Genetics and Genomics Commons^™

Mutations In Ikaros Lead To An Altered Epigenetic And Chromatin Landscape Contributing To The Manifestation Of B-Cell Related Disorders, Princess Rodriguez

Graduate College Dissertations and Theses

IKAROS is expressed throughout the entire hematopoietic system and is required for lymphoid commitment and subsequent differentiation towards the B-lymphoid fate. If absent, progenitor and mature B-cell subsets are not expressed. IKAROS (encoded by IKZF1) is a zinc-finger transcription factor shown to regulate gene expression either directly or through the recruitment of chromatin remodeling complexes. The epigenetic gene regulatory mechanisms, including the posttranslational modification to histone proteins, as well as the expression of noncoding RNAs (ncRNAs) are important to control as perturbations in these processes contribute to the manifestation of human diseases. If left unregulated, uncontrolled growth, aberrant cell activation, …

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 …

The Cardiovascular Epidemiology And Genome-Wide Associations Of Biomarkers Of Innate And Adaptive Immunity: Scd163 And Sil2ra, Jon Peter Durda

Graduate College Dissertations and Theses

Cardiovascular disease (CVD) is a major cause of morbidity and mortality in the U.S. and worldwide. Atherosclerosis, the buildup of plaque in the arteries, is a common cause of CVD. For many years, research in atherosclerosis was focused on lipid metabolism and the accumulation of low-density lipoprotein in the arteries. While this research set public health guidelines for lipid management, lipid concentration was not the only factor influencing atherosclerosis and CVD events. Many scientists, as far back as the 1850’s recognized the role of inflammation in the progression of atherosclerotic disease. The continuous low levels of immune activation in the …