Topics of interest: Cancer, Tumor immunology, Transplantation, Molecular Immunology, HIV/AIDS pathogenesis
One of the hallmarks of cancer is that they escape from being first surveyed and then eliminated by the immune system. My goal is to understand the poorly understood genetic basis of tumor immune escape using mouse models of human cancer, and, conversely, the gene network that needs to be activated in cells, in particular in stem cells and their derivatives, so that they are tolerated by the foreign immune system.
To approach these challenging questions, I am applying a positive genetic screen, in which cells are modified with immunomodulatory genes and then transferred into living mice with a reactive immune system. The survival of the transferred cells is determined with highly sensitive In vivo bioluminescence imaging. Thus, the phenotype of cell survival can be connected causally to any of the immunomodulatory genes, with which the cells had been modified. Our initial data support the notion that no single gene is able to achieve tumor immune escape and transplant tolerance, but that these are complex phenotypes that require the cooperative expression of multiple genes. More complex genetic screens are therefore needed and currently being developed. The outcomes of this endeavor will help us in the design and development of more effective cancer immunotherapies.
My other area of interest is HIV/AIDS, in particular its molecular evolution, epidemiology, drug resistance, and vaccine development. For the study of drug resistance development, I have been working with Dr. Robert Shafter and members of his lab to accelerate and refine HIV molecular diagnostics.