Medicine and Health Sciences Commons^™

Mechanisms And Consequences Of Myb Gene Activation In Salivary Gland Tumors, Candace Frerich

Biomedical Sciences ETDs

Salivary gland adenoid cystic carcinoma (ACC) is an aggressive tumor with a tendency to infiltrate surrounding nerves and metastasize to distant sites. The standard treatment often fails to control local tumor recurrence and distant metastases and no approved targeted therapeutic options exist for these tumors. The goal of our studies was to reveal the molecular mechanisms driving ACC tumor development and novel drug targets to improve patient morbidity and mortality.

We first analyzed clinical and RNA-sequencing (RNA-seq) data for 68 formalin-fixed paraffin-embedded (FFPE) ACC tumor samples and described previously unappreciated molecular heterogeneity that predicts patient outcome. The poor outcome subgroup …

Neuron Specific Gene 2 (Nsg2): A Novel Regulator Of Excitatory Neurotransmission Via Ampa Receptor Trafficking At A Subset Of Glutamatergic Synapses, Praveen Chander

Biomedical Sciences ETDs

Members of the Neuron-Specific Gene family (NSG1-3) play critical roles in excitatory synaptic transmission via regulation of AMPA receptor surface expression within the post-synaptic density (PSD). While NSG1 and NSG3 regulate AMPAR recycling and endocytosis, respectively, the function of NSG2 has remained elusive. Here we undertook a series of studies to assess the role of NSG2 in excitatory synaptic transmission. We found that a portion of NSG2 punctae localized with HOMER1 and surface AMPARs at excitatory synapses and that NSG2 AMPAR subunits in mouse brain. Knockout of NSG2 selectively impaired the frequency of AMPA mEPSCs, while overexpression caused a significant …

The Role Of Omega-3 Polyunsaturated Fatty Acids In Blood Pressure Regulation And Secondhand Smoke-Induced Vascular Dysfunction, Emily Anna Wheeler

Biomedical Sciences ETDs

Omega-3 polyunsaturated fatty acids (n-3 PUFAs) may lower cardiovascular disease risk by reducing blood pressure (BP). We hypothesized that fat-1 transgenic mice, which convert n-6 PUFAs to n-3 PUFAs, would have improved vascular function in BP regulation and following secondhand smoke (SHS) exposure, compared to wild type (WT) mice.

BP was recorded in mice fed an n-6 PUFA, or standard chow diet. On the n-6 PUFA diet fat-1 mice had a lower mean arterial pressure and a greater decrease in diastolic BP when treated with an ACE inhibitor, compared to WT mice. No differences were observed on the chow diet. …

The Role Of Adaptive Immunity In Chronic Hypoxia-Induced Pulmonary Hypertension, Levi David Maston

Biomedical Sciences ETDs

Inflammation is a prominent pathologic feature in pulmonary arterial hypertension as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension (PH) caused by chronic hypoxia (CH). Inflammatory cells, through various mechanisms, have the capability to increase pulmonary vascular resistance in various disease states. CD4⁺T cells have the potential to play a significant role in the disease process initiated by hypoxia. CD4⁺T cells are largely responsible for orchestrating downstream immune processes and are critical in focusing and amplifying …

Intratypic Genetic Variability Of Human Adenovirus Type 4: Implication For Viral Pathogenesis, Camden Roy Bair

Biomedical Sciences ETDs

Human adenovirus type 4 (HAdV-E4) is a causative agent of acute respiratory disease and conjunctivitis worldwide. Two major lineages of HAdV-E4 genomic variants have been identified by their distinct BamHI restriction profiles: prototype-like (p-like) strains and the a-like genomic variants. Recent molecular epidemiology studies have shown a predominance of a-like genomic variants detected in association with disease which suggests a-like strains have a fitness advantage or they may be more pathogenic. The impact of HAdV-E4 intratypic genetic variability on in vitro and in vivo phenotypes relevant to pathogenesis is a major gap in knowledge. I hypothesize that HAdV-E4 comprises two …

Determining The Pathological Effects Of Prenatal Alcohol Exposure On Peripheral Neuropathy Via Spinal And Peripheral Immune Mechanisms, Joshua J. Sanchez

Biomedical Sciences ETDs

Previous studies have suggested that children with Fetal Alcohol Spectrum Disorder (FASD) display hypersensitivity to light touch. In support of this notion, we have demonstrated that applying a chronic constriction injury (CCI) to the sciatic nerve of rats that have prenatal alcohol exposure (PAE) results in heightened sensitivity to light touch, clinically termed allodynia. These observations coincided with heightened glial activation and enhanced peripheral immune reactivity. Considering allodynia is known to be mediated by both peripheral immune responses and spinal glial activation, it is reasonable to speculate that allodynia following PAE may be mediated through an alteration of immune reactivity. …

Determining Mediators Of Naive T Cell Motility And Dc Association In The Lymph Node, Janie R. Byrum

Biomedical Sciences ETDs

To become activated and perform effector functions, naive T cells move within lymph nodes to scan dendritic cells presenting antigen. Previous work has shown naive T cell activation is promoted by interleukin 7 in vivo, and it does so by regulating the T cell:dendritic cell interaction. Our work identifies a novel role for IL-7 in mediating naive T cell motility in the lymph node and promoting T cell association with DCs. Additionally, we have developed a method for analyzing microscopy images, regionalized normalized mutual information, to assess intercellular associations between T cells and other cells within the lymph node. Dendritic …