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.

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Primary Section

Section 23: Physiology and Pharmacology

Secondary Section

Section 43: Immunology and Inflammation