Office Address

 3202 Scott Hall, 540 E Canfield St, Detroit, MI 48201

Department

Center for Molecular Medicine and Genetics 

Laboratory Web Site

https://genetics.wayne.edu/faculty/kezhong-zhang

Research Interests

1. Organelle Stress Response from Endoplasmic Reticulum (ER), Mitochondria, and/or Lysosome.
2. Integrated Stress Response in Inflammation and Metabolism associated with Hyperlipidemia, Fatty Liver Disease, and Type-2 Diabetes.

3. Adverse Health Effects and Mechanistic Basis of Airborne Particulate Matter PM_2.5.

4. Functions and Mechanisms of ER Lipid-raft Proteins and Stress Sensors in Oncogenesis    

Research Description

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.

Recent Publications

 Kim H., Song Z., Zhang R., Davies B.S.J., Zhang K. A Hepatokine Derived from the ER protein CREBH Promotes Triglyceride Metabolism by Stimulating Lipoprotein Lipase Activity. Science Signal. 2023;16:eadd6702.

Kim H, Wei J, Song Z, Mottillo E, Samavati L, Zhang R, Li L, Chen X, Jena BP, Lin JD, Fang D, Zhang K. Regulation of Hepatic Circadian Metabolism by the E3 ubiquitin ligase HRD1-controlled CREBH/PPARα Transcriptional Program. Mol Metabolism 2021;13:49:101192.

Zhang K#, Liu H, Song Z, Jiang Y, Kim H, Samavati L, Nguyen HM, Yang ZQ#. 2020. The UPR Transducer IRE1 Promotes Breast Cancer Malignancy by Degrading Tumor Suppressor microRNAs. iScience. 2020;23:101503.

Wang, J., Qiu, Y., Yang, Z., Kim, H., Qian, Q., Sun, Q., Zhang, C., Yin, L., Fang, D., Back, S., Kaufman, R.J., Yang, L., and Zhang, K. 2018. IRE1α prevents hepatic steatosis by processing and promoting the degradation of select microRNAs. Science Signal 2018;11: pii:eaao4617.

Zhang, K.#, Kim, H., Fu, Z., Qiu, Y., Yang, Z., Wang, J., Zhang, D., Tong, X., Yin, L., Li, J., Wu, J., Qi, N.R., Houten, S.M., Zhang, R.# 2018. Deficiency of the mitochondrial NAD kinase causes stress-induced non-alcoholic steatohepatitis. Gastroenterology 2018;154:224-37.

Education/Training

Shandong University, China B.S. 1992
Shandong University, China M.S. 1995
Fudan University, Shanghai Ph.D. 1998
University of Michigan, Ann Arbor Postdoc 2003

← Return to listing