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 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

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.

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.

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

Krebsbach, P., Zhang, K., Malik, A., Kurachi, K. 2003. Bone marrow stromal cells as a Genetic platform for systemic delivery of therapeutic proteins in vivo: human factor IX model. Journal of Gene Medicine 5(1): 11-7

Zhang, K., Kurachi, S., Kurachi, K. 2002. New function for age-related stability element in conferring strict tissue-specific expression of human factor IX and protein C genes. Thrombosis and Haemostasis 88: 537-539

Zhang, K., Kurachi, S., Kurachi, K. 2002. Genetic mechanisms of age regulation of protein C and blood coagulation. Journal of Biological Chemistry, 277 (6): 4532-4540

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