Dr Jinwei Zhang
Lecturer (Education and Research)
+44 (0)1392 72 3828
Hatherly Building, University of Exeter, Prince of Wales Road, Exeter, EX4 4PS, UK
Dr Jinwei Zhang has a very wide-ranging expertise, which makes him uniquely positioned to develop research at the interface between fields. He gained a solid theory and practice of training in the field of microbial biotechnology, biochemistry and molecular biology, enzymology, pharmacology, drug discovery, signaling transduction during his academic degrees and postdoc trainings. He studies signalling pathways that associated with human diseases, for examples, Parkinson's Disease (LRRK2), neuropsychiatric disorders (WNK-SPAK-KCC2) and hypertension (CUL3/KLHL3-WNK-SPAK-NCC) and concern with elucidating and targeting ion transporters, kinases, protein-protein interactions using genetic mouse models, mass spectrometry, small molecules and CRISPR/Cas9 knock-in and knock-out technologies to aid discovery and validation of new potential drug targets
- BSc, 2003, Fujian Normal University (Fuzhou City), China
- MSc, 2007, Xiamen University (Xiamen City), and the Third Institute of Oceanography (Xiamen City), State Oceanic Administration, China
- PhD, 2011, Newcastle University, Newcastle upon Tyne, UK
Dr Jinwei Zhang obtained a BSc degree in Microbial Biotechnology from Fujian Normal University China in 2003. While there, he studied mutagenesis of Aspergillus niger for higher yield of multicomponent enzymes. He then obtained a MSc degree in Marine Microbial Biochemistry and Molecular Biology at The Third Institute of Oceanography (Xiamen), State Oceanic Administration China in 2007. While there, he studied marine ecology and cold-adapted enzymes from deep-sea becteria. He then obtained a PhD degree in Biotechnology from Newcastle University UK in 2011. While there, he studied natural bioactive compounds and electricity generation by marine microorganisms. Since 2011, he pursued his interest in cellular signaling with a post-doctoral fellowship at the Medical Research Council Protein Phosphorylation and Ubiquitylation Unit in Dundee with Professor Dario Alessi (FRS). While there, he studied LRRK2 associated Parkinson's disease in collaboration with Professor Nathanael Gray at Harvard Medical School, and contributed to the discovery of the most potent LRRK2 kinase inhibitors TAE684 and TTT3002, most selective LRRK2 inhibitor GSK2578215A, and the first brain penetrable LRRK2 inhibitors HG-10-102-01 and JH-II-127. Since 2013, his research focuses broadly on CUL3/KLHL3-WNKs-SPAK/OSR1-CCCs signaling in ion homeostasis and human diseases (neuropsychiatric disorders and hypertension) in collaboration with Professor Kristopher Kahle at Yale University School of Medicine. He joined the Faculty of the University of Exeter Medical School and started his own laboratory in 2017 where his KCC2 investigations can gain greater impact by integration with the clinical resources and basic science research at The Institute of Biomedical and Clinical Sciences.
Homeostasis of the intracellular ionic milieu is essential for the proper functioning of all cells and a diverse group of cellular processes. The mechanisms responsible for the homeostasis of the intracellular Cl- concentration [Cl-]i, for example, significantly impacts the rate of fluid secretion or absorption across epithelia; how red blood cells counteract potentially damaging osmotic-induced cell swelling or shrinkage; and whether the GABA neurotransmitter excites or inhibits post-synaptic neurons.
The neuronal potassium-chloride co-transporter KCC2 is one of the molecules effectively controlling intracellular Cl- and adjusting the inhibitory strength of GABA. KCC2 hypofunction results in decreased inhibition and increased network hyperexcitability that underlies numerous neurological disorders including epilepsy, autism, post-surgical complication, neuropathic pain and neuropsychiatric disorders.
KCC2 activity is decreased in most diseases associated with GABAergic disinhibition. A positive modulator (i.e., “activator”) of KCC2 might be effective in reversing the effects of KCC2 downregulation and lowering [Cl–]i to restore GABAergic inhibition.
Previous work in Lifton Lab at Yale revealed that activity of KCC2 is critically controlled by phosphorylation of two highly conserved residues (KCC2 Thr906/Thr1007) (Cell, 2009). Dr Zhang's recent work in Alessi Lab at Dundee and Kahle Lab at Yale discovered that it is WNK-regulated SPAK/OSR1 kinases that directly phosphorylate KCC2 at Thr1007 and Thr906, thereby leading to its inhibition (Biochem. J. 2014, Sci. Signal. 2015, Sci. Rep. 2016, Nat. Comm. 2017). This has potential implications for the therapeutic modulation of neurological disorders by targeting of WNK-SPAK/OSR1 with kinase inhibitors, with a new strategy to enhance cellular chloride extrusion.
Dr Zhang and his colleagues aim to study Cul3/KLHL3-WNK-SPAK signalling pathway and KCC2 mouse models involved in control of the KCC2 activity and downstream GABAergic neurotransmission during neuronal development under physiological conditions and in models of epilepsy and autism, and to develop small molecular compounds that suppress WNK-SPAK kinase signalling pathway and therefore to activate KCC2.
Publications by category
Publications by year
Jinwei_Zhang Details from cache as at 2018-11-21 04:41:49
- Bursary Award, Parkinson's UK (2012)
- Outstanding Young Scientist Award, American Oil Chemists Society (2010)
- Travel Grant Award, European Section of the American Oil Chemists Society (2010)
- Second-class Award of Publication, Journal 'Progress in Modern Biomedicine’ (2010)
- BBSRC-Dorothy Hodgkin Postgraduate Award (DHPA), Newcastle University UK (2008-2011)
- Third-class Award of Publication, State Oceanic Administration, China (2008)
- Outstanding Young Scientist Award, Chinese Enzyme Engineering Society (2005)
- Fujian Normal University Scholarship Award (2009-2003)
Dr Zhang contributes to the following undergraduate modules,
Anatomy and Physiology (PAM1011)
Integrated Human Physiology (CSC1005)
Translational Medical Science (CSC4019)
Fundamental Skills for Medical Scientists (CSC1004)
Academic and Professional Support (CSC1905)