The goal of my research is to elucidate the roles of apoptotic signaling pathways in the development and homeostasis of T cells. Toward this goal, I have produced transgenic mice in which specific components of these pathways have been blocked. In one transgenic line, a dominant-negative form of an adapter molecule known as FADD is expressed in developing thymocytes and mature T lymphocytes. FADD has been shown to mediate apoptotic signaling following ligation of certain nerve growth factor-/tumor necrosis factor-receptor family members. A dominant negative mutant of FADD (FADDdd) interferes with death induction following triggering of these receptors. Surprisingly, FADDdd transgenic T cells appear to undergo normal apoptosis in the thymus, but have defective development and reduced proliferation in response to antigenic stimulation. These paradoxical results suggest that the same mechanisms that control death also control survival and proliferation. Additionally, my research has demonstrated that this control is exerted at the level of the cytokine receptor/Jak/Stat pathway. The research outlined here will attempt to determine the molecular nature of this process in T cell development and homeostasis and to more broadly determine the interplay between death- and cytokine-receptor pathways.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI010454-02
Application #
6455741
Study Section
Special Emphasis Panel (ZRG1-IMB (01))
Program Officer
Prograis, Lawrence J
Project Start
2001-04-01
Project End
Budget Start
2001-04-01
Budget End
2001-07-31
Support Year
2
Fiscal Year
2001
Total Cost
$14,876
Indirect Cost
Name
University of California San Diego
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
077758407
City
La Jolla
State
CA
Country
United States
Zip Code
92093