Peter Scott McPherson, PhD
Peter S. McPherson (PhD, FRSC), is a Distinguished James McGill Professor of Neurology and Neurosurgery and Anatomy and Cell Biology at The Neuro where he is a member of the Neurodegenerative Disease Research Group. He is also a Fellow of the Royal Society of Canada. The McPherson laboratory uses biochemical, molecular, structural, genetic and cellular approaches to identify and functionally characterize proteins that operate in protein trafficking in the endo/lysosomal system. Alterations in these cellular pathways lead to diseases including brain tumors and neurodevelopmental and neurodegenerative disorders. Current projects in the lab reveal how disruption in transport of selective cargo from endosomes to the cell surface contributes to the development of glioblastoma, a neurodevelopmental disorder called DENND5A-mediated epileptic encephalopathy, and Parkinson's disease and ALS. Understanding the cell biological basis of neurological disease is a major focus of the laboratory.
McPherson has also led, along with Research Scientist Carl Laflamme, an initiative called YCharOS (antibody characterization through open science) that teams with 14 major antibody manufacturers and knockout cell line providers to validate commercial antibodies against target proteins selected by funders. All data is rapidly transmitted to open sources (YCharOS and Zenodo) as part of a public good.
Modeling Parkinson's disease pathology in human dopaminergic neurons by sequential exposure to α-synuclein fibrils and proinflammatory cytokines. (2024) Bayati A, Ayoubi R, Aguila A, Zorca CE, Deyab G, Han C, Recinto SJ, Nguyen-Renou E, Rocha C, Maussion G, Luo W, Shlaifer I, Banks E, McDowell I, Del Cid Pellitero E, Ding XE, Sharif B, Séguéla P, Yaqubi M, Chen CX, You Z, Abdian N, McBride HM, Fon EA, Stratton JA, Durcan TM, Nahirney PC, McPherson PS. Nat Neurosci. doi: 10.1038/s41593-024-01775-4. PMID: 39379564
Alpha-synuclein, autophagy-lysosomal pathway, and Lewy bodies: Mutations, propagation, aggregation, and the formation of inclusions. (2024) Bayati A, McPherson PS. J Biol Chem. doi: 10.1016/j.jbc.2024.107742. PMID: 39233232
Loss of symmetric cell division of apical neural progenitors drives DENND5A-related developmental and epileptic encephalopathy. (2024) Banks E, Francis V, Lin SJ, Kharfallah F, Fonov V, Lévesque M, Han C, Kulasekaran G, Tuznik M, Bayati A, Al-Khater R, Alkuraya FS, Argyriou L, Babaei M, Bahlo M, Bakhshoodeh B, Barr E, Bartik L, Bassiony M, Bertrand M, Braun D, Buchert R, Budetta M, Cadieux-Dion M, Calame DG, Cope H, Cushing D, Efthymiou S, Elmaksoud MA, El Said HG, Froukh T, Gill HK, Gleeson JG, Gogoll L, Goh ES, Gowda VK, Haack TB, Hashem MO, Hauser S, Hoffman TL, Hogue JS, Hosokawa A, Houlden H, Huang K, Huynh S, Karimiani EG, Kaulfuß S, Korenke GC, Kritzer A, Lee H, Lupski JR, Marco EJ, McWalter K, Minassian A, Minassian BA, Murphy D, Neira-Fresneda J, Northrup H, Nyaga DM, Oehl-Jaschkowitz B, Osmond M, Person R, Pehlivan D, Petree C, Sadleir LG, Saunders C, Schoels L, Shashi V, Spillmann RC, Srinivasan VM, Torbati PN, Tos T; Undiagnosed Diseases Network; Zaki MS, Zhou D, Zweier C, Trempe JF, Durcan TM, Gan-Or Z, Avoli M, Alves C, Varshney GK, Maroofian R, Rudko DA, McPherson PS. Nat Commun. doi: 10.1038/s41467-024-51310-z. PMID: 39174524
A neurodevelopmental disorder associated with a loss-of-function missense mutation in RAB35. (2024) Aguila A, Salah S, Kulasekaran G, Shweiki M, Shaul-Lotan N, Mor-Shaked H, Daana M, Harel T, McPherson PS. J Biol Chem. doi: 10.1016/j.jbc.2024.107124. PMID: 38432637
DENND6A links Arl8b to a Rab34/RILP/dynein complex, regulating lysosomal positioning and autophagy. (2024) Kumar R, Khan M, Francis V, Aguila A, Kulasekaran G, Banks E, McPherson PS. Nat Commun. doi: 10.1038/s41467-024-44957-1. PMID: 38296963
Heed a decade of calls for antibody validation. (2023) Kahn RA, Virk HS, McPherson PS. Nature. doi: 10.1038/d41586-023-02566-w. PMID: 37582877
DENND2B activates Rab35 at the intercellular bridge, regulating cytokinetic abscission and tetraploidy. (2023) Kumar R, Francis V, Ioannou MS, Aguila A, Khan M, Banks E, Kulasekaran G, McPherson PS. Cell Rep. 2023 doi: 10.1016/j.celrep.2023.112795. PMID: 37454296
Scaling of an antibody validation procedure enables quantification of antibody performance in major research applications. (2023) Ayoubi R, Ryan J, Biddle MS, Alshafie W, Fotouhi M, Bolivar SG, Moleon VR, Eckmann P, Worrall D, McDowell I, Southern K, Reintsch W, Durcan TM, Brown CM, Bandrowski A, Virk HS, Edwards AM, McPherson PS, Laflamme C. Elife. 2023 Nov 23;12:RP91645. doi: 10.7554/eLife.91645 PMID: 37398479
A cell-based GEF assay reveals new substrates for DENN domains and a role for DENND2B in primary ciliogenesis. (2023) Kumar R, Francis V, Kulasekaran G, Khan M, Armstrong GAB, McPherson PS. Sci Adv. doi: 10.1126/sciadv.abk3088. PMID: 35196081
SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis. (2021) Bayati A, Kumar R, Francis V, McPherson PS. J Biol Chem. doi: 10.1016/j.jbc.2021.100306. PMID: 33476648
An Arf/Rab cascade controls the growth and invasiveness of glioblastoma. (2021) Kulasekaran G, Chaineau M, Piscopo VEC, Verginelli F, Fotouhi M, Girard M, Tang Y, Dali R, Lo R, Stifani S, McPherson PS. J Cell Biol. 2021 Feb 1;220(2):e202004229. doi: 10.1083/jcb.202004229. PMID: 33443570 Free PMC article.
Ioannou, M.S., Bell, E.S., Girard, M., Chaineau, M., Hamlin, J.N.R., Daubaras, M., Monast, A., Park, M., Hodgson, L., and McPherson, P.S. (2015) DENND2B activates Rab13 at the leading edge of migrating cells and promotes metastatic behavior. J. Cell Biol. 208: 629-648. (Featured in a JCB Podcast called biobytes, in which the journal highlights one significant paper appearing in each issue. A movie from this manuscript, imaging Rab13 activation at the leading edge of a migrating cell, was posted by the Journal on their Facebook page and received > 34,000 views. Featured in the Faculty of 1000).
Girard, M., Larivière, R., Parfitt, D.A., Deane, E.C., Gaudet, R., Nossova, N., Blondeau, F., Prenosil, G., Vermeulen, E.G.M., Duchen, M.R., Richter, A., Shoubridge, E.A., Gehring, K., McKinney, R.A., Brais, B., Chapple, J.P. and McPherson, P.S. (2012) Mitochondrial dysfunction and Purkinje cell loss in Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS). Proc. Natl. Acad. Sci., USA 109: 1661-1666. (Selected as Novel and Newsworthy when presented at the American Society for Cell Biology, December 2011, coverage in multiple newspapers including a full-page feature in the Globe & Mail, reported by multiple radio and TV stations, subject of a Nature News and Views, Narenda, D.P. and Youle, R.J. (2012) Neurodegeneration: Trouble in the cell's powerhouse, Nature, 483: 418-419).
Allaire, P.D., Marat, A.L., Dall'Armi, C., Di Paolo, G., McPherson, P.S.*, and Ritter, B*. (2010) The connecdenn DENN domain: A GEF for Rab35 mediating cargo-specific exit from early endosomes. Mol. Cell. 37: 370-382. *=co-corresponding author.
Blondeau, F., Ritter, B., Allaire, P.D., Wasiak, S., Girard, M., Hussain, N.K., Angers, A., Legendre-Guillemin, V., Roy, L., Boismenu, D., Kearney, R.E., Bell, A.W., Bergeron, J.J.M., and McPherson, P.S. (2004) Tandem mass spectrometry analysis of brain clathrin-coated vesicles reveals their critical involvement in synaptic vesicle recycling. Proc. Natl. Acad. Sci., USA 101:3833-3838. (selected by the Faculty of 1000)
Hussain, N.K., Jenna, S., Glogauer, M., Quinn, C.C., Wasiak, S., Kay, B.K., Stossel, T.P., Lamarche-Vane, N., and McPherson, P.S. (2001) The endocytic protein intersectin-l regulates actin assembly via Cdc42 and N-WASP. Nat. Cell Biol. 3:927-932.
