All ETDs from UAB

Advisory Committee Chair

Louis B Nabors

Advisory Committee Members

Scott R Barnum

Peter H King

Harold W Sontheimer

Linda O Wadiche

Document Type

Dissertation

Date of Award

2013

Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine

Abstract

In inflammatory diseases of the central nervous system (CNS), astrocytes play a major role in the systemic response to disease by either enhancing or limiting the inflammatory response through secretion of growth factors or cytokines. HuR RNA binding protein regulates many genes involved in inflammation. Inflammatory diseases such as brain tumors, Amylotrophic Lateral Sclerosis (ALS), and Multiple Sclerosis (MS), have been linked to HuR, by our laboratory and others. To determine whether astrocytic overexpression of HuR would regulate inflammation in diseases of the CNS, we designed a transgenic mouse in which the HuR gene is overexpressed. In the first study, we used this transgenic mouse model to understand how HuR regulates the disease course of Experimental Autoimmune Encephalomyelitis (EAE), a mouse model to study MS. In the second study, we implanted GL261 brain tumor cells in the transgenic mouse to examine how an overexpression of HuR affects the peripheral immune cells in a syngeneic tumor mouse model. Creation of this mouse model supplies us with a new tool to understand how HuR regulation through astrocytes impacts multiple disease models.

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