Our current research interests focus on WNK kinases and the anti-aging hormone,Klotho. WNKs are novel protein kinases with a unique kinase domain. Mutations of two members, WNK1 and WNK4, cause hypertension and hyperkalemia in humans. We study the role and mechanism of WNK1 in the regulation of cardiovascular development and of WNK1 and WNK4 in the regulation of activity of ion channels. These actions of WNKs lead to development of hypertension and hyperkalemia in humans. Klotho is a mammalian senescence suppression protein. Klotho-deficient mice exhibit premature aging and imbalance of ion homeostasis. The target(s) for Klotho in not known. We aim to uncover the biological roles of Klotho and the mechanism of regulation.
RESEARCH INTERESTS
Ion channels and human diseases caused by dysregulation of ion channels, including hypertension, polycystic kidney disease, kidney stone disease, and genetic diseases of K+ and Mg2+ disorders
RECENT PUBLICATIONS
Xu, B-e., Stippec, S., Chu, P-Y., Lazrak, A., Li, X.-J., Lee, B.-H., English, J. M., Ortega, B., Huang, C.-L.*, and Cobb, M. H.* (*co-corresponding authors), "WNK1 activates SGK1 to regulate the epithelial sodium channel." Proc. Natl. Acad. Sci., 102:10315-10320, July 2005
Yeh, B.-I.., Kim, Y. K., Jabbar, W., and Huang, C.-L, "Conformational changes of pore helix coupled to gating of TRPV5 by protons" EMBO Journal, 24:3224-3234, September 2005
Lee, J., Cha, S.-K., Sun, T.-J., and Huang, C.-L., "PIP2 activates TRPV5 and releases its inhibition by intracellular Mg2+" J Gen Physiol, 126:439-451, November 2005
Lazrak, A., Liu, Z., and Huang, C.-L, "Antagonistic regulation of ROMK by long and kidney-specific WNK1 isoforms" Proc Natl Acad Sci, 103:1615-1620, January 2006
Guocheng He, Hao-Ran Wang, Shao-Kuei Huang, Chou-long Huang, "Intersectin links WNK kinases to endocytosis of ROMK" Journal of Clinical Investigation, 117:1078-1087, 2007
SIGNIFICANT PUBLICATIONS
Huang C.-L., Slesinger, P.A., Casey, P.J., Jan, Y.N. and Jan, L.Y., "Evidence that direct binding of G beta gamma to the GIRK1 G protein-gated inwardly rectifying K+ channel is important for channel activation" Neuron, 15:1133-1143, November 1995
Huang, C.-L., Feng, S. and Hilgemann, D.W., "Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gbg." Nature, 391:803-806, February 1998
Liou, H.-H., Zhou, S.S., and Huang C.-L.., "Phosphorylation of ROMK1 channel by PKA regulates channel activity via a PIP2-dependent mechanism." Proc Natl Acad Sci, 96:5820-5825, May 1999
Huang, C-L, "The TRP superfamily of ion channels" J Am Soc Nephrol, 15:1690-1699, 2004
Xie J, Craig L, Cobb MH, Huang C-L, "Role of with-no-lysine [K] kinases in the pathogenesis of Gordon’s syndrome" Pediatr Nephrol, Epub 2006
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