Michael D. Cahalan
University of California, Irvine
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Primary Section: 23, Physiology and Pharmacology Secondary Section: 43, Immunology and Inflammation Membership Type:
Member
(elected 2010)
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Research Interests
I have pursued a single-cell approach to investigate the immune system. By recording membrane current in individual T lymphocytes, my research group identified five distinctive types of ion channel and found agents that block them. Using channel blockers, we showed that specific calcium, potassium, and chloride ion channels comprise a functional network and are required during an immune response for changes in gene expression, cytokine secretion, cell proliferation, and motility; as well as controlling membrane potential, intracellular calcium levels, and cell volume homeostasis. Agents that block a specific voltage-gated potassium channel, named Kv1.3, are proving effective in treating animal models of inflammatory and autoimmune disorders. My laboratory has also worked on a voltage-independent calcium channel in T lymphocytes that is triggered to open following recognition of antigen. RNA interference screening led us to the discovery of two proteins -- Stim and Orai -- that together form the molecular basis of the calcium channel. We are presently investigating how STIM proteins in the endoplasmic reticulum activate plasma membrane Orai subunits to form conducting Ca2+ channels. In addition, we are using two-photon microscopy to investigate cellular choreography in lymphoid organs and to evaluate candidate immunosuppressants in vivo.
