In the 1920s, Otto H. Warburg discovered the metabolic hallmark of cancer: the Warburg effect. It describes that tumor cells have a high glucose consumption rate and produce large amounts of lactate.. It was difficult to understand why tumor cells need the Warburg effect since the generation and excretion of lactate would appear be a waste of carbon backbone and energy that is needed for proliferation. In one of Warburg’s milestone reviews, he proposed that the cause of the Warburg effect was injury of respiration and the consequence, cell dedifferentiation.  At that time, he was aware that inhibition of respiration led to metabolic reprograming and insightfully proposed a connection between metabolic reprograming and cell dedifferentiation, the underlying mechanism was unclear due to limited understanding of the connection between metabolism and epigenetic control.  

Our lab is interested in understanding how does metabolic reprogramming  induce the Warburg effect to alter epigenetic landscape in cancer cells and developing metabolic intervention strategies to overcome tumor resistance to differentiation therapy.