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 studies with immunodeficiency viruses, we seek to understand how the interaction of viral envelope glycoproteins with CD4 and various chemokine receptors on the target cells results in membrane fusion and viral entry. We are also developing mouse model systems to determine how HIV infection causes loss of CD4+ helper T cells. In related studies, the functions of chemokine receptors in development and in inflammatory responses are being investigated.
Helen L. and Martin S. Kimmel Professor of Molecular Immunology, Department of Pathology
Professor, Department of Microbiology
MD from Washington University at Saint Louis
PhD from Washington University at Saint Louis
Cold Spring Harbor perspectives in biology. 2017 Apr 21; ?-?
Molecular cell. 2017 Mar 3; 65(6):1068-1080.e5
Nature immunology. 2017 Feb 6; 18(4):412-421
Scientific reports. 2017 Jan 18; 7:40775-40775
Journal of antimicrobial chemotherapy. 2017 Jan; 72(1):128-136
Frontiers in immunology. 2017; 8:291-291
Cell reports. 2016 Nov 22; 17(9):2271-2285
Bio-protocol. 2016 Nov 20; 6(22):?-?