Dr. Yousang Gwack
Calcium channel function and regulation
53-266 CHS
310-794-2003
ygwack@mednet.ucla.edu

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Research Interests:

In many different cell types including the cells of the immune system, the depletion of intracellular endoplasmic reticulum Ca2+ stores by receptor stimulation triggers Ca2+ entry through plasma membrane store-operated Ca2+ channels known as Ca2+ release-activated Ca2+ (CRAC) channels. Although the CRAC current was defined electrophysiologically in the early 80s', the molecular identity of the CRAC channel stayed elusive till last year when we and two other groups discovered the gene encoding a critical subunit of the CRAC channels. The gene was name by me as Drosophila Orai (dOrai) and its mammalian homologues as Orai1, -2, -3 after discovery by genome-wide RNAi screen in Drosophila cells. The identification of Orai for the first time gives us a molecular handle to study the macromolecular structure and mechanism of regulation of CRAC channels. Presently we are analyzing the phenotype of Orai1 knock out mice to understand the physiological role of the CRAC channel function in the immune system and in the long term in other cell types where Ca2+/Calcineurin/NFAT signaling is known to play an important role.

Schematic diagram showing two phases of activation of store-operated Ca2+ entry in T cells. The ER Ca2+ store is depleted by IP3 produced by PLC-gamma activated through the ligand-receptor engagement (Phase 1). The depletion can trigger opening of the CRAC channels on the plasma membrane (Phase 2). The long sought genes encoding the CRAC channel component was found by genome-wide RNAi screen (Nature, 441, p179) and named as “Orai”.

Representative Publications:

Gwack Y, Sharma S, Nardone J, Tanasa B, Iuga A, Srikanth S, Okamura H, Bolton D, Feske S, Hogan PG, Rao A. A genome-wide Drosophila RNAi screen identifies DYRK as a novel regulator of NFAT. Nature (letter), 2006 Jun 1;441(7093):646-50.

Feske S*, Gwack Y*, Prakriya M, Srikanth S, Puppel S-H, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A. A mutation in Orai1 causes immune deficiency by abrogating store-operated Ca2+ entry and CRAC channel function, Nature (Article), 2006 May 11;441(7090):179-85. *Equal Contribution.

Prakriya M*, Feske S*, Gwack Y*, Srikanth S, Rao A, Hogan PG. Orai1 is an essential component of the CRAC channel pore, Nature. 2006 Sep 14;443(7108):230-3. *Equal Contribution.

Link to my complete PubMed bibliography: