T and B lymphocytes are central to immune defenses against infections and cancer but also drive autoimmune diseases (e.g., rheumatoid arthritis, SLE, multiple sclerosis), inflammatory disorders (colitis, psoriasis), and allergies/asthma. Ion channels and transporters (ICTs) sit at the heart of immune cell biology, regulating fundamental processes including growth, differentiation, metabolism, and gene expression. Beyond classical ions such as calcium, zinc, sodium, and chloride, ICTs also transport small molecules including metabolites, amino acids, and immune mediators. Despite the existence of more than one thousand ICTs, only 15–20 have been established as regulators of immune function — among them the calcium channel ORAI1 and the potassium channels Kv1.3 and KCa3.1, which are essential for T cell-mediated immunity.
Many fundamental questions remain unanswered: Which ICTs are expressed and functional across different lymphoid and myeloid cell types? What downstream signaling, metabolic, and epigenetic pathways do they engage? How do ICTs orchestrate complex immune responses to infection, tumors, or self-antigens? And can targeting immune cell ion channels lead to safe and effective treatments for autoimmune disease, allergy, or cancer?
My laboratory addresses these questions through mechanistic and physiological studies in human and mouse immune cells. Our work builds on the landmark discovery of ORAI1 as the gene encoding the calcium release-activated calcium (CRAC) channel and the identification of CRAC channelopathy — a novel inborn error of immunity caused by mutations in ORAI1 and its activator STIM1. We have since uncovered several additional ICTs that regulate T and B cell function, including the chloride and cGAMP channel LRRC8C, multiple members of the ZIP family of zinc transporters, the sodium/bicarbonate cotransporter NBCn1/SLC4A7, and the copper transporter CTR1/SLC31A1.
Our research aims to discover and characterize novel immune ICTs, elucidate their molecular and immunological mechanisms, and ultimately lay the groundwork for an entirely new class of immunomodulatory therapies.