Man’s research focuses on studying the mechanism of the aberrant regulation of intracellular pH and potential therapeutic targets via pH manipulation in acute myeloid leukemia (AML), a fatal and heterogeneous disease with a low cure rate despite the establishment of current treatment strategies, such as conventional chemotherapy and bone marrow transplantation.
From his previous data, AMLs usually exhibit a more alkali intracellular pH than that of normal blood cells. Increase in pHi has been suggested to be oncogenic in several biological activities, such as promoting cell proliferation, glycolytic metabolism and invasiveness and limiting apoptosis of cancer cells. The increased pHi of cancer cells is paradoxical as higher rate of proliferation and glycolysis should produce much metabolic acids. However, many cancers exhibit elevated expression/activity of proteins which facilitate H+ efflux and maintain the increased pHi. Therapeutic targeting these proteins via suppressing H+ efflux and thus reducing pHi have been suggested to be cytotoxic to many different cancers. However, a comprehensive analysis of pHi homeostasis and its molecular mechanism in AML are the missing pieces and therefore serve the basis of his research topic.
Based on the fact that AML generally exhibit high pHi and the hypothesis that AML is highly dependent the alkaline pHi for its survival, He suggests that targeting the aberrant pH homeostasis in AML has provided an attractive and universal therapeutic window.