George K. ChandyProfessor, Physiology & Biophysics |
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Research Interests |
Role of potassium channels in lymphocyte function and disease | |
| URL | www.ucihs.uci.edu/pandb/faculty/kgcres.html | |
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Research Abstract |
We are developing therapeutic agents for human disease by targeting potassium channels. We focus on autoimmune diseases (multiple sclerosis, rheumatoid arthritis, type-1 diabetes mellitus, psoriasis), organ and bone marrow transplantation, atherosclerosis, vascular restenosis following angioplasty, and neurological diseases. We have cloned the relevant potassium channel genes, developed specific inhibitors of these channels, demonstrated the functional role of the channels in normal and diseased cells, and demonstrated therapeutic efficacy of our inhibitors in animal models of human disease. Pre-clinical toxicity studies are underway for the most promising compounds. We intend to evaluate these compounds in patients in the next few years with the hope that someday we will ameliorate human disease. | |
| Publications | DeCoursey T.E., Chandy K.G., Gupta, S. Cahalan, M. (1984) Voltage gated potassium channels in human T lymphocytes: a role in mitogenesis? Nature 307, 465. | |
| Chandy K.G., DeCoursey T.E., Cahalan M.D., McLaughlin C., Gupta S. (1984) Voltage-gated potassium channels are required for human T cell activation. J. Exp. Med. 160, 369. | ||
| Chandy K.G., DeCoursey T.E., Fischbach M., Talal, N., Cahalan M.D., Gupta S. (1986) Altered K+ channel expression in abnormal T lymphocytes from mice with the lpr gene mutation. Science 233, 1197. | ||
| Chandy, K. G., Williams, C., Spencer, R. H., Aguilar, B. A., Ghanshani, S., Tempel, B., Gutman, G. A. (1990) A family of three mouse K+ channel genes with intronless coding regions. Science 247, 973. | ||
| Grissmer, S., Dethlefs, B., Wasmuth, J., Gutman, G., Goldin, A. L., Cahalan, M. D., Chandy, K. G. (1990) Expression and chromosomal localization of a lymphocyte K+ channel. Proc. Natl. Acad. Sci. USA 87, 9411 | ||
| Aiyar, J., Withka, J., Rizzi, J., Dethlefs, B., Simon, M., Chao-lin Lee, Boyd, J., Hall, J., Gutman, G.A., Chandy K. G. (1995). Topological map of the external vestibule at the external entrance to the pore. Neuron 15, 1169. | ||
| Fanger, C. S. Ghanshani, N. J. Logsdon,H. Rauer, K. Kalman, J. Zhou, K. Beckingham, Chandy, KG, Cahalan, MD, Aiyar, J. (1999) Calmodulin mediates Calcium-Dependent Activation of the Intermediate Conductance KCa Channel, IKCa1. J. Biol. Chem 274:5746-5754 | ||
| K Kalman, M. Pennington, M. D. Lanigan, A. Nguyen, Kem, R., Grissmer, S., K. Paschetto, S. Stetz, G. A. Gutman,, E. Christian+, M. D. Cahalan, R. S. Norton, Chandy, K. G. (1998) ShK-Dap22: A potent Kv1.3-specific immunosuppressive peptide. J. Biol. Chem. 273:32697-707. | ||
| Wulff, H., Miller, M., Grissmer, S., Hansel, W., Cahalan, M.D., Chandy, KG. (2000) Design of a selective inhibitor of the intermediate-conductance calcium-activated K+ channel, IKCa1: a potential immunosuppressant. Proc. Natl. Acad. Sci. USA. 97:8151-6 | ||
| Beeton, C., Wulff, H., Barbaria, J., Clot-Faybesse, O., Pennington, M., Bernard, D., Cahalan, M.D., Chandy, KG. and Béraud, E. Selective blockade of T lymphocyte K+ channels ameliorates experimental autoimmune encephalomyelitis, a model for multiple sclerosis. (2001) Proc. Natl. Acad. Sci. USA. 98: 13942-13947 | ||
| Wulff, H., Calabresi, P., Beeton, C., Yun, S., Allie, R., Pennington, M., Chandy, K.G. (2003). The voltage-gated Kv1.3 K+ channel in effector memory T cells as new target for MS. J. Clinical Investigation. 111, 1703-1713 | ||
| Chandy, K. G, Wulff, H., Beeton, C., Pennington, M., Gutman, G. A., Cahalan, M. D. (2004). Potassium channels as targets for specific immunomodulation. Trends in Pharmacological Sciences 25, 280-289 | ||
| Wulff, H., Knaus, H-G, Pennington, M., Chandy, K. G. (2004). K+ channel expression during B-cell differentiation: implications for immunomodulation and autoimmune disorders. J. Immunol. 173:776-786. | ||
| Beeton, C., Pennington, M. W., Singh, S., Nugent, D., Crossley, G., Khaytin, I., Calabresi, P. A., Chandy, K. G. (2005). Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases. Molecular Pharmacology 67:1369-1381. | ||
| Rus, H, Pardo CA, Hu L, Darrah E, Cudrici C, Niculescu T, Niculescu F, Mullen KM,, Allie R, Guo L, Wulff H, Beeton C, Judge SIV, Kerr DA, Knaus H-G, Chandy KG, and Calabresi PA (2005). The Voltage-Gated Potassium Channel Kv1.3 is Highly Expressed on Inflammatory Infiltrates in Multiple Sclerosis Brain. Proc. Natl. Acad. Sci. USA 102: 11094-11099 | ||
| Shakkottai, V.G, Chou, C-h, Oddo, S, Sailer, C.A., Knaus, H-G, Gutman, G.A., Barish, M.E, LaFerla, F.M., Chandy, K.G. (2004). Enhanced neuronal excitability in the absence of neurodegeneration induces cerebellar ataxia. J. Clinical Investigation 113, 582-590. (also see “Commentary” in same issue of J. Clin. Invest, and the “Highlight” in Nature Reviews Neuroscience). | ||
| Kohler R, Wulff H, Eichler I, Kneifel M, Neumann D, Knorr A, Grgic I, Kampfe D, Si H, Wibawa J, Real R, Borner K, Brakemeier S, Orzechowski HD, Reusch HP, Paul M, Chandy KG, Hoyer J. (2003) Blockade of the intermediate-conductance calcium-activated potassium channel as a new therapeutic strategy for restenosis. Circulation 108, 1119-25 | ||
| Graduate Programs |
Structural Biology and Molecular Biophysics |
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| Link to this profile | http://www.faculty.uci.edu/profile.cfm?faculty_id=2178 | |
| Last updated | 08/06/2008 | |