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Michael D. Cahalan

Professor and Chair, Physiology & Biophysics
School of Medicine

Ph.D., University of Washington

Phone: (949) 824-7776
Fax: (949) 824-3143
Email: mcahalan@uci.edu

University of California, Irvine
Department of Physiology and Biophysics
285 Irvine Hall
Mail Code: 4561
Irvine, CA 92697

picture of Michael D. Cahalan

Research
Interests
Ion Channels, Calcium Signaling, T Lymphocytes, Imaging, Cell Motility and Interaction Dynamics
   
URL Cahalan Lab
   
Academic
Distinctions
Graduated Oberlin College Phi Beta Kappa, Magna cum laude, 1970
Muscular Dystrophy Association Postdoctoral Fellowship, 1976
NIH Research Career Development Award, 1981
Alexander von Humboldt Senior Scientist Prize, 1990
Department Chair 1991-1995, 2005-present
Athalie Clark Research Achievement Award, 1997
President, Society of General Physiologists, 1998
Kenneth S. Cole Award in Membrane Biophysics, 2000
Javits Neuroscience Investigator Award, 2006
Henry Kunkel Society, elected 2008
Excellence in Teaching Award from medical students, 2009
Elected to the U.S. National Academy of Sciences, 2010
UCI Distinguished Faculty Award for Research, 2011
   
Appointments postdoctoral research with Clay Armstrong, University of Pennsylvania, 1974-1977
   
Research
Abstract
Cahalan’s pioneering work identified the pivotal role of ion channels in the immune response. He elucidated the physiological functions and the molecular basis for calcium signaling that activates T lymphocytes. By imaging in lymphoid organs, his work has also revealed an elegant cellular choreography that underlies the initiation of the immune response in vivo.

• Ion Channels in the Immune System. Cahalan’s group discovered the biophysical phenotype and molecular properties of ion channel types in T lymphocytes. His work shows that ion channel types play vital roles in T cell activation, cell motility, and cell volume regulation. A voltage-gated potassium channel (Kv1.3) shows great promise as a therapeutic target for treatment of inflammatory and autoimmune disorders, with proven efficacy in animal models of multiple sclerosis, rheumatoid arthritis and delayed type hypersensitivity. Calcium is a vital second messenger in lymphocytes. Cahalan’s work provided the electrophysiological signature of calcium entry triggered by antigen. His single-cell imaging experiments decoded the intracellular calcium 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, Cahalan showed that STIM functions as the Ca2+ sensor in the endoplasmic reticulum, as the messenger to the plasma membrane, and as the effector molecule that activates Ca2+ influx. The Cahalan group carried out a critical genome-wide RNAi screen that led to the co-discovery of the Ca2+ channel-forming protein Orai. His recent work proved that Orai embodies the pore of the calcium channel. These discoveries were noted by Science magazine as “Cell Signaling Breakthroughs of the Year” in 2005 and 2006.

• Immunoimaging. Cahalan’s group, together with Ian Parker, pioneered the use of two-photon microscopy to image cell motility and interaction dynamics inside lymphoid organs. T and B cells are highly motile in their native habitat and this plays an important role in locating and responding to antigen. During the initiation of an immune response, T cells interact with and respond to dendritic cells, forming clusters; whereas individual T cells pair up with individual B cells while delivering “help” to trigger antibody production. In vivo imaging approaches, in combination with targeted gene deletion and specific pharmacological agents, are continuing to revealing important insights into the choreography of immune responses in vivo.
   
Publications Flach, H., M. Rosenbaum, M. Duchniewicz, S. Kim, S.L. Zhang, M.D. Cahalan, G. Mittler, and R. Grosschedl. 2010. Mzb1 protein regulates calcium homeostasis, antibody secretion, and integrin activation innate-like B cells. Immunity 33: 723-735. PMID: 21093319.
   
  Cahalan, M.D. 2010. How to STIMulate calcium channels. Science 330: 43-44. PMID: 20929798.
   
  Krummel, M.F. and M.D. Cahalan. 2010. The immunological synapse: a dynamic platform for local signaling. Journal of Clinical Immunology 30: 364-372. PMID: 20390326.
   
  Sen, D., L. Forrest, T.B. Kepler, I. Parker, M.D. Cahalan. 2010. Selective and site-specific mobilization of dermal dendritic cells and Langerhans cells by Th1- and Th2-polarizing adjuvants. Proceedings of the National Academy of Sciences U.S.A 107: 8334-9.
   
  Garrod, K.R., F-C. Liu, L.E. Forrest, I. Parker, S-M. Kang, and M.D. Cahalan. 2010. Natural killer cell patrolling and elimination of donor-derived dendritic cells favors indirect alloreactivity. Journal of Immunology 184: 2329-2336.
   
  Garrod, K.R. and M.D. Cahalan. Illuminating intranodal natural killer cell behaviour using two-photon microscopy. In Natural Killer Cells, first edition. Michael Lotze and Angus Thomson, eds. Elsevier, 2009.
   
  Penna, A., S.L. Zhang, A.V. Yeromin, and M.D. Cahalan. 2009. “Molecular Mechanism of Store-Operated Ca2+ Signaling and CRAC Channel Activation Mediated by STIM and Orai”. In Ralph A. Bradshaw and Edward A. Dennis, editors: Handbook of Cell Signaling 2nd edition, Oxford:Academic Press, 2009, pp. 209-216.
   
  Cahalan, M.D. 2009. STIM-ulating store-operated Ca2+ entry. Nature Cell Biology 11: 669-677.
   
  Sen, D., T.J. Deerinck, M.H. Ellisman, I. Parker, and M.D. Cahalan. 2008. Quantum dots for tracking dendritic cells and priming an immune response in vitro and in vivo. PLoS ONE ep 29;3(9):e3290.
   
  Penna, A., A. Demuro, A.V. Yeromin, S.L. Zhang, O. Safrina, I. Parker, and M.D. Cahalan. 2008. The CRAC channel consists of a tetramer formed by Stim-induced dimerization of Orai dimers. Nature 456: 116-120.
   
  Matheu, M.P., C. Beeton, A. Garcia, V. Chi, K. Monaghan, M.I. Uemura, D. Li, S. Pal, L.M. de la Maza, E. Monuki, A. Flugel, M.W. Pennington, I. Parker, K.G. Chandy, and M.D. Cahalan. 2008. In situ imaging of effector/memory T cells during DTH and suppression by Kv1.3 channel block. Immunity 29: 602-614.
   
  Zhang, S.L., J.A. Kozak, W.Jiang, A.V. Yeromin, J. Chen, Y. Yu, A. Penna, W. Shen, V. Chi, and M.D. Cahalan. 2008. Store-dependent and -independent modes regulating Ca2+ release-activated Ca2+ channel activity of human Orai1 and Orai3. Journal of Biological Chemistry 283: 17662-17671.
   
  Lioudyno, M.I., J.A. Kozak. A. Penna, O. Safrina, S.L. Zhang, D. Sen, J. Roos, K.A. Stauderman, and M.D. Cahalan. 2008. Orai1 and STIM1 move to the immunological synapse and are up-regulated during T cell activation. Proceedings of the National Academy of Sciences U.S.A. 105:2011-2016.
   
  Cahalan, M.D. and I. Parker. 2008. Choreography of cell motility and interaction dynamics imaged by two-photon microscopy in lymphoid organs. Annual Review of Immunology 26: 585-626.
   
  Matheu, M.P., J.A. Deane, I. Parker, D.A. Fruman, and M.D. Cahalan. 2007 Class IA phosphoinositide 3-kinase modulates basal lymphocyte motility in the lymph node. Journal of Immunology 179: 2261-2269.
   
  Garrod, K.R., S.H. Wei, I. Parker, and M.D. Cahalan. 2007. Natural killer cells actively patrol peripheral lymph nodes forming stable conjugates to eliminate MHC-mismatched targets. Proceedings of the National Academy of Sciences U.S.A. 104: 12081-12086.
   
  Wei, S.H., O. Safrina, Y. Yu, K.R. Garrod, M.D. Cahalan, and I. Parker. 2007 Ca2+ signals in CD4+ T cells during early contacts with antigen-bearing dendritic cells in lymph node. Journal of Immunology 179: 1586-1594.
   
  Cahalan, M.D., S.L. Zhang, A.V. Yeromin, K. Ohlsen, J. Roos, and K.A. Stauderman. 2007. Molecular basis of the CRAC channel. Cell Calcium 42:133-144.
   
  Yeromin, A.V., S.L. Zhang, W. Jiang, Y. Yu, O. Safrina, and M.D. Cahalan. 2006. Molecular identification of the CRAC channel by altered ion selectivity in a mutant of Orai. Nature 443:226-229.
   
  Sanna, M.G., S.K. Wang, P.J. Gonzalez-Cabrera, A. Don, D. Marsolais, M.P. Matheu, S.H. Wei, I. Parker, E. Jo, W.C. Cheng, M.D. Cahalan, C.H. Wong, H. Rosen. 2006. Enhancement of capillary leakage and restoration of lymphocyte egress by a chiral S1P(1) antagonist in vivo. Nature Chemical Biology 2:434-441.
   
  Zhang S.L., A.V. Yeromin, X.H-F. Zhang, Y. Yu, O. Safrina, A. Penna, J. Roos, K.A. Stauderman, and M.D. Cahalan. 2006. A genome-wide RNAi screen of Ca2+ influx identifies genes that regulate CRAC channel activity. Proceedings of the National Academy of Sciences U.S.A.103: 9357-9362.
   
  Cahalan, M.D. and G.A. Gutman. 2006. The sense of place in the immune system. Nature Immunology 7: 329-332.
   
  Cahalan, M.D. and I. Parker. 2006. Imaging the choreography of lymphocyte trafficking and the immune response. Current Opinion in Immunology 18:476-482.
   
  Cahalan, M.D. and I. Parker. 2005. Close encounters of the first and second kind: T–DC and T–B interactions in the lymph node. Seminars in Immunology 17: 442–451.
   
  Wei, S.H., H. Rosen, M.P. Matheu, M.G. Sanna, S-K. Wang, E. Jo, C-H Wong, I. Parker, and M.D. Cahalan. 2005. S1P1 receptor agonism inhibits transendothelial migration of medullary T cells to lymphatic sinuses. Nature Immunology 6, 1228 - 1235.
   
  Newton, R.H., S. Leverrier, S. Srikanth, Y. Gwack, M.D. Cahalan, and C.M. Walsh. 2011. Protein kinase D orchestrates the activation of DRAK2 in response to TCR-induced Ca2+ influx and mitochondrial reactive oxygen generation. Journal of Immunology 186:940-50. PMID: 21148796.
   
  Cahalan, M.D. and K.G. Chandy. 2009. The functional network of ion channels in T lymphocytes. Immunological Reviews, 231: 59-87.
   
  Kozak, J.A., M. Matsushita, A.C. Nairn, and M.D. Cahalan. 2005. Charge screening by internal pH and polyvalent cations as a mechanism for activation, inhibition and rundown of TRPM7/MIC channels. Journal of General Physiology 126:499-514.
   
  Zhang S.L. Y. Yu, J. Roos, J.A. Kozak, T.J. Deerinck, M.H. Ellisman, K.A. Stauderman, and M.D. Cahalan. 2005. STIM1 is a Ca2+ sensor that activates CRAC channels and migrates from the Ca2+ store to the plasma membrane. Nature 437:902-905.
   
  Okada, T., M.J. Miller, I. Parker, M.F. Krummel, M. Neighbors, S.B. Hartley, A. O’Garra, M.D. Cahalan, and J.G. Cyster. 2005. Antigen-engaged B cells undergo chemotaxis toward the T zone and form motile conjugates with helper T cells. PLoS, Biology 3:1047-061.
   
  Zinselmeyer, B.H., Dempster, J., Gurney, A.M., Wokosin, D., Miller, M.J., Ho, H., Millington, O.R., Smith, K.M., Rush, C.M., Parker, I., Cahalan, M.D., Brewer, J.M., Garside, P. 2005. In situ characterisation of CD4+ T cell behaviour in lymphoid tissues during the induction of oral priming and tolerance. Journal of Experimental Medicine 201:1815-1823.
   
  Roos, J. DiGregorio, P.J., A.V. Yeromin, K. Ohlsen, M. Lioudyno, S. Zhang, O. Safrina, J.A. Kozak, S. Wagner, M.D. Cahalan, G. Velicelebi, and K.A. Stauderman. 2005. STIM1, an essential and conserved component of store-operated calcium channel function. Journal of Cell Biology 169:435-445.
   
  Matsushita, M., J.A. Kozak, Y. Shimizu, D. McLachlin, H. Yamaguchi, F.Y Wei, K. Tomizawa, H. Matsui, B. Chait, M.D. Cahalan, A.C. Nairn. 2005. Channel function is dissociated from the intrinsic kinase activity and autophosphorylation of TRPM7/CHAK1. Journal of Biological Chemistry 280:20793-803.
   
  Miller, M.J., A. Safrina, I. Parker, and M.D. Cahalan. 2004. Imaging the single-cell dynamics of CD4+ T cell activation by dendritic cells in lymph nodes. Journal of Experimental Medicine 200:847-856.
   
  Chandy, K.G., H. Wulff, C. Beeton, M. Pennington, G.A. Gutman, M.D. Cahalan. 2004. Potassium channels as targets for specific immunosuppression. Trends in Pharmacological Sciences 25:280-289.
   
  Yeromin A.V., J. Roos, K.A. Stauderman, and M.D. Cahalan. 2004. A store-operated calcium channel in Drosophila S2 cells. Journal of General Physiology 123:167-182.
   
  Miller, M.J., A.S. Hejazi, S.H. Wei, I. Parker, and M.D. Cahalan. 2004. T cell repertoire scanning is promoted by dynamic dendritic cell behavior and random T cell motility in the lymph node. Proceedings of the National Academy of Sciences U.S.A. 101:998-1003.
   
  Kozak, J.A. and M.D. Cahalan. 2003. MIC channels are inhibited by internal divalent cations but not ATP. Biophysical Journal 84:922-927.
   
  Kerschbaum, H.H., J.A. Kozak, and M.D. Cahalan. 2003. Polyvalent cations as permeant probes of MIC and TRPM7 pores. Biophysical Journal 84:2293-305.
   
  Miller, M.M., S.H. Wei, I. Parker, and M.D. Cahalan. 2003. Autonomous T cell trafficking examined in vivo using intravital two-photon microscopy. Proceedings of the National Academy of Sciences U.S.A. 100:2604-2609.
   
  Miller, M.M., S.H. Wei, I. Parker, and M.D. Cahalan. 2002. Two-photon imaging of lymphocyte motility and dynamic antigen responses in intact lymph node. Science 296:1869-1873.
   
Grants NIH NS-14609, "Molecular Mechanisms of Ion Channels in T Lymphocytes". 1978-present.
   
NIH GM-41514, "Functional Imaging of Lymphocyte Motility and Cell Interactions in Lymph Node". 1984-present.
   
Professional
Societies
Biophysical Society
Society of General Physiologists, Journal of General Physiology Editorial Board 1987-present
Physiological Reviews Editorial Board 2002-present
American Association of Immunologists
   
Graduate Programs Cellular and Molecular Biosciences

   
Research Center Institute for Immunology, Cancer Center
   
   
Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=2150
   
Last updated 07/21/2011