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2020

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Articles 1651 - 1680 of 1778

Full-Text Articles in Medical Sciences

Investigating The Roles Of The Renal Primary Cilium Through The Use Of Intravital Imaging, Dustin Zachary Revell Jan 2020

Investigating The Roles Of The Renal Primary Cilium Through The Use Of Intravital Imaging, Dustin Zachary Revell

All ETDs from UAB

Primary cilia are small microtubule based appendages present on nearly every cell type in the mammalian body, and are highly conserved from organisms as simple as algae to humans. Cilia function as complex signaling centers integrating a variety of pathways and play critical roles throughout development and in maintaining homeostasis. Mutations to ciliary proteins in humans result in a wide array of diseases termed ciliopathies, which have a broad range of symptoms affecting nearly every organ in the body. Renal primary cilia are present on the apical side of tubular epithelium, where they project into the lumen and are thought …

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Noninvasive Neuromodulation Using A Benchtop Approach To Mri-Guided Focused Ultrasound Blood Brain Barrier Opening, Megan Rich Jan 2020

Noninvasive Neuromodulation Using A Benchtop Approach To Mri-Guided Focused Ultrasound Blood Brain Barrier Opening, Megan Rich

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Fundamental neuroscience research has provided a deeper understanding of the genes, molecules and cellular circuitry involved in neurological disorders, however translating discovery into clinical application remains a major challenge. This bench to bedside gap is in part due to the discrepancy in techniques used in the laboratory vs. the clinic for targeting the mechanisms that underlie disease. Ideally this discrepancy would be resolved not only by implementing novel clinical techniques to provide more precise targeting of disease foci, but also by using the same techniques in the clinic that are used at the lab bench to provide a direct bench …

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Locus Coeruleus Degeneration In Alzheimer’S Disease And Its Effect On Beta-Adrenergic Signaling In The Hippocampus, Bethany Langner Jan 2020

Locus Coeruleus Degeneration In Alzheimer’S Disease And Its Effect On Beta-Adrenergic Signaling In The Hippocampus, Bethany Langner

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Locus coeruleus (LC) degeneration in Alzheimer’s Disease (AD) and loss of noradrenergic (NA) innervation in hippocampus contributes to learning and memory deficits. Recently, a novel rat model (TgF344-AD) has been created that allows for a more thorough investigation into these mechanisms due to its similarity to human AD pathology. The McMahon lab has recently demonstrated heightened long-term potentiation (LTP) and a ‘supersensitivity’ of -adrenergic receptors (-ARs) at excitatory synapses in the dentate gyrus (DG) in TgF344-AD rats. These mechanisms could be responsible for maintaining learning and memory during buildup of AD pathology. The first goal of this Master’s thesis was …

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The Role Of Neutrophils In Chronic Heart Failure, Sergey Antipenko Jan 2020

The Role Of Neutrophils In Chronic Heart Failure, Sergey Antipenko

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Acute myocardial infarction (MI) produces massive, sudden cardiomyocyte death, triggering an inflammatory and healing response that initially leads to scar formation and ultimately may induce progressive ischemic cardiomyopathy and heart failure (HF). Scar formation and left ventricular (LV) hypertrophy occur in response to MI to stabilize injury compensating for lost myocardial function. Over time, heart function can become decompensated due to neuroendocrine dysfunction and adverse LV remodeling, ultimately leading to HF. Adverse remodeling is characterized by continued dysregulated collagen deposition, cardiomyocyte hypertrophy, and increased inflammation. Studies have documented a resurgence in inflammatory cytokines and infiltrating leukocytes after resolution of the …

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Molecular Regulation Of Glioblastoma Spatial Heterogeneity And Therapeutic Resistance, Soniya Bastola Jan 2020

Molecular Regulation Of Glioblastoma Spatial Heterogeneity And Therapeutic Resistance, Soniya Bastola

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Glioblastoma multiforme (GBM) is a highly invasive, highly vascularized, and heterogeneous malignant tumor of the brain. Due to the highly infiltrative phenotype of GBM, surgery often leaves behind residual tumor cells. In many cases, recurrence occurs close to the surgical margin suggesting the role of these remaining cells in promoting tumor aggressiveness. Rapidly growing tumor creates subsequent hypoxic, and hypovascular core due to limited nutrients, whereas tumor cells in the leading edge have access to nutrients from vasculature enriched microenvironment. Studies have identified the cellular and molecular heterogeneity between the tumors in core and edge. Still, their mechanisms of intercellular …

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Rab27 And 14-3-3 Mediated Regulation Of Alpha-Synuclein Pathology, Rachel Nicole Underwood Jan 2020

Rab27 And 14-3-3 Mediated Regulation Of Alpha-Synuclein Pathology, Rachel Nicole Underwood

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Alpha-synuclein (αsyn) is the key component of proteinaceous aggregates termed Lewy Bodies (LBs) that pathologically define a group of disorders known as synucleinopathies, including Parkinson’s Disease (PD) and Dementia with Lewy Bodies (DLB). αSyn is thought to misfold and spread throughout the brain in a prion-like fashion. Transmission of αsyn necessitates the release of misfolded αsyn from one cell and the uptake of that αsyn by another, in which it templates the misfolding of endogenous αsyn. Identifying regulators of this process is essential to understanding how αsyn propagates and furthers disease progression. In this study, we investigated Rab27 and 14-3-3θ …

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Circadian Clock And Lipid Metabolism Disruption In Fatty Liver Disease, Jennifer Valcin Jan 2020

Circadian Clock And Lipid Metabolism Disruption In Fatty Liver Disease, Jennifer Valcin

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Hepatic Steatosis, characterized by the accumulation of triglyceride (TG) in the liver is the first stage of Alcoholic Liver Disease (ALD) and Nonalcoholic Fatty Liver Disease (NAFLD). Many metabolic pathways, including lipid metabolism, are regulated by the molecular circadian clock. Importantly, alcohol consumption and obesity induce circadian clock disruption, a risk factor for many diseases, including liver disease. In our first study, we investigated the combined effect of clock disruption and alcohol feeding on liver pathology, and diurnal rhythms in the liver molecular clock and lipid metabolism. Male liver-specific Bmal1 knockout (LKO) mice and control littermates were fed a control …

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Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk Jan 2020

Tau-Dependent Regulation Of Network Hyperexcitability By Alzheimer’S Disease Risk Gene Bin1, Yuliya Voskobiynyk

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Alzheimer’s disease (AD) is the leading neurodegenerative disorder that affects an astonishing 5.8 million Americans, a number projected to reach 14 million by the year 2050. While only about 1% of all AD cases are caused by mutations in APP, PSEN1, and PSEN2, the cause of sporadic AD remains unknown. Variations in several risk genes have been proposed to contribute to the development of sporadic AD cases. Since, currently, there are no disease-modifying therapies for families affected by AD and multiple anti-amyloid-beta therapies failed in clinical trials, determining how these risk genes contribute to the development of AD is crucial …

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The Mir-23a Cluster Controls An Epigenetic Axis In Osteoblast Development During Bone Formation, Benjamin J. Wildman Jan 2020

The Mir-23a Cluster Controls An Epigenetic Axis In Osteoblast Development During Bone Formation, Benjamin J. Wildman

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Differentiation of pre-osteoblasts is critical to controlling in-vivo development and growth of bone. Recent studies highlight the importance of epigenetic regulation in directing osteoblast commitment and function. Here we show that the microRNA-23a cluster (miR-23a, 27a, and 24-2) controls bone mass in-vivo through a previously unknown epigenetic mechanism. MiR-23a cluster knockdown increased the intensity of Alkaline Phosphatase staining in MC3T3-E1 cells. Additionally, it upregulated mRNA expression of osteogenic marker genes such as Runx2 and Osteocalcin. Micro-CT analysis of 2-month and 6-month femurs showed that trabecular bone volume and trabecular number significantly increased in miR-23aClZIP mice as compared to controls. Histological …

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Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen Jan 2020

Gene–Environment Interaction In Parkinson Disease: The Gut Microbiome, Zachary D. Wallen

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GENE–ENVIRONMENT INTERACTION IN PARKINSON DISEASE: THE GUT MICROBIOME ZACHARY D. WALLEN GENETICS, GENOMICS, AND BIOINFORMATICS ABSTRACTParkinson disease (PD) is a progressive neurodegenerative disease with no cure. Majority of cases are idiopathic, and the cause is unknown. Studies have been conducted in human and animals to identify PD risk factors, resulting in a list of genetic and environmental factors that modestly increases risk of PD. Still, no individual risk factor fully explains the cause of PD, and neither has the combination of these factors. Additional avenues of research are being investigated to find potential triggers of PD, and factors that might …

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T Cells In Synucleinopathies, Gregory Paul Williams Jan 2020

T Cells In Synucleinopathies, Gregory Paul Williams

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Synucleinopathies, which include Parkinson disease (PD), dementia with Lewy Bodies (DLB), and multiple system atrophy (MSA), are a collection of neurodegenerative diseases that are in major part defined by the presence of alpha-synuclein (α-syn) rich protein aggregates in the brain. Increasing evidence has highlighted a neuroinflammatory phenotype also associated with these synucleinopathies. This neuroinflammatory phenotype includes the activation of central nervous system (CNS) microglia, increased pro-inflammatory cytokines, and the infiltration of peripheral T cells into the CNS. We sought to further explore the T cell responses associated with PD and MSA. Using two preclinical mouse models of PD and MSA, …

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The Role Of The Viral Envelope Protein Gpul132 In Assembly Compartment Formation And Virion Production: Intracellular Lipids And/Or Cholesterol, Hui Wu Jan 2020

The Role Of The Viral Envelope Protein Gpul132 In Assembly Compartment Formation And Virion Production: Intracellular Lipids And/Or Cholesterol, Hui Wu

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Human cytomegalovirus (HCMV) is a ubiquitous pathogen that infects over 50% of the world’s population. HCMV infection is asymptomatic in healthy individuals, however can cause severe morbidity and mortality in individuals with compromised innate or adaptive immunity. As a complex virus that has been known for about 70 years, we are still in search of vaccines or effective treatments against it. HCMV genome encodes over 175 open reading frames with the function of majority proteins remains to be defined. A unique feature of HCMV among herpesvirus is the reorganization of cellular secretory pathway and membranes to form assembly compartment (AC). …

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Co-Factors In Fgf Signaling, Christopher Yanucil Jan 2020

Co-Factors In Fgf Signaling, Christopher Yanucil

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The fibroblast growth factor (FGF) family consists of a group of proteins whose diverse biological functions are mediated by receptor tyrosine kinases, termed FGF receptors (FGFR) 1-4. While paracrine FGFs require heparin sulfate as a co-factor for FGFR bind-ing and signaling, it has been assumed that endocrine FGFs, such as FGF23, do not bind heparin but instead require klotho, a family of transmembrane proteins, as a co-receptor on specific target cells. FGF23 acts as bone-derived hormone that targets tubular epitheli-al cells in the kidney via FGFR1 and α-klotho to reduce renal phosphate uptake. In chron-ic kidney disease (CKD), the kidney …

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Network-Based Analytics For Discovering Gene Modules And Biomarkers In Complex Diseases, Zongliang Yue Jan 2020

Network-Based Analytics For Discovering Gene Modules And Biomarkers In Complex Diseases, Zongliang Yue

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With rapidly increasing novel discoveries of associations between genomic data and complex disease phenotypes, the translation of those associations into knowledge and the identification of critical molecular mechanisms are essential to guild clinical decisions such as the diagnosis of symptomatic individuals, the prediction of disease risk, reproductive genetic counseling, and determining pharmacogenetic profiles for treatment. To decipher the genome of complex diseases, gene-centric analyses focus on detecting molecular mechanisms lead by driver genetics variants, abnormally expressed genes and high-abundance proteins through gene module construction. Additionally, the gene module construction approaches implement systems biology analysis to reveal the causative co-expressed gene …

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Exploring The Mechanism Of Cleavage And Secretion Of The Major Sperm Protein (Msp) Domain Of The Vapb/Vpr-1 Protein, Hala Zein-Sabatto Jan 2020

Exploring The Mechanism Of Cleavage And Secretion Of The Major Sperm Protein (Msp) Domain Of The Vapb/Vpr-1 Protein, Hala Zein-Sabatto

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VAPB is one of three mammalian VAP proteins. It is a type-II ER transmembrane protein whose N-terminal major sperm protein domain (MSPd) is cleaved and secreted. Since the MSPd faces the cytosol, rather than the ER lumen, how it is cleaved and secreted is not yet known. In humans, P56S is a substitution mutation within the VAPB protein that segregates with cases of familial Amyotrophic Lateral Sclerosis (ALS) and prevents the secretion of VAPB MSPd. The work described in this thesis uses C. elegans to study how the N-terminal MSPd of VAPB is proteolytically processed, secreted, and regulated. C. elegans …

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Circadian Control Of Blood Pressure And Renal Electrolyte Excretion, Dingguo Zhang Jan 2020

Circadian Control Of Blood Pressure And Renal Electrolyte Excretion, Dingguo Zhang

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Many physiological processes, including blood pressure (BP) regulation, follow specific rhythms tied to a 24-h cycle. This is largely because circadian genes operate in virtually every cell type in the body. In healthy individuals, BP during nighttime is 10-20% lower compared to daytime, a phenomenon known as “nocturnal dipping”. It is acknowledged that the dipping of BP is essential in maintaining normal cardiovascular and renal function. However, it remains unclear as to what factors contribute to nocturnal dipping. The purpose of this dissertation is to elucidate mechanisms underlying the circadian rhythm of BP. Bmal1 is one of the core circadian …

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Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea Jan 2020

Lim Transcriptional Complexes That Impact Endocrine Pancreas Development And Function, Maigen Bethea

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The Ldb1:Isl1 LIM transcriptional complex is critical for endocrine pancreas development as well as b-cell terminal differentiation. These complexes have been shown to interact with various proteins to elicit transcriptional regulation in other tissues, yet few interactors have been identified in b-cells. Therefore, the objective of this dissertation was to identify interactors of Ldb1 and Isl1 and assess their contributions to endocrine pancreas development and function. Using a reversible crosslink immunoprecipitation (ReCLIP) and mass spectrometry (MS) strategy to isolate endogenous Ldb1 and/or Isl1 interacting protiens, SSBP3, Rnf20, and Rnf40 (E3 ubiquitin ligases) coregulators were identified. SSBP3 was found to interact …

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Dna Methylation: A Mechanism For Sustained Alteration Of Kir4.1 Expression Following Central Nervous System Insult, Jessica Boni Jan 2020

Dna Methylation: A Mechanism For Sustained Alteration Of Kir4.1 Expression Following Central Nervous System Insult, Jessica Boni

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Astrocytes are the most numerous cells in the brain and play a critical role in maintaining homeostatic extracellular potassium ([K+]e). Maintaining low [K+]e is essential for many cellular functions including maintenance of intensely negative resting membrane potentials in the central nervous system. This process is mediated, in part, by a glial-specific, inwardly rectifying potassium channel, Kir4.1. Underscoring the role of Kir4.1 in CNS functioning, genetic mutations in Kcnj10, the gene which encodes Kir4.1, causes seizures, ataxia and developmental disability in humans. Notably, loss of Kir4.1 protein and mRNA are consistently observed after CNS injury, and in a number of neurological …

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Transcriptional, Translational, And Enzymatic Metabolic Regulation By L-2 Hyroxyglutarate, Garrett Brinkley Jan 2020

Transcriptional, Translational, And Enzymatic Metabolic Regulation By L-2 Hyroxyglutarate, Garrett Brinkley

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Recent studies have identified elevated levels of a small metabolite, L-2 Hydroxyglutare (L-2HG), which curiously has no known metabolic roles. Renal tumors, hypoxia as well as larval development, specifically in Drosophila, all have been identified to have high levels of L-2HG. These broad categories suggest L-2HG has a physiological role. This work uncovers the impact of elevated levels of L-2HG in altering normal kidney and renal tumors. With structural similarity to α-Ketoglutarate (αKG), L-2HG acts as a competitive inhibitor to enzymes that utilize αKG as substrates or co-factors. L-2HG is known to be metabolized by L-2HG dehydrogenase (L2HGDH). Loss of …

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Epigenetic Regulation In Cancer And Development, Theodore Busby Jan 2020

Epigenetic Regulation In Cancer And Development, Theodore Busby

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Feedback loops between cellular cues and changes in gene expression mediate the interactions between a multitude of regulatory events that promote development and cancer. Vesicular trafficking is an important process in carrying out signaling events by transporting receptors and ligands to and from the cell surface. GBF1 and BIG1 are large guanine-exchange factors (GEFs) that activate GTPase mediated shuttling of cargo through the Golgi apparatus. This dissertation demonstrates that GBF1 localizes to the cytoplasmic membrane in glioblastoma multiform cells to maintain cell shape and promote migration. Reports have shown that BIG1translocates to the nucleus is hepatocyte carcinoma cell lines in …

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Distinct Tissue Specific Functions Of Bone Marrow Regulatory T Cells, And Their Therapeudic Applications In Myeloid Neoplasms, Virginia Camacho Jan 2020

Distinct Tissue Specific Functions Of Bone Marrow Regulatory T Cells, And Their Therapeudic Applications In Myeloid Neoplasms, Virginia Camacho

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In the bone marrow, Regulatory T cells (Tregs) constitute nearly 30% of CD4+ T cells, a significantly higher ratio than other tissues. Although a few of the mechanisms by which Tregs regulate normal hematopoiesis have been elucidated, our understanding of this process during leukemogenesis is ex-tremely limited. In this work, we define how Tregs maintain and support the bone marrow microenvironment. We propose that the role of Tregs extends be-yond their canonical immuno-suppressive function and that these cells are re-quired to maintain healthy hematopoiesis. We have defined tissue-specific roles for Tregs in the bone marrow including the maintenance of hematopoietic …

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Abnormalities In The Akt-Mtor Signaling Pathway In The Dorsolateral Prefrontal Cortex In Schizophrenia, Radhika Chadha Jan 2020

Abnormalities In The Akt-Mtor Signaling Pathway In The Dorsolateral Prefrontal Cortex In Schizophrenia, Radhika Chadha

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Schizophrenia (SZ) is a complex and heterogeneous mental illness in which myriad changes across multiple neurotransmitter systems (dopamine, serotonin, GABA, glutamate, and others) have been reported. Numerous regulatory mechanisms have been explored in SZ research and rather than being a disorder of one specific neurotransmitter pathway, SZ may instead be a disturbance of intracellular signaling processes that underlie the regulation of these systems. The AKT-mTOR signaling cascade plays an important role in core cellular processes of cell growth, metabolism and survival and is one such potential candidate. Abnormalities in AKT expression and activity have been consistently implicated in SZ pathophysiology …

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From Pathology To Circuits: Loss Of Pink1 Function In Parkinson’S Disease, Rose Berthe Creed Jan 2020

From Pathology To Circuits: Loss Of Pink1 Function In Parkinson’S Disease, Rose Berthe Creed

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Parkinson’s disease (PD) is the most common neurogenerative motor disorder, affecting over 10 million people worldwide. Clinically, PD is diagnosed by presentation of hypokinetic movements such as bradykinesia, rigidity, and resting tremor. Additionally, PD patients have non-motor symptoms that include anosmia, constipation, and hypophonia. Current therapeutics have been successful in treating many of the locomotor symptoms, however no therapies stop or slow disease progression and the effectiveness of current medications diminishes as the symptoms invariably become more severe over the course of many years. Histopathologically, PD diagnosis is confirmed postmortem by two pathological hallmarks: 1. loss of dopaminergic neurons in …

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Enhancer Rnas As Regulators Of Gene Expression And Neuronal Function, Nancy Verena Nicole Carullo Jan 2020

Enhancer Rnas As Regulators Of Gene Expression And Neuronal Function, Nancy Verena Nicole Carullo

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Genomic enhancers are cis-regulatory elements in the DNA that exhibit spatial and temporal control over intricate gene expression programs shaping fate and function of heterogeneous cell populations in the developing and adult brain. In addition to their role in cellular development and maintenance, enhancer activity drives transcriptional changes in response to stimulation. Active enhancers are subject to bidirectional transcription that yields non-coding enhancer RNAs (eR-NAs). However, the functional role of eRNAs in transcriptional regulation remains controversial. Therefore, we used primary neuronal cultures to investigate en-hancers and eRNAs in the rat genome. We identified and verified enhancer-gene pairs, characterized their response …

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Impact Of Diet And Meal Timing On Time-Of-Day Dependent Hippocampal Function, Jennifer Davis Jan 2020

Impact Of Diet And Meal Timing On Time-Of-Day Dependent Hippocampal Function, Jennifer Davis

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Circadian rhythms are biological processes that cycle every ~24 hours and have allowed life to adapt for optimal function across the day. These rhythms are present in all tissues in the body and are coordinated to the light/dark cycle by the suprachiasmatic nucleus (SCN) in the hypothalamus. Along with active-rest cycles, cognitive performance fluctuates across the course of the day, peaking during the active phase. In addition to the light cycle, food and meal timing can provide signaling cues to extra-SCN tissues. Food access only during the inactive phase results in weight gain and memory impairment. High fat diet protocols …

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Structural Studies Of Rna Synthesis Machinery In Vesicular Stomatitis Virus, Joseph Ryan Gould Jan 2020

Structural Studies Of Rna Synthesis Machinery In Vesicular Stomatitis Virus, Joseph Ryan Gould

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Vesicular stomatitis virus (VSV) is a member of the order Mononegavirales, which is comprised of viruses with genomes of non-segmented negative sense RNA. Many fundamental insights into the molecular biology of mononegaviruses were first made in VSV, such as the unique viral RNA synthesis template comprised of the nucleocapsid (N) protein and genomic RNA and the distinctive large (L) protein which contributes all enzymatic activities of RNA synthesis and transcript maturation. The L protein performs its enzymatic functions in concert with the phosphoprotein (P), a flexible, charged, and phosphorylated cofactor. The goal of the research presented in this dissertation was …

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Il-17 Producing Cd4 T Cells In Spontaneous Germinal Center And Autoantibody Formation In Murine Lupus, Huixian Hong Jan 2020

Il-17 Producing Cd4 T Cells In Spontaneous Germinal Center And Autoantibody Formation In Murine Lupus, Huixian Hong

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IL-23 promotes autoimmune disease, including Th17 CD4 T-cell development and autoantibody (autoAb) production. Here, we show that a deficiency of the p19 component of IL-23 in the autoimmune BXD2 (BXD2-p19−/−) mouse leads to a shift of the follicular T-helper cell program from Tfh-IL-17 to Tfh-IFN-ɣ. Although the germinal center (GC) size and the number of GC B cells remained the same, BXD2-p19−/− mice exhibited a lower class-switch recombination (CSR) in the GC B cells, leading to lower serum levels of IgG2b. Single-cell transcriptomics analysis of GC B cells revealed that while Ifngr1, Il21r and Il4r genes exhibited a synchronized expression …

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Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly Jan 2020

Pharmacodynamic Responses And Efficacies Associated With Lrrk2 Inhibition, Kaela Kelly

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Parkinson’s disease (PD) is an age-related, progressive, movement disorder pathologically characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc) and the presence of proteinaceous aggregates, termed Lewy bodies, that are largely comprised of αSynuclein (αSyn). Missense mutations in the leucine-rich repeat kinase (LRRK2) gene are the most common genetic cause of PD and lead to gain-of-function increases in kinase activity. The G2019S-LRRK2 mutation is the most frequent mutation and elevates kinase activity by ~2-3 fold. Genetic and biochemical evidence suggest elevated LRRK2 kinase activity plays a pathogenic role in the development of PD, implicating LRRK2 …

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Elucidating The Role Of Hedgehog Signaling In Tumor Cell Response To Dna Damage And Microenvironmental Stress, Tshering Dolma Lama-Sherpa Jan 2020

Elucidating The Role Of Hedgehog Signaling In Tumor Cell Response To Dna Damage And Microenvironmental Stress, Tshering Dolma Lama-Sherpa

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Hypoxia within solid tumors presents as a barrier to the effectiveness of cancer treatment. Hypoxia has been implicated in cancer cell resistance to standard therapies used in the clinic to treat breast cancer. Additionally, the treatment resistance mechanisms in cancer cells are exacerbated by oncogenic pathways that enable adaptation to the hypoxia and facilitate therapy resistance. Cancer cells often co-opt signaling pathways essential for embryonic development as a defense against cellular attacks. Hedgehog (Hh) signaling pathway is one of such embryonic development pathways that have been implicated in mitigating cancer growth, metastasis, and resistance to therapy. Hh signaling pathway promotes …

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Protective Host Responses During Acute And Chronic Lung Exposure To Aspergillus Fumigatus, Joseph Mackel Jan 2020

Protective Host Responses During Acute And Chronic Lung Exposure To Aspergillus Fumigatus, Joseph Mackel

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Aspergillus fumigatus is an environmental airborne fungus that acts as both an opportunistic pathogen and an allergen. In immunocompromised hosts, A. fumigatus can germinate in the lung, cause tissue damage and pneumonia, and disseminate to other organs, causing a disease termed invasive aspergillosis (IA). In severe asthma, sensitization to fungi such as A. fumigatus is associated with more severe disease. Determination of host and fungal factors that drive immunoprotection versus immunopathogenesis in both of these settings will ultimately enable therapeutic modulation of immune responses to improve disease outcomes. In this body of work, we build on recent findings that implicate …

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