As the king of tumor suppressors, p53 plays a central role in tumor prevention. p53 is the most frequently-mutated gene in human tumors; over 50% of all human tumors harbor p53 mutations, and over 80% of tumors have p53 dysfunction. As a transcription factor, p53 regulates a wide variety of cellular responses, including cell cycle arrest, apoptosis, senescence, metabolism, autophagy, ferroptosis and immune response, to exert its function in tumor suppression. Given its critical role in cancer, p53 has attracted tremendous studies and become an extremely attractive target for cancer therapy. One of our main research interests is to study the mechanism of p53 in tumor suppression and how it can be targeted for cancer therapy. We study new regulators and new regulation mechanisms for p53 and its signaling pathway, such as new E3 ubiquitin ligases, microRNAs and Sumoylation modification that regulate p53 and its signaling pathway. Furthermore, many tumor-associated mutant p53 proteins often gain new oncogenic activities in promoting tumorigenesis in addition to loss of wild-type p53 function in tumor suppression, which is defined as mutant p53 gain-of-function. We study the mechanism underlying the mutant p53 gain-of-function in tumorigenesis and how to target mutant p53 for cancer therapy.
Metabolic reprogramming is a hallmark of cancer cells and a key contributor to cancer initiation and progression, which can be targeted for cancer therapy. Another main research interest of our lab is to study the mechanism of metabolic reprogramming in cancer and how it can be targeted for therapy. We study how cellular metabolism, including metabolism of glucose, lipids, and amino acids are regulated by tumor suppressors (e.g. p53, Parkin, GLS2, CUL3), oncogenes, protein modifications (e.g. ubiquitination, Sumoylation, phosphorylation, acetylation, etc.), and the tumor microenvironment (e.g. hypoxia, inflammation, stroma and immune cells). Furthermore, we study how these metabolic changes affect cancer initiation and progression, and how they can be targeted for cancer therapy.