Professor of Pharmacology
Ph.D., Purdue University
The research in our laboratory mainly focuses on signal transduction in regulating cell growth and organ size. We study the TSC-mTOR and hippo-YAP pathways. Dysregulation of these pathways has been frequently observed in human diseases, particularly cancer. The TSC-mTOR pathway plays a major role in cell size control by promoting biosynthesis and inhibiting autophagy. The Hippo tumor suppressor pathway regulates organ size and tissue homeostasis. Current research includes: 1) mechanisms of mTOR in nutrient signaling and autophagy regulation; 2) regulation of the Hippo pathway by cell-cell contact and G-protein coupled receptor signaling.
BMS Focus Areas:
Zhao, S., Xu, W., et al, Xiong, Y., Guan, K-L., (2010) Regulation of cellular metabolism by protein lysine acetylation. Science 327, 1000-1004.
Kim, J., Kundu, M., Viollet, B., and Guan K-L., (2011) AMPK and mTOR regulate autophagy via direct phosphorylation of ULK1. Nature Cell Biol. 13, 132-141.
Zhao, B., Li, L., Wang, L., Wang, C.Y., Yu, J., and Guan, K-L. (2012) Cell detachment activates the Hippo pathway via cytoskeleton reorganization to induce anoikis and inhibit tumor metastasis. Genes & Dev. 26, 54-68.
Tumaneng, K., Schlegelmilch, K., Russell, R.C., et al., Camargo, F., and Guan, K-L. (2012) YAP mediates crosstalk between the Hippo and PI3K-TOR pathways by suppressing PTEN via miR-29. Nature Cell Biol. 14, 1322-1329.
Yu, F-X., Zhao, B., Panupinthu, N., Jewell, J. L., et al., Mills, G. B., and Guan, K-L. (2012) Regulation of the Hippo-YAP pathway by G-protein coupled receptor signaling. Cell 150, 780-91.
Zhao, D., Zou, S-W., et al., Lei, Q-Y., and Guan, K-L. (2013) Lysine-5 acetylation negatively regulates lactate dehydrogenase A and is decreased in pancreatic cancer. Cancer Cell, 23, 464-476.
Kim, J., Kim, Y.C., Fang, C., Russell, R.C., Kim, J.H., Fan, W., Liu, R., Zhong, Q., and Guan, K-L. (2013) Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell 152, 290-303.
Russell, R.C., Tian, Y., Yuan, H., Park, H.W., Chang, Y.Y., Kim, J., Jim, H., Neufeld, T., Dillin, A., Guan, K-L. (2013) ULK1 induces autophagy by phosphorylating Beclin-1 and activating Vps34 lipid kinase. Nature Cell Biol. (in press).