Toso is a cell surface molecule which prevents Fas-induced apoptosis in T Cells. Toso was discovered in the Nolan lab using retroviral delivery of cDNA molecules to Jurkat T cells followed by Fas selection. Currently we are interested in how Toso and other molecules of the apoptosis machinery maintain the balance between proliferation, cell cycle arrest, and cell death. Members working on this project are Jonathan Irish and Jeff Fortin . The elucidation of the signaling mechanism for ICAM-2 attribute a novel role for immunoglobin superfamily members in actively participating in the cumulative process of cancer and metastatic spread.
Current work is invovled in delineating signaling pathways for leukocyte adhesion mediated events.
The lab is also using genetic selection to develop a new toolset to detect and perturb intracellular events. Kevin Marks and Michael Rozinov have used phage display of peptide libraries to discover short, constrained peptides that bind to fluorescent dyes. This modular system will allow the us to routinely target a wide variety of chemicals to any locale or protein within cells. It encompasses diseases such as insulin dependent diabetes mellitus, rheumatoid arthritis, multiple sclerosis and lupus. In collaboration with the laboratories of Garrison Fathman, Ed Engleman and Larry Steinman, we are using our retroviral technologies to deliver dominant negative effectors and cytokines to block autoimmune inflammation.