The unifying theme of our research program is to uncover the mechanisms of genetic complexity in cancer, and to use natural genetic diversity to discover new cancer drivers. Central to our strategy is the ability to integrate murine and human biology through comparative genomics and computational modeling. The iterative mouse-human, and in silico-laboratory experimentation uncovers new findings and refine contemporary assumptions. This new understanding will lead to innovative therapeutic approaches for both prevention and treatment of cancer. Select scientific initiatives supporting these goals include:
Genetic complexity of cancer and of the host are among critical barriers to improving efficacy of cancer treatment. The diversity of mutations in each cancer type limits the development of a common therapeutic; the clonal variation and genetic instability engenders resistance to any therapy; and the genetic diversity between patients contributes to varied responses to any single treatment. Furthermore, the impact of host genetics on cancer initiation, progression, and response to treatment is poorly understood. We surmise that basic biology will enable us to comprehend and then harness and exploit this complexity to find new and novel treatment strategies (for example new targets, new therapeutic agents, novel drug combinations) that will halt cancer progression and enable long-term survival of the patients.