Michael D. Cahalan
Physiology & Biophysics
School of Medicine
Phone: (949) 824-7776
Email: mcahalan@uci.edu
http://crt.biomol.uci.edu/
http://www.faculty.uci.edu/profile.cfm?faculty_id=2150
Michael Cahalan
Dr. Cahalan pioneered the study of ion channels and their function in the immune system. He discovered several novel ion channels in T lymphocytes and identified the molecules that form them. A voltage-gated potassium channel first described by his group shows great promise as a therapeutic target for treatment of autoimmune disorders, with proven efficacy in animal models. Calcium is a vital second messenger in lymphocytes. Dr. Cahalan’s work provided the electrophysiological signature of calcium entry triggered by antigen. His single-cell imaging experiments decoded the intracellular Ca 2+ signaling requirements for gene transcriptional activation and cell motility in lymphocytes. Of particular note, using an RNAi screening approach he identified two proteins, STIM and Orai, that together form the molecular basis for store-operated calcium channel activity. By mutational analysis, Dr. Cahalan showed that STIM is a dual-function molecule, serving as the Ca 2+ sensor in the endoplasmic reticulum and as the messenger that relays information to the plasma membrane. The laboratory carried out a critical genome-wide RNAi screen that led to the co-discovery of the Ca 2+ channel-forming protein Orai. His recent work provides the clincher to the story, proving that Orai embodies the pore of the calcium channel. In addition to extensive investigation of ion channels and calcium signaling in lymphocytes, he pioneered the use of two-photon microscopy to image cell motility and interaction dynamics inside lymphoid organs. In combination with targeted gene deletion and specific pharmacological agents, live-cell i mmuno-imaging is continuing to reveal important insights into the choreography of immune responses in vivo .
Selected Publications:
Miller, M. J., Wei, S. H., Parker, I., and Cahalan, M. D. (2002). Two-photon imaging of lymphocyte motility and antigen response in intact lymph node. Science 296(5574), 1869-73.
Miller, M. J., Wei, S. H., Cahalan, M. D., and Parker, I. (2003). Autonomous T cell trafficking examined in vivo with intravital two-photon microscopy. Proc Natl Acad Sci U S A 100(5), 2604-9.
Zhang, S. L., Yu, Y., Roos, J., Kozak, J. A., Deerinck, T. J., Ellisman, M. H., Stauderman, K. A., and Cahalan, M. D. (2005). STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature 437(7060), 902-5.
Yeromin, A. V., Zhang, S. L., Jiang, W., Yu, Y., Safrina, O., and Cahalan, M. D. (2006). Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai. Nature 443(7108), 226-9.
Zhang, S. L., Yeromin, A. V., Zhang, X. H., Yu, Y., Safrina, O., Penna, A., Roos, J., Stauderman, K. A., and Cahalan, M. D. (2006). Genome-wide RNAi screen of Ca(2+) influx identifies genes that regulate Ca(2+) release-activated Ca(2+) channel activity. Proc Natl Acad Sci U S A 103(24), 9357-62. |
