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Research in the Feske lab is focused on calcium and ionic signaling in immune cells and its role in immune responses. We identified ORAI1 as the gene encoding the Ca²⁺ release-activated Ca²⁺ (CRAC) channel and showed that it forms the pore of the channel. We identified the first CRAC channel-deficient patients with mutations in ORAI1 and its activator STIM1 and thereby defined a new disease entity (CRAC channelopathy). Using knockout mice for Orai1, Orai2, Orai3, Stim1 and Stim2, we could show that CRAC channels are essential for physiological T cell functions during immunity to infection and antitumor immunity as well as pathological T cell functions in autoimmune diseases and inflammation. Current CRAC channel related research areas include the study of genetic defects of CRAC channel function in patients with mutations in ORAI1 and STIM1 genes, of mechanisms by which CRAC channels regulate adaptive and innate immunity to infection and T cell-mediated autoimmunity (including multiple sclerosis and colitis) and allergic airway inflammation. In recent years, the Feske lab has made substantial efforts to identify new ion channels and transporters (ICTs) that regulate immune responses by T cells, B cells and macrophages. Only a small fraction of the several hundred known ICTs are known to play a role in immune cells and immunity. Using expression analyses of ICTs in dozens of immune cell subsets and forward genetic screening approaches in primary immune cells, the lab is identifying new ion channels regulating immune responses. Examples of ICTs we identified to play a role in immune cells are LRRC8C, which transports Cl^- and the second messenger cGAMP in T cells, several zinc transporters, proton channels and other ICTs that are at various stages of investigation.

This seminar will be given online via Zoom. Details in attached poster.