Life Sciences Commons^™

Regulation Of Neuroinflammation After Ischemic Stroke By Astroglial Endothelin Receptor Type-B Signaling, John Mcinnis

Graduate College Dissertations and Theses

A large body of neuroscientific research has focused on reactive gliosis and glial scar formation because these are among the most prominent features of the cellular response to central nervous system (CNS) injury. Despite much progress in our understanding, controversy remains regarding the relative balance between the protective nature of the astroglial scar and its anti-regenerative features. Recent work suggests that astrocytes are heterogeneous in their resting state and in their reactivity. In traumatic injuries such as stroke and spinal cord injury, proliferative reactive astrocytes protect CNS tissue. By contrast, under neuroinflammatory and/or neurodegenerative conditions, neurotoxic astrocyte phenotypes may contribute …

Redox Regulation Of Src Kinase: Implications For Innate Il-33 Signaling In Allergen Responses, Christopher Michael Dustin

Graduate College Dissertations and Theses

The proto-oncogene tyrosine kinase Src is a ubiquitously expressed non-receptor tyrosine kinase involved in critical cellular functions including wound healing, migration, survival, and proliferation. Accordingly, aberrant Src signaling is also significantly involved in many diseases. Src is most well known as an oncogenic protein, however, there are emerging roles for Src signaling in various tissues involved in inflammatory diseases. One such tissue is the respiratory epithelium, which comprises the first line of defense against inhaled microbial, particulate, and chemical insults and is a critical nexus of innate immune signaling. Recent work has detailed the involvement of Src in many innate …

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 …