Position title: Professor of Medicine and Chief, Div. of Endocrinology
I lead a multidisciplinary team of scientists who focus on understanding how tumors adapt to and survive metabolic stress. We are particularly interested in translating these insights into improved biomarkers and therapies. Our team has developed a novel therapeutic paradigm to metabolically prime breast tumors to proapoptotic therapy using dietary methionine restriction (MR). My lab demonstrated that dietary MR enhances the antitumor activity of proapoptotic TRAIL receptor agonists by increasing cell surface expression of TRAIL receptor-2 in tumors. These laboratory discoveries have led to two clinical trials of dietary MR to examine its tumor and metabolic effects in newly diagnosed TNBC (NCT03186937) and its activity in combination with a novel TRAIL agonist (ONC201) in patients with metastatic TNBC (NCT03733119). We have also collaborated with the Lamming lab to demonstrate the metabolic effects of methionine restriction in mice. To this end, we demonstrated in collaborative studies that MR causes a dramatic reduction in adiposity and improves glucose homeostasis in a murine model of obesity. We are currently investigating the underlying mechanisms by which MR inhibits tumor growth and improves metabolic health and exploring the translation of these findings in clinical trials.