Gene Encoding CRAC Channel
Background: CRAC stands for Ca2+-Release Activated Ca2+. When Ca2+ from the endoplasmic reticulum (a major store of Ca2+) is depleted, a CRAC channel, is activated to slowly replenish the endoplasmic reticulum. The CRAC channel is critical to the activation of T lymphocytes, mast cells and other hematopoietic cells, as it provides the primary route for the influx of calcium into these cells. Inhibition of the CRAC channel could, therefore, provide one of the most direct means of modulating the immune response for the treatment of multiple diseases and disorders.
Technology: Screening for molecules affecting CRAC current using RNA interference in Drosophila cell lines, Dr. Cahalan's team and three other groups of researchers have independently found several cofactors that are implicated in CRAC function. Dr. Cahalan's team identified cofactor Orai that forms CRAC channel allowing calcium to enter the cell. Further 75 RNAi hits that inhibit Ca2+ influx were identified.
Further Prof. Cahalan is planning to identify compounds that modulate activity of Orai and affect CRAC channel by blockage or enhancement. Such compounds could be used to prevent rejection of transplanted organs or to tone down the immune response in cases of autoimmune disease such as multiple sclerosis, type I diabetes, or rheumatoid arthritis.
Application: Novel drug target to modulate activity of CRAC channels
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