Ph.D., 1963, Rockefeller University 1975 Recipient of Nobel Prize in Physiology or Medicine
Signal Transduction, Transcriptional Regulation and Cell Cycle Controls
Our laboratory is involved in three major directions of research.
The first is study of the remarkable range of activity of the NF-kB transcription factor. It activates perhaps 1000 genes in response to a wide range of stimuli. It has different physiologic roles in different cells. How one factor can be so varied in its activity is the puzzle that interests us. We are studying this at the level of DNA-protein interactions as well as signal transduction pathways. We are studying its role in normal cells and in diseases like cancer and AIDS.
The second line of work involves using gene transfer methods to reprogram the immune system. We have shown that we can design a retrovirus vector able to express cDNA’s encoding both chains of the T cell receptor (TCR) protein. When mouse hematopoietic stem cells are transduced with the vector and then inoculated into irradiated mice, many of the resulting T cells express the TCR encoded by the vector. We have shown that when the TCR is able to recognize specific peptides from a tumor antigen, the animal can reject tumors carrying the antigen. We plan to extend these studies to human tumor antigens with the goal of developing a human therapy. We are also studying whether the same strategy will work for antibody gene expression by B cells with a goal of devising a new therapy for AIDS.
The third goal of the laboratory is to understand the role of the Ryk protein as a co-receptor for Wnt proteins. We have shown that Wnt interacts with both Ryk and Frizzled surface receptor proteins in a tripartite complex. We are now investigating the pathways activated by Ryk and the role of Ryk in neuronal guidance.
Last modified 2012-04-03 09:12 AM