Kezhong Zhang, Ph.D.
Associate Professor


3202 Scott Hall
540 East Canfield
Detroit, MI 48201
Voice: 313-577-2669
FAX: 313-577-5326
kzhang@med.wayne.edu
zhanglaboratory.wayne.edu

 

Associate Professor (also with Immunology and Microbiology); Ph.D., Fudan (China), 1998. Signaling pathways from the endoplasmic reticulum and mitochondria; unfolded protein response, oxidative stress and inflammation in health and disease.

Research Interests

Research in this laboratory is focused on stress signaling and the inflammatory response originated from the ER and mitochondria that modulate cell metabolism and disease pathogenesis. Biochemical, physiological or pathological stimuli, such as viral infection, chemical insult, genetic mutation, metabolic syndromes, nutrient deprivation and even normal differentiation of specialized cells, can disrupt ER homeostasis and subsequently cause accumulation of unfolded or misfolded proteins in the ER lumen-a condition referred to as “ER stress”. Under those conditions, the ER and mitochondria can interact with each other and build up a dynamic network where they generate calcium signal, oxidative stress and the inflammatory response. We use biochemical approaches and animal genetics to investigate how cellular stress activates stress sensor molecules including protein kinase PERK, kinase/endoribonuclease IRE1 and bZIP transcription factors CREBH and ATF6 to induce inflammation that initiates and/or propagates diseases, particularly atherosclerosis and neurodegenerative disease. In addition, we also work on the involvement of intracellular stress signaling in lymphocyte differentiation and function.


Selected Publications

Mendez, R. Zheng, Z., Fan, Z., Rajagopalan, S., Sun, Q., Zhang, K. 2013. Exposure to fine airborne particulate matter includes macrophage infiltration, unfolded protein response, and lipid deposition in white adipose tissue.  AM J Transl Res. 5(2):224-234.

Lee, J.S., Hou, X., Bishop, N., Wang, S., Flack, A., Chow, W.J., Chen, X., Mao, G., Taatjes, D.J., Sun, F., Zhang, K., Jena, B.P. 2013. Aquaporin-assisted and ER-mediated mitochondrial fission: A hypothesis. Micron 47:50-58

Zheng, Z., Xu, X., Zhang, X., Wang, A., Zhang, C., Hüttemann, M., Grossman, L.I., Chen, L-H, Rajagopalan, S., Sun, S., and Zhang, K. 2013.  Exposure to Ambient Particulate Matter Induces a Nash-like Phenotype and Impairs Hepatic Glucose Metabolishm in an Animal Model. Journal of Hepatology 58: 148 - 154

Wang, G., Liu, G., Wang, X., Sethi, X., Rouba, A.F., Abrams, J., Zheng, Z., Zhang, K., Eithier, X., and Yang, Z.Q. 2012. Endoplasmic reticulum factor ERLIN2 plays an oncogenic role by modulating ER stress response in breast cancer.  BMC Cancer 2012, 12:225

Wang, G., Zhang, X., Lee, J-S., Wang, X., Yang, Z., and Zhang, K. 2012.  Endoplasmic Reticulum Factor ERLIN2 Regulates Cytosolic Lipid Contents in Human Breast Cancer Cells.  Biochem. J 446: 415-425.

Lee, J-S., Zheng, Z., Mendez, R., Ha, S-W., Xie, Y., and Zhang, K. 2012.  Pharmacologic ER Stress Induces Non-alcoholic Steatohepatitis in an Animal Model.  Toxicology Letters 211(1): 29-39

Lee, J.S., Mendez, R., Heng, H., Yang, Z., and Zang, K. 2012 Pharmacological ER stress promotes hepatic lipogenesis and lipid droplet formation.  AM J Transl Res 4(1): 102-113

Zhang, C., Wang, G., Zheng, Z., MAddipati, K.R., Zhang, X., Dyson, G., Williams, P., Duncan, S.A., Kaufman, R.J., and Zhang, K. 2012. ER-tethered Transcription Factor CREBH Regulates Hepatic Lipogenesis, Fatty Acid Oxidation, and Lipolysis upon Metabolic Stress.  Hepatology 55(4): 1070-1082.

Zhang, k., Wang, s., Malhotra, j., Hassler, J.R., Back, S.H., Wang, G., Chang, L., Xu, W., Miao, H., Leonardi, R., Chen, E.Y., Jackowski, S., and Kaufman, R.J. 2011.  The Unfolded Protein Response Transducer IRE1a Prevents ER Stress-Induced Hepatic Steatosis.  EMBO J 30: 1357-1375

Zheng, Z., Zhang, C., Zhang, K. 2011. Measurement of ER Stress Response and Inflammation in the Mouse Model of Non-alcoholic Fatty Liver Disease. Methods in Enzymology 489: 329-348

Laing, S., Wang, G., Briazova, T., Zhang, C., Wang, A., Zheng, Z., Gow, A., Chen, A.F., Rajagopalan, S., Chen, L.C., Sun, Q., Zhang, K. 2010. Airborne particulate matter selectively activates endoplasmic reticulum stress response in the lung and liver tissues. Am J Physiol Cell Physiol. 299(4):C736-749.

Wang, G., Yang, Z.Q., Zhang, K. 2010. Endoplasmic reticulum stress response in cancer: molecular mechanism and therapeutic potential. Am J Transl Res. 2(1):65-674.

Vecchi, C., Montosi, G., Zhang, K., Lamberti, I., Duncan, S.A., Kaufman, R.J., Pietrangelo, A. 2009. ER stress controls iron metabolism through induction of hepcidin. Science. 325(5942):877-880.

Kurachi, S., Huo, J., Ameri, A., Zhang, K., Yoshizawa, A., Kurachi, K. 2009. An Age Related Homeostasis Mechanism is Essential for Spontaneous Amelioration of Hemophilia B Leyden. Proc Natl Acad Sci USA 106 (19):7921-7926.

Luebke-Wheeler J, Zhang K, Battle M, Si-Tayeb K, Garrison W, Chhinder S, Li J, Kaufman RJ, Duncan SA. 2008. Hepatocyte nuclear factor 4α is implicated in endoplasmic reticulum stress-induced acute phase response by regulating expression of CREB-H. Hepatology 48(4):1242-1250

Malhotra, J.D., Miao, H., Zhang, K., Wolfson, A., Pennathur, S., Pipe, S.W., Kaufman, R.J. 2008. Antioxidants reduce endoplasmic reticulum stress and improve protein secretion. Proc Natl Acad Sci USA 105 (47):18525-18530.

Zhang, K., Kaufman, R.J. 2008. Identification and Characterization of Endoplasmic Reticulum Stress-induced Apoptosis in vivo. Methods in Enzymology 442:395-419.

Zhang, K., Kaufman, R.J. 2008. From endoplasmic-reticulum stress to the inflammatory response. Nature 454(7203):455-462.

Zhang, K., Shen, X., Wu, J., Sakaki, K., Saunders, T., Rutkowski, D.T., Back, S.H., Kaufman, R.J. 2006. Endoplasmic Reticulum Stress Activates Cleavage of CREBH to Induce a Systemic Inflammatory Response. Cell 124: 587-599.

Zhang, K., Kaufman, R.J. 2006. The unfolded Protein Response: an ER Stress Signaling Critical for Health and Diseases. Neurology 66: S102-109.

Zhang, K., Wong, H.N., Song, B., Miller, C.N., Scheuner, D., Kaufman, R.J. 2005. The unfolded protein response sensor IRE1α is required at 2 distinct steps in B cell lymphopoiesis. Journal of Clinical Investigation. 115 (3): 268-281.

Back, S.H., Schroder, M., Lee, K., Zhang, K., Kaufman, R.J. 2005. ER stress signaling by regulated splicing: IRE1/HAC1/XBP1. Methods 35(4): 395-416

Hsu, L.H., Park, J.M., Zhang, K., Luo, J.L., Maeda, S., Kaufman, R.J., Eckmann, L., Guiney, D.G., Karin, M. 2004. The protein kinase PKR is required for macrophage apoptosis after activation of Toll-like receptor 4. Nature 428 (6980): 341-345.

Zhang, K., Kaufman, R.J. 2004. Signaling the unfolded protein response from the endoplasmic reticulum. Journal of Biological Chemistry 279 (25): 25935-25938

Zhang, K., Kaufman, R.J. 2003. Unfolding the toxicity of cholesterol. Nature Cell Biology 5 (9): 769-770

Zhang, K., Kurachi, S., Kurachi, K. 2003. Limitation in use of heterologous reporter genes for gene promoter analysis: silencer activity associated with the chloramphenicol acetyltransferase reporter gene. Journal of Biological Chemistry 278 (7): 4826-4830



 
 
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