Topics of interest: Cancer, Tumor immunology, Transplantation, Molecular Immunology, HIV/AIDS pathogenesis
One of the hallmarks of cancer cells is that they escape from being surveyed and eliminated by the immune system. My goal is to investigate the genetic basis of tumor immune escape using mouse models of human cancer, and, conversely, the gene network that confers on cells, in particular stem cells and their derivatives, immune privilege so that they are tolerated by a reactive (allogeneic and/or autoimmune) immune system.
To approach these challenging questions, I have designed a positive genetic screen, in which cells are modified with immunomodulatory genes and then transferred into living mice. The subsequent survival of the gene-modified cells is determined with highly sensitive In vivo bioluminescence imaging. The phenotype of cell survival can therefore be connected causally to any of the transferred immunomodulatory genes.
Our initial data show that no single immunomodulatory gene or two gene combination is able to achieve tumor immune escape and transplant tolerance, Rather, these phenotypes are quite complex and must require the cooperative expression of multiple genes. Genetic screens of higher order complexity are therefore needed and currently being developed. The results of this endeavor will help us in the design and development of more effective cancer immunotherapies and in the improved induction of operational transplant tolerance.
My second area of interest is HIV/AIDS, in particular its molecular evolution, epidemiology, drug resistance, and vaccine development. For this, I have been collaborating for several years now with Dr. Robert Shafter and members of his lab to accelerate and refine HIV molecular diagnostics.