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Dr Patrick Lewis
Appointments:Senior Research Associate, Molecular Neuroscience, Institute of Neurology
I studied biochemistry at the University of Manchester, undertaking a year of research at the Mayo Clinic in Florida as part of this during which I investigated cellular dysfunction linked to mutations in the amyloid precursor protein and presenilin 1 associated with familial Alzheimer's disease. I then moved to the MRC Prion Unit at UCL, where I carried out graduate studies into the molecular mechanisms of scrapie gaining my PhD in 2005. From 2005 to 2007 I was visiting fellow in the Laboratory of Neurogenetics at the National Institute of Aging in Bethesda, mentored by Mark Cookson. It was here that I first started working on LRRK2, a protein which has been the object of my affections ever since. I returned to UCL in 2007 as a Brain Research Trust senior research fellow in the Department of Molecular Neuroscience and have continued my research into the basis of Parkinson's disease linked to mutations in LRRK2. I am currently a Parkinson's UK research fellow.
My research concentrates on characterizing the biological insults leading to cell death in inherited forms of Parkinsonism linked to mutations in LRRK2. We are using a range of experimental approaches to examine the impact of mutations both on the biochemistry of these proteins, their folding and activities, and on the cell biology of neuronal cells. Our aim is to generate a comprehensive overview of the structure/function/phenotype of LRRK2, linking this in to the pathologies observed in patients.
Techniques used include cell and primary culture, kinase and GTPase analysis, circular dichroism spectropolarimetery, analytical ultracentrifugation.
- Identification of new components in Parkinson's Disease signalling pathways
- Neurological disease
Displaying 29 most recent publications. For the full list please visit UCL Discovery
- Kiely AP,Asi YT,Kara E,Limousin P,Ling H,Lewis P,Proukakis C,Quinn N,Lees AJ,Hardy J,Revesz T,Houlden H,Holton JL (2013) α-Synucleinopathy associated with G51D SNCA mutation: a link between Parkinson's disease and multiple system atrophy? Acta Neuropathologica, 1 - 17.
- Lewis PA,Cookson MR (2012) Gene expression in the Parkinson's disease brain. Brain Res Bull, 88(4), 302 - 312. 10.1016/j.brainresbull.2011.11.016.
- Lewis PA,Alessi DR (2012) Deciphering the function of leucine-rich repeat kinase 2 and targeting its dysfunction in disease. Biochem Soc Trans, 40(5), 1039 - 1041. 10.1042/BST20120178.
- Jebelli JD,Dihanich S,Civiero L,Manzoni C,Greggio E,Lewis PA (2012) GTP binding and intramolecular regulation by the ROC domain of Death Associated Protein Kinase 1. Sci Rep, 2, 695. 10.1038/srep00695.
- Wray S,Self M,NINDS Parkinson's Disease iPSC Consortium ,NINDS Huntington's Disease iPSC Consortium ,NINDS ALS iPSC Consortium ,Lewis PA,Taanman JW,Ryan NS,Mahoney CJ,Liang Y,Devine MJ,Sheerin UM,Houlden H,Morris HR,Healy D,Marti-Masso JF,Preza E,Barker S,Sutherland M,Corriveau RA,D'Andrea M,Schapira AH,Uitti RJ,Guttman M,Opala G,Jasinska-Myga B,Puschmann A,Nilsson C,Espay AJ,Slawek J,Gutmann L,Boeve BF,Boylan K,Stoessl AJ,Ross OA,Maragakis NJ,Van Gerpen J,Gerstenhaber M,Gwinn K,Dawson TM,Isacson O,Marder KS,Clark LN,Przedborski SE,Finkbeiner S,Rothstein JD,Wszolek ZK,Rossor MN,Hardy J (2012) Creation of an open-access, mutation-defined fibroblast resource for neurological disease research. PLoS One, 7(8), e43099. 10.1371/journal.pone.0043099.
- Patani R,Lewis PA,Trabzuni D,Puddifoot CA,Wyllie DJ,Walker R,Smith C,Hardingham GE,Weale M,Hardy J,Chandran S,Ryten M (2012) Investigating the utility of human embryonic stem cell-derived neurons to model ageing and neurodegenerative disease using whole-genome gene expression and splicing analysis. J Neurochem, 122(4), 738 - 751. 10.1111/j.1471-4159.2012.07825.x.
- Lewis PA (2012) Assaying the kinase activity of LRRK2 in vitro. J Vis Exp(59). 10.3791/3495.
- Lewis PA,Manzoni C (2012) LRRK2 and human disease: a complicated question or a question of complexes? Sci Signal, 5(207), pe2. 10.1126/scisignal.2002680.
- Devine MJ,Ryten M,Vodicka P,Thomson AJ,Burdon T,Houlden H,Cavaleri F,Nagano M,Drummond NJ,Taanman JW,Schapira AH,Gwinn K,Hardy J,Lewis PA,Kunath T (2011) Parkinson's disease induced pluripotent stem cells with triplication of the α-synuclein locus. Nat Commun, 2, 440. 10.1038/ncomms1453.
- Devine MJ,Kaganovich A,Ryten M,Mamais A,Trabzuni D,Manzoni C,McGoldrick P,Chan D,Dillman A,Zerle J,Horan S,Taanman JW,Hardy J,Marti-Masso JF,Healy D,Schapira AH,Wolozin B,Bandopadhyay R,Cookson MR,van der Brug MP,Lewis PA (2011) Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue. PLoS One, 6(7), e22489. 10.1371/journal.pone.0022489.
- Plun-Favreau H,Lewis PA,Hardy J,Martins LM,Wood NW (2010) Cancer and Neurodegeneration: Between the Devil and the Deep Blue Sea PLOS GENET, 6(12). 10.1371/journal.pgen.1001257.
- Wray S,Lewis PA (2010) A tangled web - tau and sporadic Parkinson's disease. Front Psychiatry, 1, 150. 10.3389/fpsyt.2010.00150.
- Hardy J,Lewis P,Revesz T,Lees A,Paisan-Ruiz C (2009) The genetics of Parkinson's syndromes: a critical review Current Opinion in Genetics and Development, 19(3), 254 - 265. 10.1016/j.gde.2009.03.008.
- Li YC,Dunn L,Greggio E,Krumm B,Jackson GS,Cookson MR,Lewis PA,Deng JP (2009) The R1441C mutation alters the folding properties of the ROC domain of LRRK2 BBA-MOL BASIS DIS, 1792(12), 1194 - 1197. 10.1016/j.bbadis.2009.09.010.
- Lewis PA (2009) The function of ROCO proteins in health and disease Biology of the Cell, 101(3), 183 - 191. 10.1042/BC20080053.
- Lewis PA (2008) Emerging pathways in genetic Parkinson's disease The FEBS Journal, 275(23), 5747 - 5747. 10.1111/j.1742-4658.2008.06706.x.
- Devine MJ,Lewis PA (2008) Emerging pathways in genetic Parkinson's disease: tangles, Lewy bodies and LRRK2 The FEBS Journal, 275(23), 5748 - 5757. 10.1111/j.1742-4658.2008.06707.x.
- Cookson MR,Hardy J,Lewis PA (2008) Genetic Neuropathology of Parkinson's Disease INT J CLIN EXP PATHO, 1(3), 217 - 231.
- Deng JP,Lewis PA,Greggio E,Sluch E,Beilina A,Cookson MR (2008) Structure of the ROC domain from the Parkinson's disease-associated leucine-rich repeat kinase 2 reveals a dimeric GTPase P NATL ACAD SCI USA, 105(5), 1499 - 1504. 10.1073/pnas.0709098105.
- Greggio E,Lewis PA,van der Brug MP,Ahmad R,Kaganovich A,Ding JH,Beilina A,Baker AK,Cookson MR (2007) Mutations in LRRK2/dardarin associated with Parkinson disease are more toxic than equivalent mutations in the homologous kinase LRRK1 J NEUROCHEM, 102(1), 93 - 102. 10.1111/j.1471-4159.2007.04523.x.
- Greggio E,Jain S,Kingsbury AE,Bandopadhyay R,Kaganovich A,Lewis P,van der Brug MP,Beilina A,Blackinton J,Thomas KJ,Ahmad R,Miller DW,Lees A,Harvey RJ,Harvey K,Cookson MR (2006) Kinase activity is required for dominant effects of mutant dardarin. Neurobiology of Disease, 23, 329 - 341. 10.1016/j.nbd.2006.04.001.
- Lewis PA,Tattum MH,Jones S,Bhelt D,Batchelor M,Clarke AR,Collinge J,Jackson GS (2006) Codon 129 polymorphism of the human prion protein influences the kinetics of amyloid formation Journal of General Virology, 87(8), 2443 - 2449.
- Lewis PA,Properzi F,Prodromidou K,Clarke AR,Collinge J,Jackson GS (2006) Removal of the glycosylphosphatidylinositol anchor from PrPSc by cathepsin D does not reduce prion infectivity Biochemical Journal, 395(2), 443 - 448.
- Amtul Z,Lewis PA,Piper S,Crook R,Baker M,Findlay K,Singleton A,Hogg M,Younkin L,Younkin SG,Hardy J,Hutton M,Boeve BF,Tang-Wai D,Golde TE (2002) A presenilin 1 mutation associated with familial frontotemporal dementia inhibits gamma-secretase cleavage of APP and notch. Neurobiol Dis, 9(2), 269 - 273. 10.1006/nbdi.2001.0473.
- Lewis PA,Piper S,Baker M,Onstead L,Murphy MP,Hardy J,Wang R,McGowan E,Golde TE (2001) Expression of BRI-amyloid beta peptide fusion proteins: a novel method for specific high-level expression of amyloid beta peptides. Biochim Biophys Acta, 1537(1), 58 - 62.
- Lewis PA,Perez-Tur J,Golde TE,Hardy J (2000) The presenilin 1 C92S mutation increases abeta 42 production. Biochem Biophys Res Commun, 277(1), 261 - 263. 10.1006/bbrc.2000.3646.
- Houlden H,Baker MD,McGowan E,Lewis P,Hutton M,Crook R,Wood NW,Kumar-Singh S,Geddes J,Swash M,Scaravilli F,Holton JL,Lashley T,Tomita T,Hashimoto T,Verkkoniemi A,Kalimo H,Somer M,Paetau A,Martin JJ,Van Broeckhoven C,Golde T,Hardy J,Haltia M,Revesz T (2000) Variant Alzheimer's disease with spastic paraparesis and cotton wool plaques is caused by PS-1 mutations that lead to exceptionally high amyloid-beta concentrations Annals of Neurology, 48(5), 806 - 808.
- McLendon C,Xin T,Ziani-Cherif C,Murphy MP,Findlay KA,Lewis PA,Pinnix I,Sambamurti K,Wang R,Fauq A,Golde TE (2000) Cell-free assays for gamma-secretase activity. FASEB J, 14(15), 2383 - 2386. 10.1096/fj.00-0286fje.
- Murphy MP,Uljon SN,Fraser PE,Fauq A,Lookingbill HA,Findlay KA,Smith TE,Lewis PA,McLendon DC,Wang R,Golde TE (2000) Presenilin 1 regulates pharmacologically distinct gamma -secretase activities. Implications for the role of presenilin in gamma -secretase cleavage. J Biol Chem, 275(34), 26277 - 26284. 10.1074/jbc.M002812200.
BiographyI studied biochemistry at the University of Manchester, undertaking a year of research at the Mayo Clinic in Florida as part of this during which I investigated cellular dysfunction linked to mutations in the amyloid precursor protein and presenilin 1 associated with familial Alzheimer's disease. I then moved to the MRC Prion Unit at UCL, where I carried out graduate studies into the molecular mechanisms of scrapie gaining my PhD in 2005. From 2005 to 2007 I was visiting fellow in the Laboratory of Neurogenetics at the National Institute of Aging in Bethesda, mentored by Mark Cookson. It was here that I first started working on LRRK2, a protein which has been the object of my affections ever since. I returned to UCL in 2007 as a Brain Research Trust senior research fellow in the Department of Molecular Neuroscience and have continued my research into the basis of Parkinson's disease linked to mutations in LRRK2. I am currently a Parkinson's UK research fellow.
- 2005: Doctor of Philosophy, University College London
- 2001: Bachelor of Science, University of Manchester
- 03-05: Certificate in Learning and Teaching in HE Part 2, University College London
- 03-0: Certificate in Learning and Teaching in HE Part 1, University College London