Dr. Wolfe studies KRAS, a cancer-promoting protein that is activated by mutations in most forms of cancer. Tumor cells can become “addicted” to the presence of overactive KRAS protein, such that they die when KRAS is suddenly removed. He will focus his research on an exciting new class of inhibitors that cause active KRAS to be rapidly degraded. He aims to explore the effects of depleting KRAS on cancer cells, understand the mechanism by which these novel KRAS inhibitor drugs cause the protein to be degraded, and optimize the efficacy of these drugs. Understanding which drug combinations are most effective and which patients are most likely to be helped by KRAS depletion are critical steps for improving patient outcomes. The results of this research are expected to have a major positive impact because they will a) expand our knowledge of tumors’ reliance on KRAS, and b) characterize the effects of this novel class of cancer therapeutics against active KRAS, a critical target driving many forms of cancer.