Assistant 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 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.
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.
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.
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