Dan R. Littman

Board Member: 1997 - 2000

Current Institution
New York University
Skirball Institute of Biomolecular Medicine

Scholar: 1986

Awarded Institution
University of California, San Francisco


Research Interests

T-Lymphocyte Development and Retroviral Pathogenesis

Our laboratory investigates 1) the molecular events underlying T-lymphocyte differentiation and activation and 2) how the human immunodeficiency virus (HIV) enters target cells and causes systemic depletion of helper T cells. In both areas, we study the functions of T-cell surface molecules and their interactions with intracellular signal transducing components.

During development, CD4 and CD8 glycoproteins are co-expressed on immature thymocytes (double-positive cells), which are then selected according to their ability to interact productively with host major histocompatibility complex (MHC) molecules expressed on thymic epithelium. Cells with T-cell receptors specific for MHC class I shut off CD4 and commit to becoming cytotoxic cells, while cells with T-cell receptors for MHC class II shut off CD8 and become helper cells. We use gene targeting and transgenic technology in mice to study how the double-positive cells commit to either of the two major T-lymphocyte lineages.

In our viral-entry studies, we seek to identify host-cell genes other than CD4 that are required for HIV to fuse to target-cell membranes and become internalized. We are also developing mouse-model systems to determine how HIV infection causes loss of CD4+ helper T cells. We use similar approaches to identify receptors for the human T-cell leukemia viruses, HTLV-1 and HTLV-2, and to develop a model system for HTLV pathogenesis.