Dr. Jing Chen Laboratory

Our Research

The terms metabolic "reprogramming" and "rewiring" have emerged to describe the increasingly emphasized metabolic changes in cancer cells. However, they have been used interchangeably without appreciation for their mechanistic distinction and biological implications. Dr. Chen and his team were the first to clearly define and distinguish them. They have accomplished a series of work that lays the foundation for a novel notion that "metabolic reprogramming" should represent "software" changes in cancer cells and describe metabolic alterations that are normally induced by growth factors in proliferating cells, but "hijacked" by oncogenic signals; and "metabolic rewiring" should represent "hardware" changes and describe newly "forged" metabolic alterations due to "neo-function" of distinct oncogenic mutants, which are not found in normal cells. Thus, they propose that oncogenic mutations reprogram and rewire metabolic pathways, which could be "fueled" by diet/nutrition, providing a proliferative advantage to cancer. Clearly distinguishing and characterizing metabolic "reprogramming" and "rewiring" in cancer cells will particularly inform therapy development as apparently targeting new "wiring" (e.g. IDH mutant inhibitors) in cancer cells will have minimal toxicity to normal cells. Moreover, exploring pathogenic links between diet and cancer patients harboring particular oncogenic mutations will provide new insights into development of a new concept that they named as "precision diet", which is specifically designed based on individual genetic background, including "personalized" diet with low cancer risk and "diet therapy" providing cancer prevention.

Their goal is to transition these novel approaches to a point where clinical benefit can be achieved for cancer patients through improved lifestyle and treatment. Three major directions include (1) Targeting mutation-specific, "synthetic lethal" metabolic partners and related "rewired" pathways in cancer; (2) Targeting diet-fueled metabolic "rewiring" in cancer; and (3) Targeting "reprogrammed" metal ion homeostasis and metabolism in cancer.