Research groupDepartment

Thomas J. Jentsch

Physiology and Pathology of Ion Transport

Portrait

We study ion transport across cellular membranes using techniques of biophysics, cell and molecular biology, and genetically modified mouse models. This work has provided insights into cellular phenotypes including impaired endocytosis and lysosomal storage, and pathologies such as neurodegeneration, epilepsy, deafness, osteopetrosis, kidney stones, hypertension and much more.

Profile

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.

 

Research Overview

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.

Head

About Thomas Jentsch

Thomas J. Jentsch studied both medicine and physics at the FU Berlin. After having obtained doctoral degrees in both areas, he did postdoctoral research in transport physiology in Berlin and molecular cell biology with Harvey Lodish at the Whitehead Institute/MIT. In 1988, he was a founding member of the Center for Molecular Neurobiology Hamburg (ZMNH), where he made his first seminal discoveries. In 2006 he moved his lab to Berlin, joining the FMP and MDC. Thomas Jentsch’s research is concerned with ion transport in the broadest sense. He is arguably the world leader in the field of chloride transport.

'My lab is broadly interested in ion transport processes. Our research spans the whole spectrum from newly identifying ‘novel’ ion channels to studying how their structure determines biophysical transport properties, to determining their role in cellular and organismal processes. Besides plasma membrane channels, we elucidate the roles of ion transport in intracellular organelles. A strong focus is on the role of ion transport in physiology and disease, which we address with genetic mouse models and human genetics.

We are particularly interested in anion channels. We discovered, for the first time, the CLC family of anion channels and transporters (1990), the molecular identities of volume-regulated VRAC/LRRC8 anion channels (2014) and of acid-activated ASOR/TMEM206 Cl channels (2019). We discovered and/or analyzed the roles of CLCs in myotonia, kidney stones, osteopetrosis, neurodegeneration, leukodystrophy, blindness, deafness, infertility, renal salt loss and aldosteronism.

We also discovered all four neuronal Kv7 K channels (KCNQ2-KCNQ5), their role in epilepsy and deafness, and studied the (patho-)physiology of the K-Cl cotransporters KCC2, -3, and -4 using mouse models.’

Lab Coordinator

Dr. Norma Nitschke

Lab coordinator, Jentsch Group


Research Section

Molecular Physiology & Cell Biology

Members

 People

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Job offers

Curious about novel roles of ion transport processes in the physiology and pathology of various organs, and interested in investigating those using a diverse set of methods and approaches? We are continuously looking for highly motivated postdocs to join our international and interdisciplinary team. For projects investigating the role of vesicular anion transport in endolysosomal function from a novel angle, candidates should have an education in natural sciences or medicine and desirably a solid background in cell biology and physiology. For other projects, applications from electrophysiologists are also welcome. Please direct your application to Prof. Thomas Jentsch (jentsch(at)fmp-berlin.de), including a CV, a motivation letter, and references.