Xiao-Mei Qi, MD

Dr. Qi's Faculty Collaboration Database

Cancer is a leading cause of human death and development of better therapeutics is a major task for cancer research. Nuclear receptors are a group of proteins that act as transcription factors to regulate gene expression in response to ligand treatment. Our major research interest is to explore novel functions of nuclear receptors in regulating therapeutic stress response by dissecting their signaling cross-talk with stress MAPKs.

Our studies have established that vitamin D receptor (VDR) is a stress responsive protein and its expression is induced by stress signaling through c-Jun/AP-1 pathways, which in turn inhibits stress-induced cell death. In human colon cancer cells, K-Ras mutation was shown to inactivate the VDR stress-regulatory pathway leading to an increased cell-death in response to stress p38 MAPK activation. In human breast cancer cells, on the other hand, our studies showed that estrogen receptor (ER) may inhibit stress-induced c-Jun-dependent cell death through a direct protein-protein interaction. These results together suggest that nuclear receptor VDR and ER may have dual biological roles: in response to ligand, they act as a receptor to mediate ligand-induced specific response through transcriptional regulations; in response to stress they function as a cell-death inhibitor through interacting and/or cross-talking with c-Jun-dependent pathways. Regulation of VDR/ER activity may consequently correspond to a novel strategy to increase cancer therapeutic response.