Kezhong Zhang, PhD
Scott Hall, Rm 3202
540 E. Canfield Avenue
Detroit, MI 48201
Fudan University, PhD, 1998
Research in this laboratory is focused on cellular stress responses originated from the endoplasmic reticulum (ER) and/or mitochondria that modulate inflammation and metabolism that are associated with metabolic disease, autoimmune disease, and cancer. The ER is an organelle that is primarily recognized as a compartment for protein folding and assembly, a pool of intracellular calcium, and a site for lipid and sterol biosynthesis. Physiological states that increase protein-folding demand, or stimuli that disrupt protein folding reactions, create an imbalance between the protein-folding load and capacity of the ER. This can cause accumulation of unfolded or misfolded proteins in the ER lumen -a condition referred to “ER stress”. To ensure the fidelity of protein folding and to handle the accumulation of unfolded or misfolded proteins, the ER has evolved a group of signal transduction pathways collectively termed “Unfolded Protein Response (UPR)” to alter transcriptional and translational programs. The UPR is a critical regulator in the initiation and progression of a variety of human diseases. Research projects in the Zhang laboratory include: 1) regulation of hepatic energy metabolism by ER stress-inducible transcriptional activators; 2) roles and mechanisms for the UPR transducer IRE1a in rheumatoid arthritis and lupus; 3) airborne particulate matter (PM2.5)-induced cellular stress responses and their effects on non-alcoholic steatohepatitis (NASH) and type-2 diabetes; and 4) roles of ER lipid-raft proteins in breast cancer malignancy maintenance and therapy resistance.
Kim H, Mendez R, Zheng Z, Chang L, Cai J, Zhang R, Zhang K. Liver-Enriched Transcription Factor CREBH Interacts With Peroxisome Proliferator-Activated Receptor α to Regulate Metabolic Hormone FGF21. Endocrinology. 2014 Mar;155(3):769-82. doi: 10.1210/en.2013-1490. Epub 2014 Jan 1. PubMed PMID: 24424044; PMCID: PMC3929740.
Zheng Z, Xu X, Zhang X, Wang A, Zhang C, Hüttemann M, Grossman LI, Chen LH, Rajagopalan S, Sun S, Zhang, K. 2013. Exposure to Ambient Particulate Matter Induces a NASH-like Phenotype and Impairs Hepatic Glucose Metabolism in an Animal Model. J. Hepatol. 2013 58: 148-154. PubMed PMID: 22902548; PubMed Central PMCID: PMC3527686
Qiu Q, Zheng Z, Chang L, Zhao YS, Tan C, Dandekar A, Zhang Z, Lin Z, Gui M, Li X, Zhang T, Kong Q, Li H, Chen S, Chen A, Kaufman RJ, Yang WL, Lin HK, Zhang D, Perlman H, Thorp E, Zhang K*, Fang D*. Toll-like receptor-mediated IRE1α activation as a therapeutic target for inflammatory arthritis. EMBO J. 2013 Sep 11;32(18):2477-90. PubMed PMID: 23942232; PMCID: PMC3770952. (* corresponding author).
Zhang C, Wang G, Zheng Z, Maddipati KR, Zhang X, Dyson G, Williams P, Duncan SA, Kaufman RJ, Zhang K. ER-tethered Transcription Factor CREBH Regulates Hepatic Lipogenesis, Fatty Acid Oxidation, and Lipolysis upon Metabolic Stress. Hepatology 2012, 55 (4): 1070-1082. PubMed PMID: 22095841; PMCID: PMC3319338.