Dr. Jing Chen Laboratory

Our Research

Lifestyle choices such as diet and physical activity significantly affect risk for cancer. However, since most of the epidemiological studies do not control for specific genetic backgrounds, a pathogenic link between diets and particular oncogenic mutations remains unknown. In addition, dietary advice and dietary supplement choice are typically not based on an individual’s specific genetic background, thus the identity and action mechanisms are unclear of circulating diet-derived nutrients and dietary supplements that are defined as “blood chemicals” and affect oncogenesis involving oncogenic mutations or carcinogens that “battery-charge” oncogenic mutations. Our metabolic signaling-based studies to date strongly support the overarching goal of this research proposal that mechanistic understanding of oncogene-specific metabolic requirements and their pathogenic consequences in cancer holds promise for defining the pathogenic links between diet and cancer. These studies are rooted in new discoveries made by our group that dietary fat-dueled ketogenesis plays a pathogenic role in BRAF V600E tumor growth, where mechanistically ketone body acetoacetate selectively promotes BRAF V600E-MEK1 binding, and that dietary supplements may exhibit oncogene-specific pro-tumor effects. Thus, we are rigorously pursuing two broad questions: (1) What are intracellular oncogene-specific metabolic requirements and how do related diets fuel tumor growth driven by particular oncogenes? (2) Which extracellular circulating diet-derived nutrients, supplements, and other human “blood chemicals” facilitate or attenuate oncogenesis involving oncogenic mutations or “battery–charging” carcinogens and what are their action mechanisms? We believe that our studies will not only inform development of metabolism-targeted therapeutic strategies and provide mechanism-driven rationales for clinical and epidemiological studies, but also allow physicians or pharmacists to consider an individual’s specific genetic background to provide reliable advice for diet or dietary supplement choices with low cancer risk, and educate people to seek advice from informed resources, since many people “self-prescribe” dietary supplements.