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Full-Text Articles in Biology

Identification Of Bhlhe40 And Irg1 As Essential Regulators Of The Inflammatory Response To Mycobacterium Tuberculosis, Jeremy Peter Huynh Aug 2018

Identification Of Bhlhe40 And Irg1 As Essential Regulators Of The Inflammatory Response To Mycobacterium Tuberculosis, Jeremy Peter Huynh

Arts & Sciences Graduate Student Theses and Dissertations

Protective immune responses to Mycobacterium tuberculosis (Mtb) must induce bactericidal functions while minimizing damage to the lung. Such responses require precise control of pro- and anti-inflammatory factors to regulate the recruitment and function of protective immune cells but the mechanisms by which this control is exerted remain incompletely defined. Basic helix-loop-helix family, member e40 (Bhlhe40) is a transcription factor known to regulate production of pro- and anti-inflammatory cytokines that affect protective immunity to Mtb. Immune-responsive Gene 1 (Irg1) is an enzyme that generates itaconate, a metabolite with potential anti-inflammatory and antibacterial roles during Mtb infection. The impact of Bhlhe40 and …


Methods To Record Transcription Factor Binding And Enhancer Activity Throughout Cellular Differentiation, Zongtai Qi Aug 2018

Methods To Record Transcription Factor Binding And Enhancer Activity Throughout Cellular Differentiation, Zongtai Qi

Arts & Sciences Graduate Student Theses and Dissertations

The ability to create distinct cell types is fundamental for the development of multicellular organisms. Since all cells in an organism contain the same genes, cellular diversity is achieved through the transcriptional network where transcription factors (TFs) interacts with cis-regulatory elements, leading to the selective transcription of different sets of genes. To better understand the functions of TFs and regulatory elements underlying cell fate decisions, we developed methods that are able to record their activities throughout cellular differentiation. In Chapter 2, we developed a degradation domain based induction system for ҃alling CardsӠmethod which maps the binding sites of TFs using …


Smooth As Silk: Translating Discoveries To New Therapies In Amyotrophic Lateral Sclerosis, Wade Self Aug 2018

Smooth As Silk: Translating Discoveries To New Therapies In Amyotrophic Lateral Sclerosis, Wade Self

Arts & Sciences Graduate Student Theses and Dissertations

No effective therapies exist for the treatment of patients suffering from amyotrophic lateral sclerosis, a devastating neurodegenerative disease characterized by motor neuron loss, paralysis, and death on average 3 Р5 years after diagnosis. Although multiple promising candidates have emerged from preclinical experiments in disease models, failure rates of randomized control trials assessing efficacy in humans are over 95%, demonstrating a need to improve the translation of preclinical findings to human biology. In this dissertation, I present original work investigating amyotrophic lateral sclerosis caused by mutations in SOD1 (ALSSOD1) for the successful translation of SOD1-targeting strategies into meaningful treatment options for …


Kdm6b Is Required For Self-Renewal Of Normal And Leukemic Mouse Stem Cells Under Proliferative Stress, Cates Mallaney Aug 2018

Kdm6b Is Required For Self-Renewal Of Normal And Leukemic Mouse Stem Cells Under Proliferative Stress, Cates Mallaney

Arts & Sciences Graduate Student Theses and Dissertations

KDM6B (JMJD3) is one of two known epigenetic modifiers responsible for the removal of the repressive histone mark, histone-3 lysine-27 trimethylation (H3K27me3), and has been shown to play a role in development, differentiation, and inflammatory stress response. Unlike the other H3K27me3 demethylase, UTX (KDM6A), which is frequently mutated in hematopoietic malignancies, KDM6B is upregulated in a myriad of blood disorders. This suggests that it may have important functions in the pathogenesis of hematopoietic cancers. Here, we examined the role of Kdm6b in hematopoietic stem cell (HSC) fate decisions under normal and malignant conditions to evaluate its potential as a therapeutic …


Characterization Of The Celf6 Rna Binding Protein: Effects On Mouse Vocal Behavior And Biochemical Function, Michael A. Rieger Aug 2018

Characterization Of The Celf6 Rna Binding Protein: Effects On Mouse Vocal Behavior And Biochemical Function, Michael A. Rieger

Arts & Sciences Graduate Student Theses and Dissertations

Behavior in higher eukaryotes is a complex process which integrates signals in the environment, the genetic makeup of the organism, and connectivity in the nervous system to produce extremely diverse adaptations to the phenomenon of existence. Unraveling the subcellular components that contribute to behavioral output is important for both understanding how behavior occurs in an unperturbed state, as well as understanding how behavior changes when the underlying systems that generate it are altered. Of the numerous molecular species that make up a cell, the regulation of messenger RNAs (mRNAs), the coding template of all proteins, is of key importance to …


Breath Biomarkers And An Expanded Role For Isoprenoids In Plasmodium Falciparum, Chad Louis Schaber Aug 2018

Breath Biomarkers And An Expanded Role For Isoprenoids In Plasmodium Falciparum, Chad Louis Schaber

Arts & Sciences Graduate Student Theses and Dissertations

Malaria remains one of the deadliest infectious diseases worldwide, and efforts to combat it require novel insights into diagnostics, vector transmission, and drug inhibitor targets. Previous studies suggest that malaria infection causes hosts to preferentially attract the transmission vector, the Anopheles mosquito, but the mechanism and wider implication of these findings were not known. By analyzing the headspace above malaria parasite cultures, we identified several molecules that might engender mosquito attraction. We demonstrated that several of these molecules activate mosquito odorant receptors, including the known plant-emitted mosquito attractant _-pinene. During patient studies involving two independent pediatric clinical populations from Malawi, …


Transcriptional Signatures Of Host Susceptibility In Urinary Tract Infections, Lu Yu Aug 2018

Transcriptional Signatures Of Host Susceptibility In Urinary Tract Infections, Lu Yu

Arts & Sciences Graduate Student Theses and Dissertations

Urinary tract infections (UTI) caused by uropathogenic Escherichia coli (UPEC) are common and highly recurrent. Two important non-behavioral risk factors for UTI in women are genetics and history of two or more episodes of previous UTI. However, specific mechanisms of how these two factors modulate host susceptibility to UTI remain unclear. Concordantly, inbred mice of various genotypes and with different infection histories exhibit different susceptibilities to acute and chronic bladder infection (cystitis), which recapitulates a range of clinical UTI outcomes observed in women. Early host-pathogen interactions have been shown to determine UTI outcomes in mouse models. Here, we used two …


Plant Metabolic Pathways And Regulatory Networks For Aromatic Amino Acids And Hormones, Cynthia Holland Aug 2018

Plant Metabolic Pathways And Regulatory Networks For Aromatic Amino Acids And Hormones, Cynthia Holland

Arts & Sciences Graduate Student Theses and Dissertations

Unlike humans and other metazoans, organisms such as fungi, bacteria, and plants have retained the enzymatic machinery necessary to synthesize their aromatic amino acids de novo. Chorismate, the final product of the shikimate pathway, is the precursor to the three aromatic amino acidsѠtryptophan, tyrosine, and phenylalanineѠand is upstream of a number of plant growth hormones, including auxins and benzoates. Phenylalanine and tyrosine both stem from the precursor prephenate, which is formed from chorismate by chorismate mutase, and use dehydrogenases, aminotransferases, and dehydratases in their biosynthetic pathways. Although aromatic amino acid biosynthesis is important for protein synthesis, secondary metabolism, and human …


Development And Function Of Retinal Ganglion Cell Circuits, Nai-Wen Tien May 2018

Development And Function Of Retinal Ganglion Cell Circuits, Nai-Wen Tien

Arts & Sciences Graduate Student Theses and Dissertations

The function of our nervous system relies on specific patterns of synaptic connections between diverse neuronal cell types. My thesis research addressed how cell-type-specific patterns of connectivity emerge in the developing mouse retina and how they enable mature retinal neurons to detect specific sensory stimuli.Spike trains of the approximately 40 retinal ganglion cell (RGC) types in mammals encode specific features and events in the visual world, and are the sole source of visual information to the brain. Recent studies have begun to dissect the presynaptic circuits underlying diverse RGC light responses, but how cell-type-specific retinal circuits emerge during development is …


Host Determinants Of Protection And Pathogenesis During Chikungunya Virus Infection, Lindsey Elaine Cook May 2018

Host Determinants Of Protection And Pathogenesis During Chikungunya Virus Infection, Lindsey Elaine Cook

Arts & Sciences Graduate Student Theses and Dissertations

Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes acute and chronic polyarthritis. The virus has rapidly emerged over the last decade, and in 2013, CHIKV spread to the Western Hemisphere for the first time, infecting more than 1.8 million people. CHIKV targets the joints and musculoskeletal tissues, resulting in severe myalgia and symmetric polyarthritis that clinically mimics rheumatoid arthritis. Currently, no approved treatment is effective in preventing or controlling CHIKV infection or disease. Pathogenesis of CHIKV is still poorly understood but is thought to reflect an interplay between viral replication and detrimental immune responses. CHIKV patients have increased numbers …


Novel Approaches To Studying The Effects Of Cis-Regulatory Variants In The Central Nervous System, Susan Shen May 2018

Novel Approaches To Studying The Effects Of Cis-Regulatory Variants In The Central Nervous System, Susan Shen

Arts & Sciences Graduate Student Theses and Dissertations

For decades, studies of the genetic basis of disease have focused on rare coding mutations that disrupt protein function, leading to the identification of hundreds of genes underlying Mendelian diseases. However, many complex diseases are non-Mendelian, and less than 2% of the genome is coding. It is now clear that non-coding variants contribute to disease susceptibility, but the precise underlying mechanisms are generally unknown. Cis-regulatory elements (CREs) are transcription factor (TF)-bound genomic regions that regulate gene expression, and variants within CREs can therefore modify gene expression. The putative locations of CREs in a variety of cell types have been identified …


Discovering Rare Hematopoietic Clones Harboring Leukemia-Associated Mutations Using Error-Corrected Sequencing, Andrew Lee Young May 2018

Discovering Rare Hematopoietic Clones Harboring Leukemia-Associated Mutations Using Error-Corrected Sequencing, Andrew Lee Young

Arts & Sciences Graduate Student Theses and Dissertations

Cancer is a heterogeneous group of diseases that currently takes over half a million lives per year in the United States alone. Our understanding of cancer has improved dramatically over the last forty years, beginning with the discovery that cancer is a disease of the genome. Currently, the set of somatic mutations found in malignancy are largely known. The specific somatic mutations driving an individual’s disease can be readily assessed at clinical presentation. Additionally, the functional consequences for many of these mutations are known as well as their role in tumorigenesis. Despite this understanding, a cure for cancer remains elusive.Acute …


Understanding Stroke In The Connected Human Brain, Joshua Sarfaty Siegel May 2018

Understanding Stroke In The Connected Human Brain, Joshua Sarfaty Siegel

Arts & Sciences Graduate Student Theses and Dissertations

Although structural damage from stroke is focal, remote dysfunction can occur in regions of the brain distant from the area of damage. Lesions in both gray and white matter can disrupt the flow of information in areas connected to or by the area of infarct. This is because the brain is not an assortment of specialized parts but an assembly of distributed networks that interact to support cognitive function. Functional connectivity analyses using resting functional magnetic resonance imaging (fMRI) have shown us that the cortex is organized into distributed brain networks. The primary goal of this work is to characterize …


Negative Regulators Of Colonic Peripheral Regulatory T Cell Development, Teresa Lei Ai May 2018

Negative Regulators Of Colonic Peripheral Regulatory T Cell Development, Teresa Lei Ai

Arts & Sciences Graduate Student Theses and Dissertations

Peripheral Treg cells (pTreg cells) maintain immune homeostasis at mucosal interfaces, where they can develop upon activation of naïve CD4+ T cells by bacteria antigen. However, the cellular and molecular requirements that govern their differentiation in inflamed and homeostatic contexts require further elucidation. To circumvent uncertainties in existing methods of distinguishing pTreg cells from thymic Treg cells (tTreg cells), we analyzed monoclonal cell populations of CT2 and CT6 transgenic (Tg) cells that develop into pTreg cells in response to different species of endogenously presented Helicobacter antigen. In our comprehensive assessment of multiple intestinal inflammatory models, including infections and physical injury, …


Correlated Variability And Adaptation In Orbitofrontal Cortex During Economic Choice, Katherine E. Conen May 2018

Correlated Variability And Adaptation In Orbitofrontal Cortex During Economic Choice, Katherine E. Conen

Arts & Sciences Graduate Student Theses and Dissertations

Economic decision-making requires the computation and comparison of subjective values. Several lines of evidence suggest that these processes are mediated by circuits in orbitofrontal cortex (OFC). Neurons in OFC encode the subjective values of choice options and outcomes, and damage to this area leads to selective deficits in value-guided behavior. To understand the nature of choice more thoroughly, it is useful to consider the features of OFC circuits that can limit or enhance information processing. In this document, I present work examining two factors that influence encoding in OFC: noise correlation and value adaptation. In the first study, I show …


Integration Of Local And Regional Regulatory Information In The Human Genome, Hemangi Govind Chaudhari May 2018

Integration Of Local And Regional Regulatory Information In The Human Genome, Hemangi Govind Chaudhari

Arts & Sciences Graduate Student Theses and Dissertations

Gene regulation involves the integration of different sources of information at multiple levels. The action of transcription factors is integrated at cis-regulatory sequences (CRSs). Information from many CRSs is combined to drive spatiotemporally regulated gene expression. Prediction of CRS activity from DNA sequence is challenging because most occurrences of transcription factor binding sites (TFBS) are not functional. I assayed the activity of thousands of genomic sequences with Activator Protein 1 (AP-1) binding sites in K562 cells to identify features in flanking sequences that distinguish functional from non-functional TFBS. I find that sequence features directly adjacent to the AP-1 core motif, …


Discerning Drivers Of Cancer: Computational Approaches To Somatic Exome Sequencing Data, Runjun Kumar May 2018

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 May 2018

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 May 2018

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 May 2018

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 May 2018

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 May 2018

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 May 2018

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 May 2018

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 May 2018

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 May 2018

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 May 2018

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 May 2018

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 May 2018

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 …


Understanding The Paradox Of Genetic Diversity In Uropathogenic E. Coli: The Uncommon Evolution Of A Common Pathogen, Henry Louis Schreiber Dec 2017

Understanding The Paradox Of Genetic Diversity In Uropathogenic E. Coli: The Uncommon Evolution Of A Common Pathogen, Henry Louis Schreiber

Arts & Sciences Graduate Student Theses and Dissertations

Urinary tract infections (UTIs) are the second most common bacterial infection of people in the U.S.A and are frequently recurrent, as an initial UTI is quickly followed by a second episode in 30-35% of cases despite appropriate antibiotic treatment and clearance of the bacteria from the urine. The vast majority, >80%, of UTIs are caused by uropathogenic Escherichia coli (UPEC). UPEC that colonize the bladder are thought to originate in the gut, where they live as commensal organisms. UPEC can be shed in feces to colonize the vagina and/or periurethral area, and then can ascend into the bladder to start …