dlw002

David L. Wiest, PhD

Contact Dr. Wiest

333 Cottman Avenue
Fox Chase Cancer Center 333
Philadelphia, PA 19111

(215) 728-2966
(215) 728-2412 fax

Research and Clinical Interests

T lymphocytes recognize and destroy invading pathogens through an assembly of proteins called the T cell antigen receptor (TCR) complex. The TCR has protein subunits that are highly variable and responsible for target recognition (either alpha-beta or gamma-delta) and subunits that are invariant proteins and serve to transmit signals (CD3gamma, delta, epsilon and zeta). This critical protein assembly (the TCR) controls not only the behavior of mature T lymphocytes but also their development in the thymus. My laboratory seeks to understand how T cell development is controlled by the TCR and how these developmental process are corrupted during development of cancer. As indicated above, there are two types of TCR variable proteins, alpha-beta and gamma-delta. Utilization of these alpha-beta and gamma-delta pairs characterizes two distinct types of T lineages, alpha-beta and gamma-delta, respectively. These two T lineages are thought to arise from a single immature precursor in the thymus. We are attempting to identify the cellular factors that are essential for transmitting the signals that direct fate adoption (i.e., alpha-beta and gamma-delta). We are also interested in identifying the downstream molecular targets of those signals that are essential for development of these two different T cell types. We hypothesize that genes, which are essential for normal cell development, are also likely to regulate development of cancer. Indeed, we have recently identified such a gene, which encodes a component of a cellular machine used to synthesize all cellular proteins. This component, termed Rpl22, is not only essential for normal T cell development, but also may contribute to development of human T cell cancers termed T acute lymphoblastic leukemia (T-ALL).