George K. Chandy
Physiology & Biophysics, School of Medicine
Phone: (949) 824-6721
Email: gchandy@uci.edu
http://www.faculty.uci.edu/profile.cfm?faculty_id=2178
George Chandy
Recently, Dr. Chandy and colleagues discovered an ShK-like domain in MMP23. The MMP23-ShK domain blocks Kv1.3 potassium channels in T cells and suppresses the proliferation of these cells. MMP23 is over-expressed in prostatic tumor tissue and correlates with pre-operative PSA titers, and it also appears to correlate strongly with the relapse rate. Dr. Chandy hypothesizes that the ShK-domain in MMP23 suppresses T cells that infiltrate the tumor by blocking the Kv1.3 channel. Studies are underway to test this idea.
Selected Publications:
Vennekamp, J., Wulff, H., Beeton, C., Calabresi, P. A., Grissmer, S., Hansel, W., and Chandy, K. G. (2004). Kv1.3-blocking 5-phenylalkoxypsoralens: a new class of immunomodulators. Mol Pharmacol 65(6), 1364-74.
Wulff, H., Knaus, H. G., Pennington, M., and Chandy, K. G. (2004). K+ channel expression during B cell differentiation: implications for immunomodulation and autoimmunity. J Immunol 173(2), 776-86.
Beeton, C., Pennington, M. W., Wulff, H., Singh, S., Nugent, D., Crossley, G., Khaytin, I., Calabresi, P. A., Chen, C. Y., Gutman, G. A., and Chandy, K. G. (2005). Targeting effector memory T cells with a selective peptide inhibitor of Kv1.3 channels for therapy of autoimmune diseases. Mol Pharmacol 67(4), 1369-81.
Rus, H., Pardo, C. A., Hu, L., Darrah, E., Cudrici, C., Niculescu, T., Niculescu, F., Mullen, K. M., Allie, R., Guo, L., Wulff, H., Beeton, C., Judge, S. I., Kerr, D. A., Knaus, H. G., Chandy, K. G., and Calabresi, P. A. (2005). The voltage-gated potassium channel Kv1.3 is highly expressed on inflammatory infiltrates in multiple sclerosis brain. Proc Natl Acad Sci U S A 102(31), 11094-9.
Beeton, C., Wulff, H., Standifer, N. E., Azam, P., Mullen, K. M., Pennington, M. W., Kolski-Andreaco, A., Wei, E., Grino, A., Counts, D. R., Wang, P. H., LeeHealey, C. J., B, S. A., Sankaranarayanan, A., Homerick, D., Roeck, W. W., Tehranzadeh, J., Stanhope, K. L., Zimin, P., Havel, P. J., Griffey, S., Knaus, H. G., Nepom, G. T., Gutman, G. A., Calabresi, P. A., and Chandy, K. G. (2006). Kv1.3 channels are a therapeutic target for T cell-mediated autoimmune diseases. Proc Natl Acad Sci U S A 103(46), 17414-9.
Beeton, C., Smith, B. J., Sabo, J. K., Crossley, G., Nugent, D., Khaytin, I., Chi, V., Chandy, K. G., Pennington, M. W., and Norton, R. S. (2008). The D-diastereomer of ShK toxin selectively blocks voltage-gated K+ channels and inhibits T lymphocyte proliferation. J Biol Chem 283(2), 988-97. |
