GSBS Dissertations and Theses

Approval Date

6-10-2016

Document Type

Doctoral Dissertation

Academic Program

Immunology and Microbiology

Department

Medicine

First Thesis Advisor

Robert Finberg, M.D.

Second Thesis Advisor

Jennifer Wang, MD

Keywords

Type 1 Diabetes Mellitus, Innate Immunity, Insulin, Insulin-Secreting Cells

Subjects

Dissertations, UMMS; Diabetes Mellitus, Type 1; Immunity, Innate; Insulin; Insulin-Secreting Cells

Abstract

The increasing healthcare burden of type 1 diabetes (T1D) makes finding preventive or therapeutic strategies a global priority. This chronic disease is characterized by the autoimmune destruction of the insulin-producing β cells. This destruction leads to poorly controlled blood glucose and accompanying life threatening acute and chronic complications. The role of viral infections as initiating factors for T1D is probable, but contentious. Therefore, my goal is to better characterize the effects of viral infection on human β cells in their function of producing insulin and to define innate immune gene responses in β cells upon viral infection. These aspects were evaluated in various platforms including mice engrafted with primary human islets, cultured primary human islets, β cells derived from human stem cells, and a human β cell line. Furthermore, the contributions of cell-type specific innate immune responses are evaluated in flow cytometry-sorted primary human islet cells. Taken together, the results from these studies provide insights into the mechanisms of the loss of insulin production in β cells during virus infection, and characterize the antiviral innate immune responses that may contribute to the autoimmune destruction of these cells in T1D.

DOI

10.13028/M2DW2K

Rights and Permissions

Copyright is held by the author, with all rights reserved.

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