Dr. Jinwei ZhangInstitute of Biomedical and Clinical Sciences, Medical School, College of Medicine and Health, University of Exeter, UK
Speech Title: Targeting the WNK-SPAK/OSR1 Pathway and Cation-Chloride Cotransporters for Diseases Therapy
Abstract: The SLC12 family of cation-chloride-cotransporters (CCCs) comprises of potassium chloride cotransporters (KCCs)-mediated Cl- extrusion and sodium potassium chloride cotransporters (N[K]CCs)-mediated Cl- loading. The CCCs play vital roles in cell volume regulation and ion homeostasis. In recent years, there have been considerable advances in our understanding of CCCs control mechanisms, particularly via the pathway containing the with-no-lysine [K] (WNK) and its downstream target kinases, SPS/Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress responsive 1 (OSR1) and their upstream E3 ubiquitin ligase complex comprising Kelch-like 3 (KLHL3) and Cullin 3 (CUL3), which has led to the discovery of novel inhibitory molecules. Our work has subsequently led to the development of a drug-like molecules targeting WNK-SPAK kinases, for the treatment of human diseases, e.g. Hypertension, Stroke etc..
Keywords: Cation-chloride-cotransporters; CUL3/KLHL3-WNK-SPAK/OSR1; Kinase inhibitors; Hypertension and Stroke
Biography: Dr Jinwei Zhang is an Associate Professor at the University of Exeter Medical School, UK. His laboratory studies ion channels, transporters, and signalling pathways that associated with human diseases, for examples, stroke that regulated by WNK-SPAK/OSR1-KCC2/NKCC1, hypertension that regulated by WNK-SPAK/OSR1-NCC, and concern with elucidating and targeting ion transporters, kinases, protein-protein interactions using genetic mouse models, small molecules, CRISPR/Cas9 gene-editing technologies, and electrophysiology to aid discovery and validation of new potential drug targets. He is internationally recognized for his expertise in cellular chloride homeostasis and cell volume regulation and drug discovery. He has published more than 70 articles in journals including Nature Medicine, Cell Metabolism, Neuron, Nature Communications, EMBO molecular medicine, Science Signalling, Human Molecular Genetics etc. and has achieved more than 2430 citations, H-index=28. He is an Associate Editor for the Frontiers in Pharmacology, and Frontiers in Physiology. He is currently a member of the editorial boards of 30 scientific journals, as well as a reviewer for more than 40 scientific journals.