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Thomas J. Sayers, Ph.D.
Identification of Factors Involved in Tumor Cell Destruction by the Immune System
Cytotoxic lymphocytes destroy tumor cells in vitro using 2 main mechanisms: (1) by the release of lytic granules from the lymphoid cells that contain toxic proteins including the pore-forming protein perforin as well as a family of enzymes known as granzymes (2) by the production of 'death ligands' of the TNF family which can trigger tumor cell suicide (apoptosis). The relative importance of these mechanisms for antitumor effects in vivo is being studied. Our current studies are also concentrated on identifying the molecular events underlying tumor cell death, with a focus on rapidly developing knowledge of mechanism(s) of apoptosis. We are studying a possible role for the 'death ligands' Fas-ligand, TNFalpha, and TRAIL in immune-mediated destruction of tumor cells in vivo and their role in controlling the development of tumor metastases. In addition, we are assessing the ability of some drugs to sensitize tumor cells to death ligands and the molecular basis of this sensitization. More recently we have attempted to isolate minor subpopulations of cancer stem cells using DNA constructs where green fluorescent protein is responsive to the embryonic transcription factor Nanog. Our overall goal is to better understand the molecular events operating during tumor cell death in tumor cells in various sttes of differentiation. This knowledge should be useful in the rational design of agents to trigger these 'suicide' pathways in tumor cells.
This page was last updated on 5/21/2014.