source of visual information to the brain. Recent studies suggest that amacrine cells (ACs) generate feature-selective responses of RGCs, but little is known about their neuronal computations. We …

Copper-Mediated Regulation Of A Traditional Iron Uptake System In Uropathogenic Escherichia Coli., George Lwanga Katumba

Arts & Sciences Graduate Student Theses and Dissertations

Transition metals constitute an important part of the host-pathogen interface. Iron is an essential nutrient that functions as a cofactor for numerous bacterial and host proteins, as either a ligand for oxygen in carrier proteins or an enzyme catalytic site due to its natural redox properties. As part of the innate immune response, infected hosts sequester iron from pathogens to limit their growth, a phenomenon known as nutritional immunity. On the other hand, copper ions are deployed at infection sites as a potent antimicrobial agent to kill bacteria. The ability to survive within multiple, often harsh, microenvironments is fundamental to …

Metabolic Control And Immune Barriers Of Hematopoietic Stem Cells, Hannah Pizzato

Arts & Sciences Graduate Student Theses and Dissertations

Hematopoietic stem cells (HSCs) have the unique ability to self-renew for life, to differentiate into mature blood lineages, and to readily engraft upon intravenous transplantation. As such, they are the only types of stem cells in routine clinical use. Understanding HSCs and hematopoietic development can provide many lessons for other types of stem cells as they near clinical utility. Through bone marrow transplantation, it was discovered that cells exist with regenerative potential. This led to the search to purify these cells and to determine the function of other hematopoietic cells. By isolating and transplanting cells expressing different combinations of surface …

Regulation Of Host-Microbe Interactions In Autoimmunity And Antiviral Immunity By Cytosolic Nucleic Acid Sensing And Interferon Signaling, Derek Jerome Platt

Arts & Sciences Graduate Student Theses and Dissertations

Cytosolic nucleic acid sensing and interferon (IFN) signaling are central to the host immune response to microbial pathogens. However, dysregulation of immunological pathways such as these can result in devastating autoimmune disease. In order to provide a robust immune response to pathogen without causing harm to self, the host immune system must engage in a delicate balancing act, interacting with microbes and determining whether they are commensal or pathogenic. The cGAS-STING pathway is a key regulator of host-microbe interactions by cytosolic nucleic sensing and IFN signaling. Loss of function in the cGAS-STING pathway leads to increased susceptibility to pathogenic threats, …

Exploring The Intrinsic And Extrinsic Factors That Regulate Breast Cancer Cell Dormancy, Qihao Ren

Arts & Sciences Graduate Student Theses and Dissertations

Breast cancer can recur in patients months to decades after initial diagnosis and treatment. There is mounting evidence that dormant breast disseminated tumor cells (DTCs) exist in distant organs, whose reactivation results in cancer recurrence. However, the mechanisms that control tumor cell dormancy remain poorly understood, making it difficult to predict which patients will recur and develop cancer recurrence. Unfortunately, the extreme rarity of dormant DTCs has been the major obstacle to their study. To overcome this challenge, we developed an efficient system to isolate and study rare dormant tumor cells from metastatic organs. Using this system and single cell …

Functional Optical Imaging Of The Developing Mouse Cortex In Health And Disease, Rachel Marlene Rahn

Arts & Sciences Graduate Student Theses and Dissertations

Neurodevelopmental disorders (NDDs) are a heterogeneous family of disorders characterized by the presence of abnormal developmental trajectories. Functional connectivity (FC) neuroimaging provides a minimally-invasive method by which to investigate the progression of these disorders and identify potential biomarkers of disease-related dysfunction for use in therapeutics’ development. My thesis work therefore took several approaches to the question of how the functional connectome reflects developmental change as well as system-wide perturbations from environmental or genetic factors. I explored the use of optical fluorescence and intrinsic signal imaging to characterize FC and stimulation-derived responses in a NDD model of perinatal exposure to selective …

Peripheral Nerve Macrophages And Their Implications In Neuroimmunity, Peter Leon Wang

Arts & Sciences Graduate Student Theses and Dissertations

Macrophages are innate immune cells that protect against pathogens and maintain tissue integrity. In vertebrates, macrophages reside in every tissue where they perform specific functions from early development through adulthood. While macrophages provide important functions across all tissues, a major focus in recent years has been the role of resident brain macrophages, known as microglia, in neurodegeneration. As microglia have been shown to affect brain development, homeostasis, and disease, they demonstrate how immune cells critically mediate neurological health and point to the broader significance of neuroimmune interactions, or the coordinated actions of the nervous and immune systems for maintaining tissue …

Comparative Analysis Of Longevity And Stress Resiliency Benefits Of Supplementation With High-Antioxidative Capacity Juices In Organisms That Are Representative Of Humans, Meghan Long

Honors Scholar Theses

Neurodegenerative disease presents itself in a complex array of illnesses that is increasingly affecting the geriatric population. There has not been research on a common cause since there are a culmination of reasons that are probable ranging from genetic to environmental factors. Antioxidants have been known to prevent and protect against the damage that is otherwise caused by reactive oxygen species (ROS). Thus, high-capacity antioxidant juices supplemented into the diet of animal models such as Caenorhabditis elegans, Drosophila melanogaster, rats, and humans will allow for the study of the possible benefits.

Although a conclusion and common causation on the usage …

Pancreatic Cancer: Novel Therapy, Research Tools, And Educational Outreach, Ayrianne J. Crawford

Theses & Dissertations

Since the 1980’s, legislatures have invested immense effort into strategies to capitalize on the United States’ global lead in basic and translational research. This is largely motivated by the discrepancy the US faces in converting its world leading research discoveries and innovations into commercial products, relative to other countries. This truncated productivity leaves the US out of substantial GDP growth and reduces public access to new innovations. Proponents of government and university owned patents reason that enhanced public private partnerships narrow the gap between the technology transfer of basic research discoveries and accessible commercial products.

With these concepts of technology …

Examination Of Methylation Status And Occupancy Of Dna Methylation Modifying Proteins On Regulatory Regions Of The Dax-1 Gene, Caroline P. Riedstra

Master's Theses

Epigenetic modifications influence gene expression and thereby play a pivotal role in development and disease. Misregulation and mutations in the DAX-1 gene, or Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X chromosome, gene 1, have been implicated in Adrenal Hypoplasia Congenita (AHC) and Dosage Sensitive Sex Reversal (DSS). The orphan nuclear hormone receptor DAX-1 is expressed predominantly in tissues such as the testes, ovaries, breast, adrenal cortex, and lung. Critically, DAX-1 may serve as an indicator of aberrant growth in these tissues. Here we hypothesize that DAX-1 is epigenetically regulated, specifically in cancer cells, thereby reducing its …

Understanding The Metabolic Regulation Of Trained Immunity By Palmitic Acid, Khaleda Aqaei, Brooke A. Napier

McNair Symposium

Sepsis is an inflammatory disease that occurs when the body’s response to an infection becomes dysregulated, and infection-fighting processes of the body damage tissues via inflammation, resulting in organ failure and death. Currently, the role for diet in regulating sepsis susceptibility and severity is not fully understood. The Western Diet (WD), the most prevalent diet worldwide, is high in saturated fatty acids (SFAs) and sucrose, and low in fiber. Previously, we have used a lipopolysaccharide (LPS)-induced sepsis mouse model to show that mice fed a Western Diet (WD) or a diet enriched only in SFAs (Ketogenic Diet; KD), experience increased …

The Effect Of Apremilast On Circadian Rhythm In The Ventral Tegmental Area, Courtney Ledford, Angela Ozburn

McNair Symposium

Chronic binge drinking negatively impacts society and is a leading cause of preventable deaths. The purpose of the experiment is to determine if regulation of circadian rhythms in the ventral tegmental area (VTA) will contribute to less ethanol consumption. The VTA plays a major role in addiction. A simple genetic animal model examines iHDID-1 mice and their binge-like drinking intake. The mice undergo Drinking in the Dark (DID) for 6 weeks prior to administration of apremilast or saline treatment at weeks 7 and 8. The mice are exposed to DID and sacrificed at two separate time points (ZT 3 and …

Efficacy Of Curcumin In Asthma: A Systematic Review And Meta Analysis, Tabitha Grow, Adam Sadowski

McNair Symposium

Over 23 million people are affected by asthma in the United States and 262 million individuals globally. Asthma, if poorly controlled, is associated with significant morbidity as well as increased risk for mortality. Asthma involves several complex inflammatory pathways and processes including an increase in immune cell activation. Curcumin, the active constituent found in turmeric, has been studied in numerous in-vivo and in-vitro studies to generate anti-inflammatory effects in pulmonary diseases and, more recently, an increase in clinical data has become available. Since the most recent review assessing the role of curcumin in pulmonary disorders, additional clinical trials have been …

A New Function For Amyloid-Like Interactions: Cross-Beta Aggregates Of Adhesins Form Cell-To-Cell Bonds, Peter N. Lipke, Marion Mathelié-Guinlet, Albertus Viljoen, Yves F. Dufrêne

Publications and Research

Amyloid structures assemble through a repeating type of bonding called “cross-β”, in which identical sequences in many protein molecules form β-sheets that interdigitate through side chain interactions. We review the structural characteristics of such bonds. Single cell force microscopy (SCFM) shows that yeast expressing Als5 adhesin from Candida albicans demonstrate the empirical characteristics of cross-β interactions. These properties include affinity for amyloid-binding dyes, birefringence, critical concentration dependence, repeating structure, and inhibition by anti-amyloid agents. We present a model for how cross-β bonds form in trans between two adhering cells. These characteristics also apply to other fungal adhesins, so the mechanism …

Scaling Up Sagebrush Chemistry With Near-Infrared Spectroscopy And Uas-Acquired Hyperspectral Imagery, Peter J. Olsoy, Brecken C. Robb, Jennifer Sorenson Forbey, T. Trevor Caughlin, Chelsea Merriman, Jordan D. Nobler

Biology Faculty Publications and Presentations

Sagebrush ecosystems (Artemisia spp.) face many threats including large wildfires and conversion to invasive annuals, and thus are the focus of intense restoration efforts across the western United States. Specific attention has been given to restoration of sagebrush systems for threatened herbivores, such as Greater Sage-Grouse (Centrocercus urophasianus) and pygmy rabbits (Brachylagus idahoensis), reliant on sagebrush as forage. Despite this, plant chemistry (e.g., crude protein, monoterpenes and phenolics) is rarely considered during reseeding efforts or when deciding which areas to conserve. Near-infrared spectroscopy (NIRS) has proven effective in predicting plant chemistry under laboratory conditions in …

Pgc1Α Is Required For The Renoprotective Effect Of Lncrna Tug1 In Vivo And Links Tug1 With Urea Cycle Metabolites, Li Li, Jianyin Long, Koki Mise, Daniel L Galvan, Paul A Overbeek, Lin Tan, Shwetha V Kumar, Wai Kin Chan, Phillip L Lorenzi, Benny H Chang, Farhad R Danesh

Faculty, Staff and Students Publications

lncRNA taurine-upregulated gene 1 (Tug1) is a promising therapeutic target in the progression of diabetic nephropathy (DN), but the molecular basis of its protection remains poorly understood. Here, we generate a triple-mutant diabetic mouse model coupled with metabolomic profiling data to interrogate whether Tug1 interaction with peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) is required for mitochondrial remodeling and progression of DN in vivo. We find that, compared with diabetic conditional deletion of Pgc1α in podocytes alone (db/db; Pgc1αPod-f/f), diabetic Pgc1α knockout combined with podocyte-specific Tug1 overexpression (db/db; TugPodTg; Pgc1αPod-f/f) reverses the protective phenotype of …

Do Early-Successional Weeds Facilitate Or Compete With Seedlings In Forest Restoration? Disentangling Abiotic Versus Biotic Factors, Mylen Arias, Rupesh R. Kariyat, Kimberly Wahl-Villarreal, Stephany Mendez, Jesus Chavana, Bradley O. Christoffersen

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Biology)

1. Semi-arid forests need cost-effective restoration strategies to address their severe degradation. Tree shelters are often used to minimize abiotic and biotic stress during seedling establishment. We asked if early-successional weeds act as a natural shelter by facilitating native seedlings, contingent on abiotic and biotic stressors and seedling ecological strategy.

2. We conducted a manipulative weed exclusion experiment at a semi-arid site in South Texas targeted for large-scale forest restoration to discern the net effect of weeds on the growth and survival of target thornscrub tree and shrub seedlings. We assessed the roles of contrasting seedling ecological strategies (fast vs. slow growth …

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Assessing The Short-Term Effects Of Translocation On Freshwater Mussels: Is Habitat Or Water Quality More Important?, Joshua D. Arnold

Masters Theses

Freshwater mussels (Order: Unionida) are very important to the function of aquatic ecosystems and are typically indicators of good water quality. They provide a valuable link between the water column and the benthic substrate in which they live and are a valuable food resource for many species of animals. However, most species native to North America are currently threatened with extinction, to the point that more than 70% of native freshwater mussels are listed as either threatened or endangered at the state or federal level. The cause of this decline can be attributed to historical over exploitation, habitat alteration, and …

Trem2 Is Thyroid Hormone Regulated Making The Trem2 Pathway Druggable With Ligands For Thyroid Hormone Receptor., Skylar J. Ferrara, Priya Chaudhary, Margaret J. Debell, Gail Marracci, Hannah Miller, Evan Calkins, Edvinas Pocius, Brooke A. Napier, Ben Emery, Dennis Bourdette, Thomas S. Scanlan

Biology Faculty Publications and Presentations

Triggering receptor expressed on myeloid cells-2 (TREM2) is a cell surface receptor on macrophages and microglia that senses and responds to disease-associated signals to regulate the phenotype of these innate immune cells. The TREM2 signaling pathway has been implicated in a variety of diseases ranging from neurodegeneration in the central nervous system to metabolic disease in the periphery. Here, we report that TREM2 is a thyroid hormone-regulated gene and its expression in macrophages and microglia is stimulated by thyroid hormone and synthetic thyroid hormone agonists (thyromimetics). Our findings report the endocrine regulation of TREM2 by thyroid hormone, and provide a …

A Noncoding Rna Modulator Potentiates Phenylalanine Metabolism In Mice, Yajuan Li, Zhi Tan, Yaohua Zhang, Zhao Zhang, Qingsong Hu, Ke Liang, Yao Jun, Youqiong Ye, Yi-Chuan Li, Chunlai Li, Lan Liao, Jianming Xu, Zhen Xing, Yinghong Pan, Sujash S Chatterjee, Tina K Nguyen, Heidi Hsiao, Sergey D Egranov, Nagireddy Putluri, Cristian Coarfa, David H Hawke, Preethi H Gunaratne, Kuang-Lei Tsai, Leng Han, Mien-Chie Hung, George A Calin, Fares Namour, Jean-Louis Guéant, Ania C Muntau, Nenad Blau, V Reid Sutton, Manuel Schiff, François Feillet, Shuxing Zhang, Chunru Lin, Liuqing Yang

Faculty, Staff and Students Publications

The functional role of long noncoding RNAs (lncRNAs) in inherited metabolic disorders, including phenylketonuria (PKU), is unknown. We demonstrated that the mouse lncRNA Pair and human HULC associate with phenylalanine hydroxylase (PAH). Pair-knockout mice exhibited excessive blood phenylalanine, musty odor, hypopigmentation, growth retardation, and progressive neurological symptoms including seizures, which faithfully models human PKU. HULC depletion led to reduced PAH enzymatic activities in human induced pluripotent stem cell (hiPSC)-differentiated hepatocytes. Mechanistically, HULC modulated the enzymatic activities of PAH by facilitating PAH-substrate and PAH-cofactor interactions. To develop a therapeutic strategy for restoring liver lncRNAs, we designed GalNAc-tagged lncRNA mimics that …

Temperatures Influence Susceptibility To Insecticides In Aedes Aegypti And Aedes Albopictus (Diptera: Culicidae) Mosquitoes, Wendy S. Salinas, Teresa Patricia Feria-Arroyo, Christopher Vitek

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Biology)

Aedes aegypti and Aedes albopictus (Diptera: Culicidae) are vectors for several arboviruses, including dengue, Zika virus and chikungunya virus. The primary method of controlling these diseases is controlling the vector population, often with insecticides. Insecticide resistance may impact the success of these efforts. We tested the effect of variable temperature exposures on susceptibility to insecticides by exposing adult A. aegypti and A. albopictus to different temperatures and tested their susceptibility to insecticides. We hypothesized that adults maintained at high temperatures would show increased susceptibility to insecticides relative to lower temperatures. Colony mosquitoes were hatched, reared to adulthood and then maintained …