Life Sciences Commons^™

The Microbiome As An Environmental Risk Factor For Multiple Sclerosis, Theresa Montgomery

Graduate College Dissertations and Theses

Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system. The etiology of MS is complex and poorly understood; however, disease risk is likely combinatorial due to the effects of both genetics and environmental risk factors. A recently identified environment risk factor for MS is the gut microbiome. However, the specific gut microbiota associated with disease risk, onset and/or progression, their mechanisms of action, and impact of host genetics remain unclear. Leveraging the primary autoimmune mouse model of MS, experimental autoimmune encephalomyelitis (EAE), in a genetically diverse mouse model consisting of 29 unique genotypes, combined with gut …

Genetic And Functional Approaches To Understanding Autoimmune And Inflammatory Pathologies, Abbas Raza

Graduate College Dissertations and Theses

Our understanding of genetic predisposition to inflammatory and autoimmune diseases has been enhanced by large scale quantitative trait loci (QTL) linkage mapping and genome-wide association studies (GWAS). However, the resolution and interpretation of QTL linkage mapping or GWAS findings are limited. In this work, we complement genetic predictions for several human diseases including multiple sclerosis (MS) and systemic capillary leakage syndrome (SCLS) with genetic and functional data in model organisms to associate genes with phenotypes and diseases.

Focusing on MS, an autoimmune inflammatory disease of the central nervous system (CNS), we experimentally tested the effect of three of the GWAS …

Understanding The Role Of Androgen Receptor Signaling In Modulating P38-Alpha Mitogen-Activated Protein Kinase In Experimental Autoimmune Encephalomyelitis, Grace Kathryn Voorhees

Graduate College Dissertations and Theses

Multiple Sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system, characterized by axonal demyelination and multifocal inflammation. Like many autoimmune diseases, it is a sexually dimorphic disease, being 3-4 times more common in females than in males. p38α MAP kinase (MAPK) has an integral role in modulating inflammatory processes in autoimmunity. Conditionally ablating p38α MAPK in myeloid cells in B6 mice shows a sex difference in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). In the absence of sex hormones, this sex difference was reversed, suggesting a role for sex hormones in modulating p38α MAPK signaling …