Thomas J. Jentsch

We aim to understand ion transport processes from the molecular to the cellular and up to the level of the organism. The latter levels are addressed with  genetic mouse models and the analysis of human genetic diseases. In particular, we study CLC Cl^- channels and transporters and, more recently, volume-regulated VRAC/LRRC8 and acid-activated ASOR/TMEM206 channels. Key research areas are structure/function analysis, neurobiology, extracellular signaling, volume regulation, and cell biology of the endosomal-lysosomal system. We investigate many organs, including the brain, inner ear, kidney, the immune system and endocrine organs such as the adrenal gland and endocrine pancreas. After our breakthrough in identifying the long-sought volume-regulated anion channel VRAC in 2014, we elucidate its diverse functions. Our identification of ASOR in 2019 opened yet another new area of research. Our analysis of a large collection of mouse models has provided crucial biological and medically relevant insights.

Ion transport processes play crucial roles in neuronal excitability, signal transduction, transport of salt, water, and other substances across epithelia, and the homeostasis of extracellular, cytosolic, and vesicular compartments.

Our highly interdisciplinary investigations stretch from structure-function studies and biophysics to cell biological aspects like endocytosis and to the physiological and systemic role of particular transport proteins. We have identified several human diseases that are due to mutations in ion channels and have generated various knock-out mouse models. Their phenotypes yield important insights into the normal role of particular ion transporters and indicate candidate genes for human diseases. In accord with the broad importance of ion transport, these disorders include epilepsy and neurodegeneration, deafness, kidney stones, urinary protein loss, hypertension, thick bones (osteopetrosis), and primary hyperaldosteronism, among others. Our work bridges the gap between molecular studies and systems biology.

Our research focuses currently on CLC chloride channels and transporter, VRAC volume-regulated anion channels, and the recently identified acid-activated anion channel ASOR. At the same time, we explore several new directions. In 2014, we have established the long-sought molecular identity of VRAC, which is ubiquitously expressed in mammalian cells. VRAC not only plays a central role in cell volume regulation, but also in amino-acid and neurotransmitter release. VRAC is believed to be important in several physiological and pathological conditions. We have already shown that VRAC plays a role in tumor drug resistance and in insulin secretion by pancreatic β-cells and that VRAC enhances innate immunity by transporting the messenger molecule cGAMP. Recently (2019) we have identified still another chloride channel, ASOR. To focus on these new areas, we have closed our long-standing, very successful research programs on KCNQ potassium channels, KCC K-Cl-cotransporters, and TMEM16 (Anoctamin) Ca-activated chloride channels.