Title

A critical role for gp96 in lymphopoiesis, thrombopoiesis, and intestinal homeostasis

Date of Completion

January 2011

Keywords

Health Sciences, Immunology

Degree

Ph.D.

Abstract

gp96 is an endoplasmic reticulum chaperone for multiple Toll-like receptors and integrins. Our lab has generated a conditional gp96 knockout model allowing gp96 to be efficiently deleted from all tissues. Herein we demonstrate that gp96 is a master chaperone for 14 of 17 hematopoietic specific integrins and the critical role for gp96 in normal B cell and T cell development, but not for myeloid cell development. Additionally, we show that gp96 chaperones the GPIb-IX complex in platelets and is critical for normal platelet development and function, and results in a condition that closely resembles human Bernard-Soulier syndrome. Lastly, we report that global deletion of gp96 in mice results in spontaneous inflammatory bowel-like disease and a surprising role for gp96 in Wnt signaling, which is known to regulate intestinal homeostasis. Thus, my thesis work was aimed at understanding the roles and mechanisms of gp96 in (1) hematopoiesis, (2) platelet development and function, and (3) intestinal homeostasis. ^