A major recent focus of my laboratory is the discovery and characterization of novel ion channels and transporters (ICTs) that regulate the function of T cells, B cells, and macrophages across diverse immune responses. Combining expression analyses of ICTs in human and mouse immune cell subsets with shRNA- and CRISPR/Cas9-based forward genetic screens, we have identified >10 new ICTs that govern multiple aspects of immune cell function in the context of infection, antitumor immunity, and autoimmunity. In CD4⁺ T cells, we identified the volume-regulated chloride channel LRRC8C and demonstrated that it transports the dinucleotide cGAMP to activate STING signaling, thereby controlling T cell expansion and immune responses. We further showed that CLNS1A — originally reported as a chloride channel subunit — is essential for the proinflammatory function of Th17 cells in models of multiple sclerosis and inflammatory bowel disease, acting as a cofactor of the protein arginine methyltransferase PRMT5 to regulate DNA repair. Additionally, the copper transporter SLC31A1 was found to regulate CD4⁺ T cell metabolism and pathogenic Th17 cell function, with consequent effects on autoimmunity. In B cells, we identified the amino acid transporter SLC7A5 and the bicarbonate transporter SLC4A7 as regulators of B cell metabolism through mTORC1, controlling plasma cell differentiation and antibody production.
Ongoing work in the laboratory is focused on elucidating the mechanisms by which ZIP family zinc transporters, SLC31A1, Ca2+ and Na+ transporters, and other ICTs govern T and B cell function and immune responses. The ultimate goal of these studies is to identify and validate novel therapeutic targets for modulating immunity in autoimmunity, cancer, and inflammatory disease.