Guest Speaker:  Kezhong Zhang, Ph.D., Distinguished Professor, Department of Biochemistry, Microbiology and Immunology, Wayne State University 

The Research in Zhang Lab is focused on molecular mechanisms and physiological roles of cellular stress signaling from the endoplasmic reticulum (ER) or mitochondria in inflammation and metabolism associated with metabolic disease, autoimmune disease, and cancer. Related to cancer research, the lab has been studying roles and mechanisms by which ER stress sensors or ER lipid-raft proteins promote oncogenesis or therapy resistance in breast cancer or hepatocellular carcinoma (HCC). Our studies identified that the ER lipid raft-associated protein 2 (ERLIN2) and the primary Unfolded Protein Response (UPR) transducer IRE1α plays supporting oncogenic roles by facilitating cancer cell adaptation to oncogenesis-associated cellular stress. Oncogenic ERLIN2 confers growth advantage and stress-resistance capabilities to breast cancer cells by facilitating de novo lipogenesis and cytosolic lipid droplet accumulation upon the treatment of anti-cancer drugs (Biochem. J 2012; Cell Discovery 2015). Further, we defined that the UPR transducer IRE1α, a kinase and endoribonuclease, processes a subset of “tumor suppressor” microRNAs (miRs), leading to their degradation, a pathway we called “IRE1-dependent miRNA Decay”, and therefore contributes to aggressiveness of luminal breast cancer (iScience 2020). Currently, we are investigating whether ER lipid-raft proteins and ER stress sensors act as “cooperating-oncogenes” and as such play important roles in the maintenance of malignancy and therapy-resistance in breast cancer or HCC.