Classical oncogenic genetic events like activating point mutations in KRAS or amplification of MYC drive sporadic cancers. If we had the ability to potently and specifically target tumor cells with these OGs, we would have better anti-cancer therapies with reduced toxicity to non-tumor cells. Using combinations of whole genome CRISPR and essential gene shRNA libraries in isogenic cell lines differing only by the presence or absence of a tumor driver, our lab has identified many genes and protein networks required for either MYC amplified or KRAS mutant cell growth but are dispensable for normal cell growth. Future research including in vivo tumor systems will examine if these genes represent potential anti-cancer therapies and identify novel combination therapies to treat tumors.

Tumor evolution is a complex adaptive process that involves alterations in many cellular functions including cell differentiation status, telomere maintenance, cell proliferation control, adaptation to altered nutritional states, evolution of angiogenesis capabilities, avoidance of cell death, adaptation to proteotoxic and genomic stressors, etc. A major hurdle to tumor formation is the body’s immune system. The immune system can treat tumor as an emerging pathogen unleashing a response that aims to eliminate the tumor, thereby selecting for genetic alterations that result in immune surveillance adaptation. Understanding how different common cancer drivers contribute to immune system avoidance is still largely unknown. We’ve used syngeneic tumor models to perform CRISPR and cDNA-based genetic screens in vitro and as tumor transplants in vivo in both immunocompetent and immunocompromised mice that lack an adaptive immune system. The results from these experiments have identified both TSGs and OGs that contribute to tumor immune evasion. Current research in the lab aims to mechanistically identify how these genes affect tumor immune surveillance with the goal of reversing their effects helping to reignite the immune system to more effectively kill tumor cells.