EMAIL jhc30@cam.ac.uk

Department

School

Clinical Medicine

Institute

Cambridge Institute for Medical Research

Research Theme Lifelong Brain Development and Brain Ageing Beyond the Neuron

Research Focus

Keywords

Alzheimer's Disease

Neurodegeneration

Clinical Conditions

Alzheimer's disease

Parkinson's disease

Huntington's disease

Lewy body dementia

Equipment & Techniques

Protein purification

Cell culture

Confocal microscopy

Recombinant protein expression

Back

Dr Jonathan Clarke

University Position

Senior Research Associate

Interests

Discovery and development of compounds that are beneficial to the treatment of neurodegenerative disease

Key Publications

The rational design of ARUK2007145, a dual inhibitor of the α and γ isoforms of the lipid kinase phosphatidylinositol 5-phosphate 4-kinase (PI5P4K)

DOI: http://doi.org/10.1039/d3md00355h
Journal: RSC Med Chem
E-pub date: 18 Oct 2023
Authors: GG Aldred, TPC Rooney, HMG Willems, HK Boffey, C Green, D Winpenny, J Skidmore, JH Clarke, SP Andrews

Identification of ARUK2002821 as an isoform-selective PI5P4Kα inhibitor.

DOI: http://doi.org/10.1039/d3md00039g
Journal: RSC Med Chem
E-pub date: 25 May 2023
Authors: HMG Willems, S Edwards, HK Boffey, SJ Chawner, C Green, T Romero, D Winpenny, J Skidmore, JH Clarke, SP Andrews

The Identification of Potent, Selective, and Brain Penetrant PI5P4Kγ Inhibitors as In Vivo-Ready Tool Molecules.

DOI: http://doi.org/10.1021/acs.jmedchem.2c01693
Journal: J Med Chem
E-pub date: 12 Jan 2023
Authors: TPC Rooney, GG Aldred, HK Boffey, HMG Willems, S Edwards, SJ Chawner, DE Scott, C Green, D Winpenny, J Skidmore, JH Clarke, SP Andrews

Development of Selective Phosphatidylinositol 5-Phosphate 4-Kinase γ Inhibitors with a Non-ATP-competitive, Allosteric Binding Mode.

DOI: http://doi.org/10.1021/acs.jmedchem.1c01819
Journal: J Med Chem
E-pub date: 24 Feb 2022
Authors: HK Boffey, TPC Rooney, HMG Willems, S Edwards, C Green, T Howard, D Ogg, T Romero, DE Scott, D Winpenny, J Duce, J Skidmore, JH Clarke, SP Andrews

Systematic Investigation of the Permeability of Androgen Receptor PROTACs.

DOI: http://doi.org/10.1021/acsmedchemlett.0c00194
Journal: ACS Med Chem Lett
E-pub date: 13 Aug 2020
Authors: DE Scott, TPC Rooney, ED Bayle, T Mirza, HMG Willems, JH Clarke, SP Andrews, J Skidmore

Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein.

DOI: http://doi.org/10.7554/eLife.29123
Journal: Elife
E-pub date: 26 Dec 2017
Authors: I Al-Ramahi, SSP Giridharan, Y-C Chen, S Patnaik, N Safren, J Hasegawa, M de Haro, AK Wagner Gee, SA Titus, H Jeong, J Clarke, D Krainc, W Zheng, RF Irvine, S Barmada, M Ferrer, N Southall, LS Weisman, J Botas, JJ Marugan

The function of phosphatidylinositol 5-phosphate 4-kinase γ (PI5P4Kγ) explored using a specific inhibitor that targets the PI5P-binding site.

DOI: http://doi.org/10.1042/BJ20141333
Journal: Biochem J
E-pub date: 1 Mar 2015
Authors: JH Clarke, M-L Giudici, JE Burke, RL Williams, DJ Maloney, J Marugan, RF Irvine

Evolutionarily conserved structural changes in phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) isoforms are responsible for differences in enzyme activity and localization.

DOI: http://doi.org/10.1042/BJ20130488
Journal: Biochem J
E-pub date: 15 Aug 2013
Authors: JH Clarke, RF Irvine

Publications

In B cells, phosphatidylinositol 5-phosphate 4-kinase-α synthesizes PI(4,5)P2 to impact mTORC2 and Akt signaling.

DOI: http://doi.org/10.1073/pnas.1522478113
Journal: Proc Natl Acad Sci U S A
E-pub date: 20 Sep 2016
Authors: SJ Bulley, A Droubi, JH Clarke, KE Anderson, LR Stephens, PT Hawkins, RF Irvine

Nuclear localizations of phosphatidylinositol 5-phosphate 4-kinases α and β are dynamic and independently regulated during starvation-induced stress.

DOI: http://doi.org/10.1042/BCJ20160380
Journal: Biochem J
E-pub date: 15 Jul 2016
Authors: A Droubi, SJ Bulley, JH Clarke, RF Irvine

Phosphatidylinositol 5-phosphate 4-kinase γ (PI5P4Kγ), a lipid signalling enigma.

DOI: http://doi.org/10.1016/j.jbior.2015.11.007
Journal: Adv Biol Regul
E-pub date: 1 May 2016
Authors: M-L Giudici, JH Clarke, RF Irvine

PI(5)P regulates autophagosome biogenesis.

DOI: http://doi.org/10.1016/j.molcel.2014.12.007
Journal: Mol Cell
E-pub date: 22 Jan 2015
Authors: M Vicinanza, VI Korolchuk, A Ashkenazi, C Puri, FM Menzies, JH Clarke, DC Rubinsztein

Exploring phosphatidylinositol 5-phosphate 4-kinase function.

DOI: http://doi.org/10.1016/j.jbior.2014.09.007
Journal: Adv Biol Regul
E-pub date: 1 Jan 2015
Authors: SJ Bulley, JH Clarke, A Droubi, M-L Giudici, RF Irvine

Enzyme activity of the PIP4K2A gene product polymorphism that is implicated in schizophrenia.

DOI: http://doi.org/10.1007/s00213-013-3299-y
Journal: Psychopharmacology (Berl)
E-pub date: 1 Nov 2013
Authors: JH Clarke, RF Irvine

Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) regulates TOR signaling and cell growth during Drosophila development.

DOI: http://doi.org/10.1073/pnas.1219333110
Journal: Proc Natl Acad Sci U S A
E-pub date: 9 Apr 2013
Authors: A Gupta, S Toscano, D Trivedi, DR Jones, S Mathre, JH Clarke, N Divecha, P Raghu

The activity, evolution and association of phosphatidylinositol 5-phosphate 4-kinases.

DOI: http://doi.org/10.1016/j.advenzreg.2011.09.002
Journal: Adv Biol Regul
E-pub date: 1 Jan 2012
Authors: JH Clarke, RF Irvine

Genomic tagging reveals a random association of endogenous PtdIns5P 4-kinases IIalpha and IIbeta and a partial nuclear localization of the IIalpha isoform.

DOI: http://doi.org/10.1042/BJ20100340
Journal: Biochem J
E-pub date: 1 Sep 2010
Authors: M Wang, NJ Bond, AJ Letcher, JP Richardson, KS Lilley, RF Irvine, JH Clarke

Localization, regulation and function of type II phosphatidylinositol 5-phosphate 4-kinases.

DOI: http://doi.org/10.1016/j.advenzreg.2009.10.006
Journal: Adv Enzyme Regul
E-pub date: 1 Aug 2010
Authors: JH Clarke, M Wang, RF Irvine

Distribution and neuronal expression of phosphatidylinositol phosphate kinase IIgamma in the mouse brain.

DOI: http://doi.org/10.1002/cne.22161
Journal: J Comp Neurol
E-pub date: 20 Nov 2009
Authors: JH Clarke, PC Emson, RF Irvine

Localization of phosphatidylinositol phosphate kinase IIgamma in kidney to a membrane trafficking compartment within specialized cells of the nephron.

DOI: http://doi.org/10.1152/ajprenal.90310.2008
Journal: Am J Physiol Renal Physiol
E-pub date: 1 Nov 2008
Authors: JH Clarke, PC Emson, RF Irvine

Type II PtdInsP kinases: location, regulation and function.

DOI: http://doi.org/10.1042/BSS0740149
Journal: Biochem Soc Symp
E-pub date: 1 Aug 2007
Authors: JH Clarke, JP Richardson, KA Hinchliffe, RF Irvine

Genomic tagging of endogenous type IIbeta phosphatidylinositol 5-phosphate 4-kinase in DT40 cells reveals a nuclear localisation.

DOI: http://doi.org/10.1016/j.cellsig.2007.01.010
Journal: Cell Signal
E-pub date: 1 Jun 2007
Authors: JP Richardson, M Wang, JH Clarke, KJ Patel, RF Irvine

Effects of lipid kinase expression and cellular stimuli on phosphatidylinositol 5-phosphate levels in mammalian cell lines.

DOI: http://doi.org/10.1016/j.febslet.2005.04.027
Journal: FEBS Lett
E-pub date: 23 May 2005
Authors: HF Roberts, JH Clarke, AJ Letcher, RF Irvine, KA Hinchliffe