PROMOTING SCIENCE AND TECHNOLOGY BETWEEN INDIA AND THE U.S.
Biology, Cancer Research, Medicine
Massachusetts Institute of Technology
Our laboratory is interested in understanding how specific anatomical sites can be inherently chemoprotective, without presenting a physical barrier to drug delivery. Our recent work has identified mechanisms by which front-line anti-cancer regimens can target most cancer cells yet, paradoxically, promote the survival of a residual tumor burden in specific microenvironments. This process involves the induction of a carefully regulated pro-survival paracrine signaling program emanating from proximal endothelial and infiltrating immune cells. These discoveries have laid a foundation to study basic mechanisms of disease persistence following chemotherapy. For example, our work has shown that the same mechanisms used to protect stem and progenitor cells from physiological stresses can be coopted by tumor cells to evade systemic drug regimens. Thus, we have been able to apply basic tenants of stem cell and developmental biology to direct hypothesis-driven experiments in the realm of cancer therapy – a field that is notoriously reliant upon empirical data. Importantly, these experiments have also involved the development of new tractable tumor transplantation models in which cancer cells can be rapidly and extensively modified ex vivo and then transplanted into syngeneic, immunocompetent recipient mice. In the process of developing these pre-clinical models, our laboratory has pioneered the application of rapid loss of function screening approaches for use in vivo in mouse models of cancer. Results from these studies have highlighted significant barriers to therapeutic efficacy, but have also identified new targets that, when inhibited, can potentiate the effects of currently used drug regimens.