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Articles 31 - 60 of 1124
Full-Text Articles in Biology
New Paradigms In E. Coli Hemolysin Function And Pathogenesis, Hunter Winston Kuhn
New Paradigms In E. Coli Hemolysin Function And Pathogenesis, Hunter Winston Kuhn
Arts & Sciences Graduate Student Theses and Dissertations
Bacterial pore-forming toxins are potent secreted protein effectors that disrupt cellular ion homeostasis by integrating into the plasma membrane. Among them, the RTX toxin alphahemolysin (HlyA) from uropathogenic Escherichia coli (UPEC) has been extensively studied for its hemolytic activity, broad cell tropism, and role in virulence. HlyA was identified as the first type 1 secreted substrate, with β2 integrin CD18/LFA-1 proposed as its receptor. However, its diverse mechanisms of cellular toxicity and impact on outcomes of urinary tract infection (UTI) have remained incompletely defined. During pyelonephritis, renal epithelial cells are at the front line of infection, directly contacting ascending UPEC …
Investigating Molecular Mechanisms Of Meiosis And Mitosis In Cryptosporidium Parvum, Abigail Kimball
Investigating Molecular Mechanisms Of Meiosis And Mitosis In Cryptosporidium Parvum, Abigail Kimball
Arts & Sciences Graduate Student Theses and Dissertations
The apicomplexan parasite Cryptosporidium parvum (Cp) is a major global contributor to infectious diarrhea in children and poses a serious threat to immunocompromised adults. This dissertation investigates Cp's unique life cycle, which alternates between sexual and asexual reproduction to achieve three critical objectives: producing oocysts capable of transmission, enhancing genetic variation through recombination, and generating sufficient progeny for survival. Sexual reproduction is essential for forming infectious oocysts that facilitate disease transmission. Yet, the process of meiosis in Cp has been historically understudied due to limitations of traditional in vitro culture methods. The newly developed air-liquid interface (ALI) culture system supports …
Cortical Functional Organization In Early Childhood, Jiaxin Tu
Cortical Functional Organization In Early Childhood, Jiaxin Tu
Arts & Sciences Graduate Student Theses and Dissertations
The advent of connectivity-based methods, particularly those utilizing spontaneous BOLD signals, has significantly advanced brain mapping and deepened our understanding of the human brain's functional architecture. While prior research has explored functional organization in early childhood, most studies have focused on coarse, group-level distinctions aligned with adult literature, often within narrow age ranges. This dissertation extends these investigations by examining cortical functional organization in greater detail among healthy infants and toddlers aged 1 to 5 years. Chapter 1 employs spontaneous BOLD signals in sleeping infants and toddlers to derive a group-level functional organization at the resolution of areas and networks. …
Chaperone-Usher Pathway Pili Adhesin Conformations And Inhibitors In Urinary Tract Infections, Edward Lopatto
Chaperone-Usher Pathway Pili Adhesin Conformations And Inhibitors In Urinary Tract Infections, Edward Lopatto
Arts & Sciences Graduate Student Theses and Dissertations
Antibiotic resistant bacteria are becoming increasingly difficult-to-treat resulting in increased morbidity and mortality, especially for common infections such as urinary tract infections (UTIs). Globally, UTIs afflict over 400 million people a year. Numerous different gram-negative and gram-positive bacterial species cause UTIs, including uropathogenic Escherichia coli (UPEC), Klebsiella pneumoniae, and Acinetobacter baumannii. Many of these bacterial species are listed as pathogens of urgent concern by the Center for Disease Control due to the dangerous rise and prevalence of antibiotic resistance necessitating development of new therapeutic measures. Bacteria utilize adhesin factors, such as chaperone-usher pathway (CUP) pili to gain a foothold in …
Robust Embeddings Of Genetics, Anatomy, And State Decoded From A Neuron’S Activity, Aidan Schneider
Robust Embeddings Of Genetics, Anatomy, And State Decoded From A Neuron’S Activity, Aidan Schneider
Arts & Sciences Graduate Student Theses and Dissertations
Neural spike trains are shaped by both extrinsic inputs and intrinsic structural constraints. While prior work has focused on how spike timing encodes externally driven variables, such as stimuli or behavior, this dissertation explores whether principles that organize neural activity in space and time—such as genetic cell type, anatomical location, and arousal state—are also embedded in the spiking output of individual neurons. I hypothesize that these organizing principles are not quenched as irrelevant variability, but rather multiplexed within the neural code itself. To test this, I attempt to decode these principles from the spike trains of neurons recorded in behaving …
Dna-Damaging Chemotherapy Reshapes The Immune Landscape Of The Heart, Ruijun He
Dna-Damaging Chemotherapy Reshapes The Immune Landscape Of The Heart, Ruijun He
Arts & Sciences Graduate Student Theses and Dissertations
Heart failure and ischemic heart disease represent the most common causes of death among cancer survivors. With the tremendous progress in last few decades that empowered early cancer diagnosis and treatment, the population of cancer survivors has been rapidly growing and by 2040, the number is projected to be 26 million. However, despite extensive studies on chemotherapies, there exists a limited understanding of how exposure to chemotherapy reagents impacts heart function in the long term. Moreover, while the roles of immune landscape in heart diseases have recently been revealed, how chemotherapy reagents influence the cardiac immune cells is poorly understood. …
Understanding Host-Pathogen Interactions Using The Caenorhabditis Elegans – Orsay Virus Experimental Model, Chika Fujii
Understanding Host-Pathogen Interactions Using The Caenorhabditis Elegans – Orsay Virus Experimental Model, Chika Fujii
Arts & Sciences Graduate Student Theses and Dissertations
Over an evolutionary timeline, viruses have evolved ways to exploit biochemical pathways of the host for their propagation, whereas host organisms developed mechanisms to recognize virus infection and cope with them. Consequently, a better understanding of the different host factors involved in virus replication could provide insights into potential biological pathways or molecules for therapeutic targeting. Furthermore, detailed dissection of the mechanisms of virus sensing could reveal fundamentally important aspects of virus sensing that are evolutionarily conserved to mammals and offer insights into potentially underexplored areas of research. The C. elegans experimental model offers a useful platform for studying evolutionarily …
Expanding The Druggable Proteome By Integrating Deep Learning With Molecular Simulations To Predict Cryptic Pockets, Artur Meller
Expanding The Druggable Proteome By Integrating Deep Learning With Molecular Simulations To Predict Cryptic Pockets, Artur Meller
Arts & Sciences Graduate Student Theses and Dissertations
Of the protein structures deposited in the Protein Data Bank, less than half have pockets suitable for the binding of drugs. Even when proteins contain pockets in their ground state structures (e.g., the nucleotide-binding active site in myosin motors), achieving specificity remains a central challenge in drug design as many protein families share common structural motifs. Cryptic pockets are cavities absent in ligand-free experimental structures that form due to protein fluctuations in solution. They provide a means to specifically target proteins currently considered undruggable. While cryptic pockets are alluring drug targets, it remains difficult to predict which proteins will form …
Depalmitoylation Regulates Metabolism And Mitochondrial Function, Sarah Lilly Speck
Depalmitoylation Regulates Metabolism And Mitochondrial Function, Sarah Lilly Speck
Arts & Sciences Graduate Student Theses and Dissertations
Tens of millions of Americans suffer from metabolic disorders, predisposing patients to cardiovascular disease, kidney disease, liver disease, infertility, and cancer. Unfortunately, the etiology of many of these diseases remains a mystery, limiting our ability to identify targets for pharmacologic therapies. Due to the relationship between altered lipid dynamics and metabolic dysfunction, we decided to study the effect of the posttranslational lipid modification, S-palmitoylation, on metabolism. S-palmitoylation is the only known reversible lipid modification for proteins, and this depalmitoylation process is catalyzed by acyl-protein thioesterases including APT1 and APT2. We hypothesized that APT deficiency in various tissues would predispose mammals …
Parapinopsin: A Photoswitchable Inhibitory Gpcr For Two-Photon Optogenetics, Bobbie J. Brown
Parapinopsin: A Photoswitchable Inhibitory Gpcr For Two-Photon Optogenetics, Bobbie J. Brown
Arts & Sciences Graduate Student Theses and Dissertations
The development of optogenetic tools has greatly advanced the capability of researchers to understand the connection between neuronal activity and behavior. Optogenetics makes use of opsins, which are light activated ion-channels, ion pumps, or G-Protein coupled receptor (GPCR-based) proteins used to regulate cellular activity. Coupled with technological advances in genetics and optical physics/microscopy, optogenetics can be used to control specific populations of cells in a time-locked, spatially specific manner. The experiments possible with optogenetics depend largely on the capabilities and limitations of the opsin used; thus, there have been continuous efforts to design and employ new opsins with a variety …
Mechanisms Of Mll-Rearranged Infant Leukemogenesis, Jonny Mendoza-Castrejon
Mechanisms Of Mll-Rearranged Infant Leukemogenesis, Jonny Mendoza-Castrejon
Arts & Sciences Graduate Student Theses and Dissertations
Infant leukemias arise as either B cell acute lymphoblastic leukemia (B-ALL) or acute myeloid leukemia (AML) and are primarily driven by MLL/KMT2A-rearrangements (MLLr). Prior work has shown that MLLr transform fetal/neonatal hematopoietic progenitors more efficiently than adult progenitors. However, the genetics and epidemiology of MLLr leukemias present an important paradox. MLLr arise during late gestation under conditions that would seemingly favor leukemic transformation (i.e., fetal/neonatal progenitors have high proliferation rates and self-renewal). Furthermore, MLLr infant leukemias require very few cooperating mutations for transformation. Yet congenital leukemias are 10-fold less common than infant leukemias and >100-fold less common than childhood leukemias …
Parental Guidance Suggested: Genetic, Epigenetic, And Environmental Factors Shape Allele-Specific Gene Regulation In Metabolic Traits, Celine Louise St. Pierre
Parental Guidance Suggested: Genetic, Epigenetic, And Environmental Factors Shape Allele-Specific Gene Regulation In Metabolic Traits, Celine Louise St. Pierre
Arts & Sciences Graduate Student Theses and Dissertations
Deciphering the “genotype to phenotype” map is a crucial goal of biology. We will not improve our ability to predict phenotypes from DNA sequences until we better incorporate epigenetic and environmental variation into our models of human health and disease. Genes are typically presumed to express both parental alleles equally, but genetic and epigenetic factors can cause one allele to function differently than the other (e.g. expressed or silenced more). These allele-specific imbalances can alter the final composition of a gene’s transcriptional product and ultimately shape phenotypes. Allele-specific effects have widespread impacts on complex traits, but how environmental signals contribute …
Oxycodone Self-Administration Modulates Ventral Pallidal Neuron Activity And Plasticity, Jessica Tooley
Oxycodone Self-Administration Modulates Ventral Pallidal Neuron Activity And Plasticity, Jessica Tooley
Arts & Sciences Graduate Student Theses and Dissertations
Opioid use disorder is an urgent public health crisis in the United States. Over 800,000 Americans have died from opioid-related overdoses since 2000. Nearly 30% of people who misuse opioids begin with prescription oral opioids, such as oxycodone, and continue misusing to avoid the immediate aversive state of withdrawal and the persistent dysphoria associated with protracted abstinence from opioids. The persistency of these dysphoric symptoms increases the risk of relapse even after long periods of abstinence. Treatment for opioid use disorder currently consists of pharmacological opioid treatment to reduce withdrawal symptoms and behavioral counseling. However, these strategies have significant real-world …
Circuit-Specific Vulnerability In A Mouse Model Of Alzheimer's Disease, Samuel Brunwasser
Circuit-Specific Vulnerability In A Mouse Model Of Alzheimer's Disease, Samuel Brunwasser
Arts & Sciences Graduate Student Theses and Dissertations
The relationship between brainwide functional decline and accumulation of pathological protein aggregates in Alzheimer’s disease (AD) is complex and not well understood. A set of highly interconnected cortical regions known as the Default Mode Network (DMN) exhibits selective vulnerability to both functional decline and amyloid beta (Aβ) plaques in early AD. One possibility is that early Aβ accumulation in the DMN drives vulnerability. However, it is unknown whether there is something intrinsic to neuronal projections within the DMN that biases these circuits towards dysfunction. In this dissertation, I describe the development of a multisite in vivo electrophysiology pipeline for chronic …
A Subset Of Senescent Myofibroblasts Orchestrates Immunosuppression In Pancreatic Cancer., Jad Belle
A Subset Of Senescent Myofibroblasts Orchestrates Immunosuppression In Pancreatic Cancer., Jad Belle
Arts & Sciences Graduate Student Theses and Dissertations
Pancreatic Ductal Adenocarcinoma (PDAC) is the most lethal solid malignancy with a 12% 5-year survival rate. Most tumors are detected at metastatic stages that are extremely resistant to therapy. PDAC recalcitrance is driven by a unique tumor microenvironment (TME) comprising dense collagenous fibrosis embedded with an abundance of cancer associated fibroblasts (CAFs) and infiltrating leukocytes. Preclinical studies have indicated that PDAC CAFs can have both pro- and anti-tumorigenic effects. This is likely owed to CAF phenotypic heterogeneity which was recently uncovered by single cell transcriptomics. Three major CAF subpopulations have been identified in mouse and human PDAC thus far: myofibroblastic …
Pan-Cancer Universal Targets For Immunotherapy Resulted From Transposable Elements Activation, Yonghao Liang
Pan-Cancer Universal Targets For Immunotherapy Resulted From Transposable Elements Activation, Yonghao Liang
Arts & Sciences Graduate Student Theses and Dissertations
Transposable elements (TEs) contribute to nearly half of the human genome yet have been overlooked in genomic medicines due to the stereotypic impression as “junk DNA” and technical challenges. However, studies in the last two decades demonstrated that dysregulation of the epigenome in cancer cells resurrects the cis-regulatory functions of TEs, including the promoter activities. The tumor-specific TE activation events along with the resulting tumor-specific RNA and protein molecules, provide a potential “gold mine” for identifying tumor-specific therapeutic targets for cancer treatments, including immunotherapy. Here, I present a series of works to investigate the potential of providing actionable, pan-cancer, and …
Induced Cd8a Identifies Enhanced Human Nk Cell Il-15-Induced Proliferation And Metabolism And Modulates Nk Cell Activation, Celia Cubitt
Induced Cd8a Identifies Enhanced Human Nk Cell Il-15-Induced Proliferation And Metabolism And Modulates Nk Cell Activation, Celia Cubitt
Arts & Sciences Graduate Student Theses and Dissertations
Natural Killer (NK) cells are cytotoxic innate lymphoid cells that play an important role in the surveillance and elimination of virally-infected and malignantly-transformed cells. These primary effector functions are achieved by producing cytokines and chemokines which activate and recruit additional immune effectors, as well as direct cytotoxic killing via perforin and granzymes. NK cell function is tightly regulated by a balance of germ-line encoded activating, inhibitory, co-stimulatory, and cytokine receptors expressed at the cell surface. Through these activating and inhibitory receptors, NK cells recognize and kill targets without prior sensitization through the loss of self-identifying molecules such as major histocompatibility …
Disrupting Nrf2-Driven Cancer Biology Through One-Carbon Metabolism Inhibition, Julius Chembo
Disrupting Nrf2-Driven Cancer Biology Through One-Carbon Metabolism Inhibition, Julius Chembo
Arts & Sciences Graduate Student Theses and Dissertations
Cancer remains a leading cause of mortality worldwide, with treatment resistance and recurrence posing major barriers to long-term survival. Despite advancements in targeted therapies, many cancers develop resistance to chemotherapy, radiation, and immunotherapy, significantly limiting their effectiveness. One key driver of therapeutic resistance is nuclear factor erythroid 2-related factor 2 (NFE2L2/NRF2), a transcription factor that regulates antioxidant responses and drug detoxification. While NRF2 protects normal cells from oxidative stress, its aberrant activation in cancer promotes tumor progression, metabolic reprogramming, and resistance to standard treatments. Alarmingly, NRF2 hyperactivation is implicated in some of the most aggressive and refractory malignancies, yet no …
The Role Of The Cgas-Sting Sensing Pathway In Hiv-1 And Sars-Cov-2 Infections, Jenna Eve Eschbach
The Role Of The Cgas-Sting Sensing Pathway In Hiv-1 And Sars-Cov-2 Infections, Jenna Eve Eschbach
Arts & Sciences Graduate Student Theses and Dissertations
Human immunodeficiency virus type I (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the causative agents of two unique pandemics. For a successful replication cycle to occur, viruses need to strategically outmaneuver host cell defenses. The innate immune system is the first line of defense against viruses and other pathogens. Host pattern recognition receptors detect viral nucleic acids and initiate signaling cascades that culminate in the expression of interferon (IFN) and transcriptional upregulation of antiviral interferon-stimulated genes (ISGs). This dissertation examines the involvement of the innate immune response during early, post-entry steps of HIV-1 and SARS-CoV-2 infection. During …
Functional Diversification Of Rice Ago1 Proteins, Rachel Elie Jouni
Functional Diversification Of Rice Ago1 Proteins, Rachel Elie Jouni
Arts & Sciences Graduate Student Theses and Dissertations
Global demand for food is outpacing gains from conventional plant breeding. Scientists have turned to molecular crop breeding techniques to increase crop output and mitigate global hunger; however, a common setback in this process is the pleiotropic effects of target genes. We need to develop strategies to specifically modulate desired traits without incurring undesired penalties. Natural evolution frequently balances such tradeoffs through extensive regulation, which we can leverage to produce more specific results. Reproductive development is an important target of breeding efforts due to its direct effect on yield. Rice, a major staple food crop for half the world’s population, …
Targeting Nonsense-Mediated Rna Decay In Splicing Factor Mutant Myeloid Malignancies, Claudia Cabrera
Targeting Nonsense-Mediated Rna Decay In Splicing Factor Mutant Myeloid Malignancies, Claudia Cabrera
Arts & Sciences Graduate Student Theses and Dissertations
Approximately 50% of patients with myelodysplastic syndromes (MDS) (which frequently progresses to secondary acute myeloid leukemia [AML]), 60% of chronic myelomonocytic leukemia (CMML) and 20% of de novo AML harbor heterozygous somatic mutations in spliceosome genes. We and others have shown that mutations in spliceosome genes U2AF1, SF3B1, SRSF2 and ZRSR2 cause alterations in RNA splicing, leading to production of numerous aberrant RNAs. Interestingly, spliceosome mutant cells are more sensitive to genetic alterations or drugs that further perturb RNA splicing, compared to wild-type cells. The sensitivity of spliceosome mutant cells to further perturbations in RNA splicing raises the possibility that …
Jarid2-Mediated Reprogramming Of Human Hematopoietic Progenitors For Stem Cell Transplantation, Wentao Han
Jarid2-Mediated Reprogramming Of Human Hematopoietic Progenitors For Stem Cell Transplantation, Wentao Han
Arts & Sciences Graduate Student Theses and Dissertations
Hematopoietic stem cell transplantation (HSCT) is a well-established treatment for various hematological disorders. Umbilical cord blood (UCB) has emerged as an alternative source of hematopoietic stem and progenitor cells (HSPCs). However, the limited number of functional repopulating cells in UCB units has encouraged researchers to develop methods to expand them ex vivo. Hematopoiesis is strictly regulated by epigenetic modifiers. JARID2 is a co-factor of the Polycomb Repressive Complex 2 (PRC2), which recruits the complex to specific genomic loci and promotes the deposition of Histone 3 lysine 27 trimethylation (H3K27me3), a repressive epigenetic mark that mediates condensed chromatin packing to silence …
The Role Of Il-33 In Itch, Anna M. Trier
The Role Of Il-33 In Itch, Anna M. Trier
Arts & Sciences Graduate Student Theses and Dissertations
Chronic itch is associated with a broad range of medical conditions, from inflammatory skin diseases to cancer and organ dysfunction, and has a lifetime prevalence of up to 20%. Despite being common and debilitating, the cellular and molecular mechanisms that drive chronic itch are just beginning to be elucidated. Thus, therapeutic options are limited. Recent studies have identified that various pro-inflammatory cytokines can directly activate sensory neurons. This has resulted in mounting interest in the therapeutic potential of inhibiting these neuro-immune interactions. IL-33 is constitutively expressed by epithelial cells, which allows for its rapid release upon tissue damage or stress. …
Understanding Loss Of Beta-Cell Identity And Progression Of Diabetes In Polygenic Mouse Models Of T2dm, Sumitkumar Patel
Understanding Loss Of Beta-Cell Identity And Progression Of Diabetes In Polygenic Mouse Models Of T2dm, Sumitkumar Patel
Arts & Sciences Graduate Student Theses and Dissertations
Type 2 diabetes (T2DM) is caused by the complex interaction of multiple genes and environmental factors. T2DM is characterized by hyperglycemia, insulin resistance in peripheral tissues and impaired insulin secretion by the pancreas. While the decline in insulin production and secretion was previously attributed to apoptosis of insulin-producing β-cells, recent studies indicate that β cell apoptosis rates are relatively low in diabetes. In this dissertation, I investigated β-cell failure in diabetes using KK and KKAy mouse models of polygenic T2DM, which spontaneously develop hyperglycemia, glucose intolerance, glucosuria, impaired insulin secretion and insulin resistance. I found that β-cell failure in KK …
Effects Of Angptl3 Deficiency On The Regulation Of Hepatic Lipoprotein Production And Lipid Metabolism, Kendall Helene Burks
Effects Of Angptl3 Deficiency On The Regulation Of Hepatic Lipoprotein Production And Lipid Metabolism, Kendall Helene Burks
Arts & Sciences Graduate Student Theses and Dissertations
Cardiovascular disease is the leading cause of death worldwide. A major treatment goal is to lower plasma lipids, especially low-density lipoprotein cholesterol (LDL), the cardinal risk factor for coronary artery disease (CAD). Patients with familial hypercholesterolemia (FH) experience early-onset CAD due to extremely high LDL. Underdiagnosis and undertreatment of FH are exacerbated by limited therapeutic options. However, one strategy has successfully lowered LDL in FH patients: Inhibition of the hepatically secreted protein Angiopoietin-like protein 3 (ANGPTL3). Despite promising clinical data, the mechanism by which ANGPTL3 inhibition lowers LDL has not been fully described. Although ANGPTL3 has been shown to modulate …
Characterizing Piezo1 Mechanotransduction In Articular Chondrocytes, Jaquelin Marlen Garcia Castorena
Characterizing Piezo1 Mechanotransduction In Articular Chondrocytes, Jaquelin Marlen Garcia Castorena
Arts & Sciences Graduate Student Theses and Dissertations
Osteoarthritis (OA) is the most common degenerative joint disease, affecting more than 350 million people worldwide. Along with inflammation and pain, a hallmark of OA is the degradation of articular cartilage (AC), an avascular and aneural tissue that coats and facilitates the bending of diarthrodial joints. AC withstands millions of cyclic mechanical loads annually, and chondrocytes, the only resident cells in the tissue, sense these loads through mechanically gated ion channels, including Transient Receptor Potential Vanilloid 4 (TRPV4), PIEZO1 and PIEZO2. PIEZO1 is a highly expressed calcium ion channel in chondrocytes that can be activated through mechanical loading or chemically …
Single-Cell Analysis Of Clonal And Transcriptional Dynamics During Direct Reprogramming, Brent Biddy
Single-Cell Analysis Of Clonal And Transcriptional Dynamics During Direct Reprogramming, Brent Biddy
Arts & Sciences Graduate Student Theses and Dissertations
Direct lineage reprogramming converts one cell type into another, a process characterized by significant heterogeneity. Single-cell genomic techniques have been instrumental in dissecting this variability, yet they often fail to preserve lineage relationships. Here, I present CellTagging, a sequential, combinatorial indexing method that enables the reconstruction of clonal history and gene expression dynamics at single-cell resolution. This facilitates the construction of multi-level lineage trees, providing insights into cellular reprogramming trajectories. We applied CellTagging to investigate direct lineage reprogramming of mouse embryonic fibroblasts into induced endoderm progenitors. Our analysis revealed two distinct reprogramming trajectories: one leading to successful conversion and another …
Investigating The Roles Of Sox10 And Etv4 In Melanocyte And Melanoma Development, Catherine Marie Newsom-Stewart
Investigating The Roles Of Sox10 And Etv4 In Melanocyte And Melanoma Development, Catherine Marie Newsom-Stewart
Arts & Sciences Graduate Student Theses and Dissertations
The neural crest is a transient, multipotent cell population unique to vertebrates that gives rise to diverse lineages, including craniofacial cartilage, peripheral neurons, glia, and pigment-producing melanocytes. Proper specification and differentiation of neural crest derivatives are orchestrated by tightly regulated gene regulatory networks, and disruption of these developmental programs can lead to congenital disorders and malignancies. Melanocytes, derived from the neural crest, are best known for their role in skin pigmentation but also contribute to homeostasis and specialized functions in the eye, ear, and heart. These cells produce melanin to protect tissues from ultraviolet radiation and oxidative damage, and they …
Mechanisms Of Protective Humoral Immunity And Pathogenesis In Alphavirus Infection, Natasha Monir Kafai
Mechanisms Of Protective Humoral Immunity And Pathogenesis In Alphavirus Infection, Natasha Monir Kafai
Arts & Sciences Graduate Student Theses and Dissertations
Alphaviruses are enveloped, mosquito-transmitted, positive-sense RNA viruses of the Togaviridae family classified into Old and New World groups based on endemic regions and human disease characteristics. Old World alphaviruses, including chikungunya virus preferentially cause arthritogenic disease, whereas New World viruses like Venezuelan equine encephalitis virus (VEEV), Eastern equine encephalitis virus (EEEV), and Western equine encephalitis virus (WEEV) can cause neurological disease. Since the 1920s, VEEV has been responsible for major periodic outbreaks affecting hundreds of thousands of humans and equines in South and Central America. Expansion of mosquito vectors raises concern for possible VEEV reemergence. In addition, VEEV is a …
Proteogenomic Analysis To Inform Causal Gene Prioritization For Human Disease, Daniel Western
Proteogenomic Analysis To Inform Causal Gene Prioritization For Human Disease, Daniel Western
Arts & Sciences Graduate Student Theses and Dissertations
Genome-wide association studies (GWAS) have been key in expanding our understanding of the genetic contributions to common diseases. However, these genetic associations frequently fail to clarify causal disease mechanisms, as they often fall in non-coding regions and are difficult to interpret. One solution is to perform a GWAS for the levels of a cellular trait, known as quantitative trait locus (QTL) mapping. Through methods such as colocalization, Mendelian Randomization, and transcriptome/proteome-wide association studies, the QTL variants can be compared to disease GWAS, identifying shared variation between cellular and disease traits. We can then prioritize cellular traits as potential causative, targetable …