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Richard Lewis

Academic Appointments

Contact Information

  • Academic Offices
    Personal Information
    Email
    Administrative Contact
    Jzesern Tan Administrative Assistant Tel Work 725-4900

Professional Snapshot

Administrative Appointments

  • Chair, Stanford University School of Medicine - Molecular & Cellular Physiology (2004 - present)

Honors and Awards

  • Junior Faculty Scholar, HHMI (1996-1998)

Education & Community

Professional Education

  • B.S., Yale University, Molec Biophysics & Biochem (1978)
  • Ph.D., California Inst. of Technology, Neurobiology (1985)

Scientific Focus

Research Interests

Research in our laboratory is focused on the molecular mechanisms of calcium signaling through store-operated Ca2+ channels (SOCs). This class of ion channels is regulated in a unique way, by the depletion of Ca2+ from the lumen of the endoplasmic reticulum (ER) which normally occurs following stimulation of cell surface receptors that generate IP3. They are expressed in practically all cells, where they contribute to diverse functions including secretion, gene expression, and cell differentiation. A SOC called the Ca2+ release-activated Ca2+ channel, or CRAC channel, is particularly important in T cells, where it generates sustained Ca2+ signals that are essential for triggering T cells to proliferate and carry out immune functions. Loss of function of the CRAC channel by a single mutation in its structural gene leads to a devastating severe combined immunodeficiency (SCID) syndrome in humans.

A major effort in the lab is to understand how the depletion of Ca2+ from the ER triggers the opening of CRAC channels in the plasma membrane. Since the recent discovery of genes encoding the ER Ca2+ sensor (STIM1) and the CRAC channel (Orai1), we have made rapid progress in revealing the choreographic nature of this process. Following store depletion, STIM1 moves from locations throughout the ER to accumulate in ER subregions positioned within 10-25 nm of the plasma membrane (PM). Simultaneously, the CRAC channel gathers at corresponding sites in the PM directly opposite STIM1, where it is opened through an interaction with STIM1. This is an unprecedented mechanism for channel activation, in which a stimulus acts to bring a channel and its activator/sensor together for interaction across apposed membrane compartments. We are currently studying how changes in ER Ca2+ drive the redistribution of STIM1 and the mechanism by which STIM1 and Orai1 interact across the ER-PM gap. For these studies we combine protein engineering with patch-clamp electrophysiology...

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