Lymphocyte development involves both bHLH family transcription factors, such as E proteins, and their negative regulators, namely Id, Hes and Tal1 proteins. Loss of E protein function blocks lymphocyte development at early stages and promotes tumorigenesis. We propose to evaluate immunodeficiency and lymphomagenesis models generated from known regulators of E protein function. Specifically, we will generate mice that express the E protein inhibitor Id1 under the control of the murine CD4 promoter. We will then assay the role of E proteins on thymocyte signaling and in positive and negative selection process. In addition, as the CD4 promoter will drive expression of Id1 in mature CD4+ T cells, we will elucidate potential functions of E proteins in peripheral T cell signaling pathways. Furthermore, we will investigate the development and function of CD4+ T helper subsets. Lastly, we will seek to determine whether the tumorigenic potential of Id1 is dependent on loss of E protein function at the double negative stage of T cell development by comparing tumorigenesis in mice that express Id1 under control of either Ick or CD4 promoters.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32AI065211-03
Application #
7258919
Study Section
Special Emphasis Panel (ZRG1-F07 (20))
Program Officer
Prograis, Lawrence J
Project Start
2005-07-01
Project End
2008-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$50,428
Indirect Cost
Name
Oklahoma Medical Research Foundation
Department
Type
DUNS #
077333797
City
Oklahoma City
State
OK
Country
United States
Zip Code
73104