COLLEGE OF MEDICINE AND HEALTH
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Dr Jinwei Zhang

Dr Jinwei Zhang

Lecturer (Education and Research)

 +44 (0)1392 72 3828

 Hatherly D9

 

Hatherly Building, University of Exeter, Prince of Wales Road, Exeter, EX4 4PS, UK

Overview

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 marine microbial biotechnology, natural bioactive compounds, 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.

Qualifications

  • 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

Career

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 bacteria. He then obtained a PhD degree in Biotechnology from Newcastle University UK in 2011. While there, he studied natural bioactive compounds and green energry (electricity generation) from marine microorganisms.

Since 2011, Jinwei pursued his interest in cellular signalling with a post-doctoral fellowship at the Medical Research Council (MRC)- Protein Phosphorylation and Ubiquitination Unit (PPU) 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 2014, Jinwei's research focused on CUL3/KLHL3-WNKs-SPAK/OSR1-CCCs signalling in cellular chloride homeostasis and cell volume regulation in collaboration with Professor Kristopher Kahle at Yale University School of Medicine. In 2017, Jinwei joined the Faculty of the University of Exeter Medical School, where his KCC2/ NKCC1 investigations can gain greater impact by integration with the clinical resources and basic science research at The Institute of Biomedical and Clinical Sciences.

Recent research in Zhang Laboratory has greatly improved our understanding of the function of Chloride ion transporters, e.g. NCC, NKCC2, NKCC1, KCC2 and KCC3, and their upstream regulatory mechanism by the WNK-SPAK/OSR1 signalling pathway in mammalian cells and tissues under physiological and pathological conditions (Cell Metabolism 2017; Nature Medicine 2017; Nature Communications 2017; eLife 2018; Neuron 2019; Science Signalling 2019a, and Science Signalling 2019b), and subsequently led to the development of a drug-like molecular ZT-1a (Nature Communications 2020; US Patent App. 16/588,751).  Brain swelling after a stroke or epilepsy is a common and devastating problem for individuals and their families. This current discovery could address the urgent need for treatment that could provide an effective alternative to invasive surgery.

Links

Research group links

Research

Research interests

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.

Research networks

• Dario Alessi (MRC-PPU, University of Dundee, UK)
• Andrew Trevelyan (Newcastle University, UK)
• Nathanael Gray (Harvard Medical School - Harvard University, USA)
• Kristopher Kahle (Yale School of Medicine - Yale University, USA)
• Xianming Deng (Xiamen University, China)
• Dandan Sun (University of Pittsburgh, USA)
• Igor Medina  (Aix- Marseille University, INSERM, Marseille, France)
• Anna-Maria Hartmann (Carl von Ossietzky University Oldenburg, Germany)
 

Links


Publications

Key publications | Publications by category | Publications by year

Key publications

Zhang J, Bhuiyan MIH, Zhang T, Karimy J, Wu Z, Pigott VM, Zhang J, Huang H, Hassan MN, Skrzypiec AE, et al (2020). Modulation of brain cation-Cl− cotransport via the SPAK kinase inhibitor ZT-1a. Nature Communications, 7, 78-78. Full text.
Heubl M, Zhang J, Pressey JC, Al Awabdh S, Renner M, Gomez-Castro F, Moutkine I, Eugène E, Russeau M, Kahle KT, et al (2017). GABAA receptor dependent synaptic inhibition rapidly tunes KCC2 activity via the Cl--sensitive WNK1 kinase. Nat Commun, 8(1). Abstract.  Author URL.  Full text.
Karimy JK, Zhang J, Kurland DB, Theriault BC, Duran D, Stokum JA, Furey CG, Zhou X, Mansuri MS, Montejo J, et al (2017). Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus. Nature Medicine, 23(8), 997-1003. Abstract.  Full text.
Shekarabi M, Zhang J, Khanna AR, Ellison DH, Delpire E, Kahle KT (2017). WNK Kinase Signaling in Ion Homeostasis and Human Disease. Cell Metabolism, 25(2), 285-299. Full text.
Zhang J, Deng X, Kahle KT (2016). Leveraging unique structural characteristics of WNK kinases to achieve therapeutic inhibition. Science Signaling, 9(450), pe3-pe3. Full text.
Zhang J, Siew K, Macartney T, O'Shaughnessy KM, Alessi DR (2015). Critical role of the SPAK protein kinase CCT domain in controlling blood pressure. Hum Mol Genet, 24(16), 4545-4558. Abstract.  Author URL.  Full text.

Publications by category

Journal articles

Chen Z, Zhang J, Heilig R, Sorrell FJ, D’Angiolella V, Fischer R, Alessi DR, Bullock AN (In Press). Sequence and structural variations determining the recruitment of WNK kinases to the KLHL3 E3 ligase.  Abstract.
Delmotte Q, Medina I, Hamze M, Buhler E, Zhang J, Belgacem YH, Porcher C (In Press). Smoothened receptor Signaling regulates the developmental shift of GABA polarity in rat somatosensory cortex.  Abstract.
Zhang J, Bhuiyan MIH, Zhang T, Karimy J, Wu Z, Pigott VM, Zhang J, Huang H, Hassan MN, Skrzypiec AE, et al (2020). Modulation of brain cation-Cl− cotransport via the SPAK kinase inhibitor ZT-1a. Nature Communications, 7, 78-78. Full text.
Robert SM, Reeves BC, Alper SL, Zhang J, Kahle KT (2020). New drugs on the horizon for cerebral edema: what’s in the clinical development pipeline?. Expert Opinion on Investigational Drugs, 1-7. Full text.
Meor Azlan NF, Koeners MP, Zhang J (2020). Regulatory control of the Na-Cl co-transporter NCC and its therapeutic potential for hypertension. Acta Pharmaceutica Sinica B Full text.
Meor Azlan NF, Zhang J (2020). Role of the Cation-chloride-cotransporters in Cardiovascular Disease. Cells, 9(10). Abstract.  Full text.
Delmotte Q, Hamze M, Medina I, Buhler E, Zhang J, Belgacem YH, Porcher C (2020). Smoothened receptor Signaling regulates the developmental shift of GABA polarity in rat somatosensory cortex. J Cell Sci Abstract.  Author URL.  Full text.
Zhang J, Cordshagen A, Medina I, Nothwang HG, Wisniewski JR, Winklhofer M, Hartmann A-M (2020). Staurosporine and NEM mainly impair WNK-SPAK/OSR1 mediated phosphorylation of KCC2 and NKCC1. PLOS ONE, 15(5), e0232967-e0232967. Full text.
Brown A, Meor Azlan NF, Wu Z, Zhang J (2020). WNK-SPAK/OSR1-NCC kinase signaling pathway as a novel target for the treatment of salt-sensitive hypertension. Acta Pharmacologica Sinica Full text.
Tillman L, Zhang J (2019). Crossing the Chloride Channel: the Current and Potential Therapeutic Value of the Neuronal K+-Cl- Cotransporter KCC2. BioMed Research International, 2019, 1-12. Full text.
Watanabe M, Zhang J, Mansuri MS, Duan J, Karimy JK, Delpire E, Alper SL, Lifton RP, Fukuda A, Kahle KT, et al (2019). Developmentally regulated KCC2 phosphorylation is essential for dynamic GABA-mediated inhibition and survival. Science Signaling, 12(603) aaw9315 Full text.
Pisella LI, Gaiarsa J-L, Diabira D, Zhang J, Khalilov I, Duan J, Kahle KT, Medina I (2019). Impaired regulation of KCC2 phosphorylation leads to neuronal network dysfunction and neurodevelopmental pathology. Science Signaling, 12(603), eaay0300-eaay0300. Abstract.  Full text.
Zhang J (2019). Meet Our Editorial Board Member. Current Signal Transduction Therapy, 14(1), 1-2.
Duran D, Zeng X, Jin SC, Choi J, Nelson-Williams C, Yatsula B, Gaillard J, Furey CG, Lu Q, Timberlake AT, et al (2019). Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation. Neuron, 101(3), 429-443.e4. Abstract.  Full text.
Huang H, Song S, Banerjee S, Jiang T, Zhang J, Kahle KT, Sun D, Zhang Z (2019). The WNK-SPAK/OSR1 kinases and the cation-chloride cotransporters as therapeutic targets for neurological diseases. Aging and Disease, 10 Full text.
Wang J, Erazo T, Ferguson FM, Buckley DL, Gomez N, Muñoz-Guardiola P, Diéguez-Martínez N, Deng X, Hao M, Massefski W, et al (2018). Structural and atropisomeric factors governing the selectivity of pyrimido-benzodiazipinones as inhibitors of kinases and bromodomains. ACS Chemical Biology Abstract.  Full text.
Dumon C, Diabira D, Chudotvorova I, Bader F, Sahin S, Zhang J, Porcher C, Wayman G, Medina I, Gaiarsa J-L, et al (2018). The adipocyte hormone leptin sets the emergence of hippocampal inhibition in mice. eLife, 7, e36726-e36726. Full text.
Zhang J, Burgess JG (2017). Enhanced eicosapentaenoic acid production by a new deep-sea marine bacterium Shewanella electrodiphila MAR441(T). PLOS ONE, 12(11). Author URL.  Full text.
Heubl M, Zhang J, Pressey JC, Al Awabdh S, Renner M, Gomez-Castro F, Moutkine I, Eugène E, Russeau M, Kahle KT, et al (2017). GABAA receptor dependent synaptic inhibition rapidly tunes KCC2 activity via the Cl--sensitive WNK1 kinase. Nat Commun, 8(1). Abstract.  Author URL.  Full text.
Karimy JK, Zhang J, Kurland DB, Theriault BC, Duran D, Stokum JA, Furey CG, Zhou X, Mansuri MS, Montejo J, et al (2017). Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus. Nature Medicine, 23(8), 997-1003. Abstract.  Full text.
Zhang J, Karimy JK, Delpire E, Kahle KT (2017). Pharmacological targeting of SPAK kinase in disorders of impaired epithelial transport. Expert Opinion on Therapeutic Targets, 21(8), 795-804. Abstract.  Full text.
Shekarabi M, Zhang J, Khanna AR, Ellison DH, Delpire E, Kahle KT (2017). WNK Kinase Signaling in Ion Homeostasis and Human Disease. Cell Metabolism, 25(2), 285-299. Full text.
Andrukhova O, Zhang J, Alessi D, Erben R (2016). Bone loss in KLHL3 knock-in mice characterized by a pseudohypoaldosteronism type II-like phenotype is mediated by renal PTH resistance. Bone Abstracts Full text.
Zhang J, Gao G, Begum G, Wang J, Khanna AR, Shmukler BE, Daubner GM, de los Heros P, Davies P, Varghese J, et al (2016). Functional kinomics establishes a critical node of volume-sensitive cation-Cl− cotransporter regulation in the mammalian brain. Scientific Reports, 6(1). Full text.
Kahle KT, Schmouth J-F, Lavastre V, Latremoliere A, Zhang J, Andrews N, Omura T, Laganière J, Rochefort D, Hince P, et al (2016). Inhibition of the kinase WNK1/HSN2 ameliorates neuropathic pain by restoring GABA inhibition. Science Signaling, 9(421), ra32-ra32. Full text.
Zhang J, Deng X, Kahle KT (2016). Leveraging unique structural characteristics of WNK kinases to achieve therapeutic inhibition. Science Signaling, 9(450), pe3-pe3. Full text.
Emami K, Nelson A, Hack E, Zhang J, Green DH, Caldwell GS, Mesbahi E (2016). MALDI-TOF Mass Spectrometry Discriminates Known Species and Marine Environmental Isolates of Pseudoalteromonas. Frontiers in Microbiology, 7 Full text.
Kahle KT, Flores B, Bharucha-Goebel D, Zhang J, Donkervoort S, Hegde M, Begum G, Duran D, Liang B, Sun D, et al (2016). Peripheral motor neuropathy is associated with defective kinase regulation of the KCC3 cotransporter. Science Signaling, 9(439), ra77-ra77. Full text.
Kazlauskaite A, Martínez‐Torres RJ, Wilkie S, Kumar A, Peltier J, Gonzalez A, Johnson C, Zhang J, Hope AG, Peggie M, et al (2015). Binding to serine 65‐phosphorylated ubiquitin primes Parkin for optimal. PINK. 1‐dependent phosphorylation and activation. EMBO reports, 16(8), 939-954. Full text.
Schumacher F, Siew K, Zhang J, Johnson C, Wood N, Cleary SE, Al Maskari RS, Ferryman JT, Hardege I, Yasmin, et al (2015). Characterisation of the Cullin‐3 mutation that causes a severe form of familial hypertension and hyperkalaemia. EMBO Molecular Medicine, 7(10), 1285-1306. Full text.
Zhang J, Siew K, Macartney T, O'Shaughnessy KM, Alessi DR (2015). Critical role of the SPAK protein kinase CCT domain in controlling blood pressure. Hum Mol Genet, 24(16), 4545-4558. Abstract.  Author URL.  Full text.
Hatcher JM, Zhang J, Choi HG, Ito G, Alessi DR, Gray NS (2015). Discovery of a Pyrrolopyrimidine (JH-II-127), a Highly Potent, Selective, and Brain Penetrant LRRK2 Inhibitor. ACS Med Chem Lett, 6(5), 584-589. Abstract.  Author URL.  Full text.
Zhang J, Burgess JG (2015). Shewanella electrodiphila sp. nov. a psychrotolerant bacterium isolated from Mid-Atlantic Ridge deep-sea sediments. Int J Syst Evol Microbiol, 65(9), 2882-2889. Abstract.  Author URL.  Full text.
Friedel P, Kahle KT, Zhang J, Hertz N, Pisella LI, Buhler E, Schaller F, Duan J, Khanna AR, Bishop PN, et al (2015). WNK1-regulated inhibitory phosphorylation of the KCC2 cotransporter maintains the depolarizing action of GABA in immature neurons. Science Signaling, 8(383), ra65-ra65. Full text.
Alessi DR, Zhang J, Khanna A, Hochdörfer T, Shang Y, Kahle KT (2014). The WNK-SPAK/OSR1 pathway: Master regulator of cation-chloride cotransporters. Science Signaling(334). Abstract.  Full text.
de Los Heros P, Alessi DR, Gourlay R, Campbell DG, Deak M, Macartney TJ, Kahle KT, Zhang J (2014). The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+ -Cl- co-transporters. Biochemical Journal, 458(3), 559-573. Abstract.  Full text.
Delbroek L, Van Kolen K, Steegmans L, da Cunha R, Mandemakers W, Daneels G, De Bock PJ, Zhang J, Gevaert K, De Strooper B, et al (2013). Development of an enzyme-linked immunosorbent assay for detection of cellular and in vivo LRRK2 S935 phosphorylation. Journal of Pharmaceutical and Biomedical Analysis, 76, 49-58. Abstract.
Yao C, Johnson WM, Gao Y, Wang W, Zhang J, Deak M, Alessi. DR, Zhu X, Mieyal JJ, Roder H, et al (2013). Kinase inhibitors arrest neurodegeneration in cell and C. elegans models of LRRK2 toxicity. Human Molecular Genetics, 22(2), 328-344. Abstract.  Full text.
Deng X, Elkins JM, Zhang J, Yang Q, Erazo T, Gomez N, Choi HG, Wang J, Dzamko N, Lee JD, et al (2013). Structural determinants for ERK5 (MAPK7) and leucine rich repeat kinase 2 activities of benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-ones. European Journal of Medicinal Chemistry, 70, 758-767. Abstract.
Choi HS, Zhang J, Deng X, Hatcher JM, Patricelli MP, Zhao Z, Alessi DR, Gray NS (2012). Brain penetrant LRRK2 inhibitor. ACS Medicinal Chemistry Letters, 3(8), 658-662. Abstract.  Full text.
Zhang J, Deng X, Choi HG, Alessi DR, Gray NS (2012). Characterization of TAE684 as a potent LRRK2 kinase inhibitor. Bioorganic and Medicinal Chemistry Letters, 22(5), 1864-1869. Abstract.  Full text.
Zhang. J, Zhang E, Scott K, Burgess JG (2012). Enhanced electricity production by use of reconstituted artificial consortia of estuarine bacteria grown as biofilms. Environmental Science and Technology, 46(5), 2984-2992. Abstract.
Reith AD, Bamborough P, Jandu K, Andreotti D, Mensah L, Dossang P, Choi HG, Deng X, Zhang J, Alessi DR, et al (2012). GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent- N-arylbenzamide LRRK2 kinase inhibitor. Bioorganic and Medicinal Chemistry Letters, 22(17), 5625-5629. Abstract.  Full text.
Zhang J, Zeng R (2011). Molecular cloning and expression of an extracellular α-amylase gene from an Antarctic deep sea psychrotolerant Pseudomonas stutzeri strain 7193. World Journal of Microbiology and Biotechnology, 27(4), 841-850. Abstract.
Zhang J, Zeng R (2008). Molecular cloning and expression of a cold-adapted lipase gene from an antarctic deep sea psychrotrophic bacterium Pseudomonas sp. 7323. Marine Biotechnology, 10(5), 612-621. Abstract.  Full text.
Zhang J, Zeng R (2008). Purification and characterization of a cold-adapted α-amylase produced by Nocardiopsis sp. 7326 isolated from Prydz Bay, Antarctic. Marine Biotechnology, 10(1), 75-82. Abstract.  Full text.
Zhang J, Lin S, Zeng R (2007). Cloning, expression, and characterization of a cold-adapted lipase gene from an antarctic deep-sea psychorotrophic bacterium, Psychobacter sp. 7195. Journal of Microbiology and Biotechnology, 17(4), 604-610. Abstract.  Full text.
Zhang J, Zeng R (2007). Isolation of antarctic psychrotrophilic Pseudomonas sp. 7197 and cloning of ppa gene for inorganic pyrophosphatase (PPase). Gaojishu Tongxin/Chinese High Technology Letters, 17(10), 1067-1071. Abstract.
Zhang J, Zeng R (2007). Psychrotrophic amylolytic bacteria from deep sea sediment of Prydz Bay, Antarctic: Diversity and characterization of amylases. World Journal of Microbiology and Biotechnology, 23(11), 1551-1557. Abstract.
Zhang J, Zeng R (2006). Cloning, expression and characterization of the cold active lipase (Lip3) from metagenomic DNA of an antarctic deep sea sediment. Progress in Biochemistry and Biophysics, 33(12), 1207-1214. Abstract.
Zhang J, Lian M, Zeng R (2006). Screening, fermentation condition and enzyme characterization of multicomponent enzymes producing Pseudomonas sp. NJ197. Chinese Journal of Applied and Environmental Biology, 12(5), 683-687. Abstract.

Conferences

Zhang J (2020). Activation of K+–Cl-–cotransporter KCC2 by inhibiting the WNK-SPAK kinase signalling as a novel therapeutic strategy for epilepsy. the 6th International Conference on Epilepsy & Treatment. 21st - 22nd Sep 2020. Abstract.
Zhang J (2019). Activation of K+–Cl-–cotransporter KCC2 by inhibiting the WNK-SPAK kinase signalling as a novel therapeutic strategy for epilepsy. 23rd International Conference on Neurology & Neurophysiology. 18th - 19th Mar 2019. Abstract.
Zhang J, Bhuiyan MIH, Zhang T, Karimy J, Wu Z, Kahle KT, Sun D, Deng X (2018). Restoration of brain water homeostasis and neurological function via a novel kinase-cotransporter modulator. Cell Symposia, Aging and Metabolism. 23rd - 25th Sep 2018. Abstract.
Bhuiyan MIH, Huang H, Zhang T, Molyneaux BJ, Poloyac SM, Zhang J, Deng X, Sun D (2018). WNK-SPAK-NKCC1 Cascade Activation Contributes to Worsened Brain Damage in Mice with Hypertension Comorbidity after Ischemic Stroke. Joint Hypertension 2018 Scientific Sessions. 6th - 9th Sep 2018. Abstract.
Karimy J, Zhang J, Medzhitov R, Simard M, Kahle K (2017). Inflammation-dependent cerebrospinal fluid hypersecretion from the choroid plexus in post-hemorrhagic hydrocephalus. 42nd FEBS congress. 10th - 14th Sep 2017. Abstract.
Kahle K, Schmouth J-F, Lavastre V, Latremoliere A, Zhang J, Andrews N, Dion PA, Duan J, Woolf CJ, Inquimbert P, et al (2016). Antagonism of Wnk/Hsn2 kinase ameliorates neuropathic pain by reducing maladaptive KCC2 inhibitory phosphorylation after nerve injury. 84th AANS Annual Scientific Meeting. 30th Apr - 4th May 2016. Abstract.
Siew K, Zhang J, Schumacher F, Alessi DR, Kurtz T, O'Shaughnessy KM (2015). Pulse waveform analysis reveals vascular contributions to Gordon Syndrome and Gitelman Syndrome blood pressure homeostasis. Proceedings Abstracts of the Physiological Society. 1st - 1st Jul 2015. Abstract.
Keith S, Jinwei Z, Dario R. A, Kevin M. O (2014). Disruption of STE20/SPS1-related Proline/Alanine-rich Kinase (SPAK) binding lowers blood pressure and recapitulates Gitelman syndrome in mice. American Society of Nephrology Kidney Week 2014 Annual Meeting.  Abstract.
Kahle KT, Gen G, Zhang J, Latremoliere A, Andrews N, Shang Y, Alessi D, Woolf C, Elledge S (2014). Promoting Endogenous GABAergic Analgesia via Kinase Modulation of Neuronal Ion Plasticity. 2014 CNS ANNUAL MEETING. 1st - 1st Aug 2014. Abstract.
Heros PDL, Zhang J, Gourlay R, Campbell D, Deak M, Macartney T, Kahle K, Alessi D (2014). SPAK/OSR1 kinases directly phosphorylate the K+-Cl- co-transporters. Federation of American Societies for Experimental Biology. 1st - 1st Apr 2014. Abstract.

Internet publications

Pinkas DM, Bufton JC, Bartual SG, Chen Z, Daubner GM, Schumacher F-R, Georghiou G, Zhang J, Sorrell FJ, Kurz T, et al (2018). Human with No Lysine Kinase 3 (WNK3). A Target Enabling Package, Version 4, 1-15. Full text.

Publications by year

In Press

Chen Z, Zhang J, Heilig R, Sorrell FJ, D’Angiolella V, Fischer R, Alessi DR, Bullock AN (In Press). Sequence and structural variations determining the recruitment of WNK kinases to the KLHL3 E3 ligase.  Abstract.
Delmotte Q, Medina I, Hamze M, Buhler E, Zhang J, Belgacem YH, Porcher C (In Press). Smoothened receptor Signaling regulates the developmental shift of GABA polarity in rat somatosensory cortex.  Abstract.

2020

Zhang J (2020). Activation of K+–Cl-–cotransporter KCC2 by inhibiting the WNK-SPAK kinase signalling as a novel therapeutic strategy for epilepsy. the 6th International Conference on Epilepsy & Treatment. 21st - 22nd Sep 2020. Abstract.
Zhang J, Bhuiyan MIH, Zhang T, Karimy J, Wu Z, Pigott VM, Zhang J, Huang H, Hassan MN, Skrzypiec AE, et al (2020). Modulation of brain cation-Cl− cotransport via the SPAK kinase inhibitor ZT-1a. Nature Communications, 7, 78-78. Full text.
Robert SM, Reeves BC, Alper SL, Zhang J, Kahle KT (2020). New drugs on the horizon for cerebral edema: what’s in the clinical development pipeline?. Expert Opinion on Investigational Drugs, 1-7. Full text.
Meor Azlan NF, Koeners MP, Zhang J (2020). Regulatory control of the Na-Cl co-transporter NCC and its therapeutic potential for hypertension. Acta Pharmaceutica Sinica B Full text.
Meor Azlan NF, Zhang J (2020). Role of the Cation-chloride-cotransporters in Cardiovascular Disease. Cells, 9(10). Abstract.  Full text.
Delmotte Q, Hamze M, Medina I, Buhler E, Zhang J, Belgacem YH, Porcher C (2020). Smoothened receptor Signaling regulates the developmental shift of GABA polarity in rat somatosensory cortex. J Cell Sci Abstract.  Author URL.  Full text.
Zhang J, Cordshagen A, Medina I, Nothwang HG, Wisniewski JR, Winklhofer M, Hartmann A-M (2020). Staurosporine and NEM mainly impair WNK-SPAK/OSR1 mediated phosphorylation of KCC2 and NKCC1. PLOS ONE, 15(5), e0232967-e0232967. Full text.
Brown A, Meor Azlan NF, Wu Z, Zhang J (2020). WNK-SPAK/OSR1-NCC kinase signaling pathway as a novel target for the treatment of salt-sensitive hypertension. Acta Pharmacologica Sinica Full text.

2019

Zhang J (2019). Activation of K+–Cl-–cotransporter KCC2 by inhibiting the WNK-SPAK kinase signalling as a novel therapeutic strategy for epilepsy. 23rd International Conference on Neurology & Neurophysiology. 18th - 19th Mar 2019. Abstract.
Tillman L, Zhang J (2019). Crossing the Chloride Channel: the Current and Potential Therapeutic Value of the Neuronal K+-Cl- Cotransporter KCC2. BioMed Research International, 2019, 1-12. Full text.
Watanabe M, Zhang J, Mansuri MS, Duan J, Karimy JK, Delpire E, Alper SL, Lifton RP, Fukuda A, Kahle KT, et al (2019). Developmentally regulated KCC2 phosphorylation is essential for dynamic GABA-mediated inhibition and survival. Science Signaling, 12(603) aaw9315 Full text.
Pisella LI, Gaiarsa J-L, Diabira D, Zhang J, Khalilov I, Duan J, Kahle KT, Medina I (2019). Impaired regulation of KCC2 phosphorylation leads to neuronal network dysfunction and neurodevelopmental pathology. Science Signaling, 12(603), eaay0300-eaay0300. Abstract.  Full text.
Zhang J (2019). Meet Our Editorial Board Member. Current Signal Transduction Therapy, 14(1), 1-2.
Duran D, Zeng X, Jin SC, Choi J, Nelson-Williams C, Yatsula B, Gaillard J, Furey CG, Lu Q, Timberlake AT, et al (2019). Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation. Neuron, 101(3), 429-443.e4. Abstract.  Full text.
Huang H, Song S, Banerjee S, Jiang T, Zhang J, Kahle KT, Sun D, Zhang Z (2019). The WNK-SPAK/OSR1 kinases and the cation-chloride cotransporters as therapeutic targets for neurological diseases. Aging and Disease, 10 Full text.

2018

Pinkas DM, Bufton JC, Bartual SG, Chen Z, Daubner GM, Schumacher F-R, Georghiou G, Zhang J, Sorrell FJ, Kurz T, et al (2018). Human with No Lysine Kinase 3 (WNK3). A Target Enabling Package, Version 4, 1-15. Full text.
Zhang J, Bhuiyan MIH, Zhang T, Karimy J, Wu Z, Kahle KT, Sun D, Deng X (2018). Restoration of brain water homeostasis and neurological function via a novel kinase-cotransporter modulator. Cell Symposia, Aging and Metabolism. 23rd - 25th Sep 2018. Abstract.
Wang J, Erazo T, Ferguson FM, Buckley DL, Gomez N, Muñoz-Guardiola P, Diéguez-Martínez N, Deng X, Hao M, Massefski W, et al (2018). Structural and atropisomeric factors governing the selectivity of pyrimido-benzodiazipinones as inhibitors of kinases and bromodomains. ACS Chemical Biology Abstract.  Full text.
Dumon C, Diabira D, Chudotvorova I, Bader F, Sahin S, Zhang J, Porcher C, Wayman G, Medina I, Gaiarsa J-L, et al (2018). The adipocyte hormone leptin sets the emergence of hippocampal inhibition in mice. eLife, 7, e36726-e36726. Full text.
Bhuiyan MIH, Huang H, Zhang T, Molyneaux BJ, Poloyac SM, Zhang J, Deng X, Sun D (2018). WNK-SPAK-NKCC1 Cascade Activation Contributes to Worsened Brain Damage in Mice with Hypertension Comorbidity after Ischemic Stroke. Joint Hypertension 2018 Scientific Sessions. 6th - 9th Sep 2018. Abstract.

2017

Zhang J, Burgess JG (2017). Enhanced eicosapentaenoic acid production by a new deep-sea marine bacterium Shewanella electrodiphila MAR441(T). PLOS ONE, 12(11). Author URL.  Full text.
Heubl M, Zhang J, Pressey JC, Al Awabdh S, Renner M, Gomez-Castro F, Moutkine I, Eugène E, Russeau M, Kahle KT, et al (2017). GABAA receptor dependent synaptic inhibition rapidly tunes KCC2 activity via the Cl--sensitive WNK1 kinase. Nat Commun, 8(1). Abstract.  Author URL.  Full text.
Karimy JK, Zhang J, Kurland DB, Theriault BC, Duran D, Stokum JA, Furey CG, Zhou X, Mansuri MS, Montejo J, et al (2017). Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus. Nature Medicine, 23(8), 997-1003. Abstract.  Full text.
Karimy J, Zhang J, Medzhitov R, Simard M, Kahle K (2017). Inflammation-dependent cerebrospinal fluid hypersecretion from the choroid plexus in post-hemorrhagic hydrocephalus. 42nd FEBS congress. 10th - 14th Sep 2017. Abstract.
Zhang J, Karimy JK, Delpire E, Kahle KT (2017). Pharmacological targeting of SPAK kinase in disorders of impaired epithelial transport. Expert Opinion on Therapeutic Targets, 21(8), 795-804. Abstract.  Full text.
Shekarabi M, Zhang J, Khanna AR, Ellison DH, Delpire E, Kahle KT (2017). WNK Kinase Signaling in Ion Homeostasis and Human Disease. Cell Metabolism, 25(2), 285-299. Full text.

2016

Kahle K, Schmouth J-F, Lavastre V, Latremoliere A, Zhang J, Andrews N, Dion PA, Duan J, Woolf CJ, Inquimbert P, et al (2016). Antagonism of Wnk/Hsn2 kinase ameliorates neuropathic pain by reducing maladaptive KCC2 inhibitory phosphorylation after nerve injury. 84th AANS Annual Scientific Meeting. 30th Apr - 4th May 2016. Abstract.
Andrukhova O, Zhang J, Alessi D, Erben R (2016). Bone loss in KLHL3 knock-in mice characterized by a pseudohypoaldosteronism type II-like phenotype is mediated by renal PTH resistance. Bone Abstracts Full text.
Zhang J, Gao G, Begum G, Wang J, Khanna AR, Shmukler BE, Daubner GM, de los Heros P, Davies P, Varghese J, et al (2016). Functional kinomics establishes a critical node of volume-sensitive cation-Cl− cotransporter regulation in the mammalian brain. Scientific Reports, 6(1). Full text.
Kahle KT, Schmouth J-F, Lavastre V, Latremoliere A, Zhang J, Andrews N, Omura T, Laganière J, Rochefort D, Hince P, et al (2016). Inhibition of the kinase WNK1/HSN2 ameliorates neuropathic pain by restoring GABA inhibition. Science Signaling, 9(421), ra32-ra32. Full text.
Zhang J, Deng X, Kahle KT (2016). Leveraging unique structural characteristics of WNK kinases to achieve therapeutic inhibition. Science Signaling, 9(450), pe3-pe3. Full text.
Emami K, Nelson A, Hack E, Zhang J, Green DH, Caldwell GS, Mesbahi E (2016). MALDI-TOF Mass Spectrometry Discriminates Known Species and Marine Environmental Isolates of Pseudoalteromonas. Frontiers in Microbiology, 7 Full text.
Kahle KT, Flores B, Bharucha-Goebel D, Zhang J, Donkervoort S, Hegde M, Begum G, Duran D, Liang B, Sun D, et al (2016). Peripheral motor neuropathy is associated with defective kinase regulation of the KCC3 cotransporter. Science Signaling, 9(439), ra77-ra77. Full text.

2015

Kazlauskaite A, Martínez‐Torres RJ, Wilkie S, Kumar A, Peltier J, Gonzalez A, Johnson C, Zhang J, Hope AG, Peggie M, et al (2015). Binding to serine 65‐phosphorylated ubiquitin primes Parkin for optimal. PINK. 1‐dependent phosphorylation and activation. EMBO reports, 16(8), 939-954. Full text.
Schumacher F, Siew K, Zhang J, Johnson C, Wood N, Cleary SE, Al Maskari RS, Ferryman JT, Hardege I, Yasmin, et al (2015). Characterisation of the Cullin‐3 mutation that causes a severe form of familial hypertension and hyperkalaemia. EMBO Molecular Medicine, 7(10), 1285-1306. Full text.
Zhang J, Siew K, Macartney T, O'Shaughnessy KM, Alessi DR (2015). Critical role of the SPAK protein kinase CCT domain in controlling blood pressure. Hum Mol Genet, 24(16), 4545-4558. Abstract.  Author URL.  Full text.
Hatcher JM, Zhang J, Choi HG, Ito G, Alessi DR, Gray NS (2015). Discovery of a Pyrrolopyrimidine (JH-II-127), a Highly Potent, Selective, and Brain Penetrant LRRK2 Inhibitor. ACS Med Chem Lett, 6(5), 584-589. Abstract.  Author URL.  Full text.
Siew K, Zhang J, Schumacher F, Alessi DR, Kurtz T, O'Shaughnessy KM (2015). Pulse waveform analysis reveals vascular contributions to Gordon Syndrome and Gitelman Syndrome blood pressure homeostasis. Proceedings Abstracts of the Physiological Society. 1st - 1st Jul 2015. Abstract.
Zhang J, Burgess JG (2015). Shewanella electrodiphila sp. nov. a psychrotolerant bacterium isolated from Mid-Atlantic Ridge deep-sea sediments. Int J Syst Evol Microbiol, 65(9), 2882-2889. Abstract.  Author URL.  Full text.
Friedel P, Kahle KT, Zhang J, Hertz N, Pisella LI, Buhler E, Schaller F, Duan J, Khanna AR, Bishop PN, et al (2015). WNK1-regulated inhibitory phosphorylation of the KCC2 cotransporter maintains the depolarizing action of GABA in immature neurons. Science Signaling, 8(383), ra65-ra65. Full text.

2014

Keith S, Jinwei Z, Dario R. A, Kevin M. O (2014). Disruption of STE20/SPS1-related Proline/Alanine-rich Kinase (SPAK) binding lowers blood pressure and recapitulates Gitelman syndrome in mice. American Society of Nephrology Kidney Week 2014 Annual Meeting.  Abstract.
Kahle KT, Gen G, Zhang J, Latremoliere A, Andrews N, Shang Y, Alessi D, Woolf C, Elledge S (2014). Promoting Endogenous GABAergic Analgesia via Kinase Modulation of Neuronal Ion Plasticity. 2014 CNS ANNUAL MEETING. 1st - 1st Aug 2014. Abstract.
Heros PDL, Zhang J, Gourlay R, Campbell D, Deak M, Macartney T, Kahle K, Alessi D (2014). SPAK/OSR1 kinases directly phosphorylate the K+-Cl- co-transporters. Federation of American Societies for Experimental Biology. 1st - 1st Apr 2014. Abstract.
Alessi DR, Zhang J, Khanna A, Hochdörfer T, Shang Y, Kahle KT (2014). The WNK-SPAK/OSR1 pathway: Master regulator of cation-chloride cotransporters. Science Signaling(334). Abstract.  Full text.
de Los Heros P, Alessi DR, Gourlay R, Campbell DG, Deak M, Macartney TJ, Kahle KT, Zhang J (2014). The WNK-regulated SPAK/OSR1 kinases directly phosphorylate and inhibit the K+ -Cl- co-transporters. Biochemical Journal, 458(3), 559-573. Abstract.  Full text.

2013

Delbroek L, Van Kolen K, Steegmans L, da Cunha R, Mandemakers W, Daneels G, De Bock PJ, Zhang J, Gevaert K, De Strooper B, et al (2013). Development of an enzyme-linked immunosorbent assay for detection of cellular and in vivo LRRK2 S935 phosphorylation. Journal of Pharmaceutical and Biomedical Analysis, 76, 49-58. Abstract.
Yao C, Johnson WM, Gao Y, Wang W, Zhang J, Deak M, Alessi. DR, Zhu X, Mieyal JJ, Roder H, et al (2013). Kinase inhibitors arrest neurodegeneration in cell and C. elegans models of LRRK2 toxicity. Human Molecular Genetics, 22(2), 328-344. Abstract.  Full text.
Deng X, Elkins JM, Zhang J, Yang Q, Erazo T, Gomez N, Choi HG, Wang J, Dzamko N, Lee JD, et al (2013). Structural determinants for ERK5 (MAPK7) and leucine rich repeat kinase 2 activities of benzo[e]pyrimido-[5,4-b]diazepine-6(11H)-ones. European Journal of Medicinal Chemistry, 70, 758-767. Abstract.

2012

Choi HS, Zhang J, Deng X, Hatcher JM, Patricelli MP, Zhao Z, Alessi DR, Gray NS (2012). Brain penetrant LRRK2 inhibitor. ACS Medicinal Chemistry Letters, 3(8), 658-662. Abstract.  Full text.
Zhang J, Deng X, Choi HG, Alessi DR, Gray NS (2012). Characterization of TAE684 as a potent LRRK2 kinase inhibitor. Bioorganic and Medicinal Chemistry Letters, 22(5), 1864-1869. Abstract.  Full text.
Zhang. J, Zhang E, Scott K, Burgess JG (2012). Enhanced electricity production by use of reconstituted artificial consortia of estuarine bacteria grown as biofilms. Environmental Science and Technology, 46(5), 2984-2992. Abstract.
Reith AD, Bamborough P, Jandu K, Andreotti D, Mensah L, Dossang P, Choi HG, Deng X, Zhang J, Alessi DR, et al (2012). GSK2578215A; a potent and highly selective 2-arylmethyloxy-5-substitutent- N-arylbenzamide LRRK2 kinase inhibitor. Bioorganic and Medicinal Chemistry Letters, 22(17), 5625-5629. Abstract.  Full text.

2011

Zhang J, Zeng R (2011). Molecular cloning and expression of an extracellular α-amylase gene from an Antarctic deep sea psychrotolerant Pseudomonas stutzeri strain 7193. World Journal of Microbiology and Biotechnology, 27(4), 841-850. Abstract.

2008

Zhang J, Zeng R (2008). Molecular cloning and expression of a cold-adapted lipase gene from an antarctic deep sea psychrotrophic bacterium Pseudomonas sp. 7323. Marine Biotechnology, 10(5), 612-621. Abstract.  Full text.
Zhang J, Zeng R (2008). Purification and characterization of a cold-adapted α-amylase produced by Nocardiopsis sp. 7326 isolated from Prydz Bay, Antarctic. Marine Biotechnology, 10(1), 75-82. Abstract.  Full text.

2007

Zhang J, Lin S, Zeng R (2007). Cloning, expression, and characterization of a cold-adapted lipase gene from an antarctic deep-sea psychorotrophic bacterium, Psychobacter sp. 7195. Journal of Microbiology and Biotechnology, 17(4), 604-610. Abstract.  Full text.
Zhang J, Zeng R (2007). Isolation of antarctic psychrotrophilic Pseudomonas sp. 7197 and cloning of ppa gene for inorganic pyrophosphatase (PPase). Gaojishu Tongxin/Chinese High Technology Letters, 17(10), 1067-1071. Abstract.
Zhang J, Zeng R (2007). Psychrotrophic amylolytic bacteria from deep sea sediment of Prydz Bay, Antarctic: Diversity and characterization of amylases. World Journal of Microbiology and Biotechnology, 23(11), 1551-1557. Abstract.

2006

Zhang J, Zeng R (2006). Cloning, expression and characterization of the cold active lipase (Lip3) from metagenomic DNA of an antarctic deep sea sediment. Progress in Biochemistry and Biophysics, 33(12), 1207-1214. Abstract.
Zhang J, Lian M, Zeng R (2006). Screening, fermentation condition and enzyme characterization of multicomponent enzymes producing Pseudomonas sp. NJ197. Chinese Journal of Applied and Environmental Biology, 12(5), 683-687. Abstract.

Jinwei_Zhang Details from cache as at 2020-10-23 21:11:21

Refresh publications

External Engagement and Impact

Awards

  • Above & Beyond Award (rigour), the University of Exeter (2019)
  • 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)

Editorial responsibilities

Invited or ad hoc Reviewers for the Following Journals:

1． Cell Metabolism (Cell press) (IF=22.415)

2． Chem (Cell press) (IF=18.205)

3． Cells (IF5.656)

4． Biochemical Journal (IF4.331)

5． Journal of Biological Chemistry (IF4.238)

6． Microbial Biotechnology (IF4.857)

7． Journal Of Cellular and Molecular Medicine (IF4.658)

8． Frontiers in Microbiology (IF=4.259)

9． Frontiers in Neuroscience (IF3.648)

10． International Journal of Molecular Sciences (IF=4.556)

11． Frontiers in Physiology (IF=4.134)

12． Journal of Cellular Physiology (IF3.923)

13． Open Biology (Journal of the Royal Society) (IF3.89)

14． Microbiological Research (IF3.701)

15． Marine Drugs (IF4.379)

16． Journal of Cancer (IF3.182)

17． Enzyme and Microbial Technology (Elsevier) (IF2.932)

18． Toxics (IF=2.84)

19． Applied Microbiology and Biotechnology (Springer) (IF3.67)

20． ACS Omega (IF2.58)

21． Marine Biotechnology (Springer) (IF2.798)

22． Journal of Biotechnology (Elsevier) (IF3.163)

23． Journal of Pediatric Neurology (IF1.385)

24． Canadian Journal of Microbiology (Springer) (IF1.243)

25． Environmental Chemistry Toxicology

26． International Research Journal of Biotechnology (IRJOB)

27． Biotechnology and Molecular Biology Reviews

28． Abstracts Reviewer for Annual AAPS Conferences


Journal and book series Editorships and Editorial board membership

Organize review processes for submitted manuscripts, including identifying and inviting qualified reviewers, analyzing reviewers’ critiques, comments, and overall scores to make final fair justifications, setting criteria for acceptance, rejection, and revision.   

  1. Guest Editor, Frontiers in Microbiology (2019-2020);
  2. Guest Editor, BioMed Research International (2018-2019);
  3. Biochemistry Editor, WebmedCentral.com
  4. Associate Editor, Current Signal Transduction Therapy (2018-present);
  5. Associate Editor, Archives in Neurology & Neuroscience (2018-present);
  6. Associate Editor, Annals of Advanced Biomedical Sciences (2018-present);
  7. Clinical Science: Current Trends
  8. Biomedical Research: Current Trends (BRCT)
  9. Editorial Board Member: Global Journal of Pathology and Microbiology (GJPM)

 

Teaching

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)

Chemistry of Life (CSC1009)

Anatomical Sciences (CSC2009)

Academic tutor for BMBS year 1 and 3
Lecture provider
LSRC session provider
Dissertation supervisor for CSC4020 (Research Project)

Supervision / Group

Postgraduate researchers

  • A. Brown
  • Nur Farah Meor Azlan
  • L. Tillman

Alumni

  • C. Davis
  • A. Haley (A2I funded student)
  • J. Y. Lee
  • G. Stewart (A2I funded student)
  • Z. Wu (Senior Visiting Scientist)

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