Latest published work

Generation of human midbrain organoids

In collaboration with Dr. Durcan's team, we developed a protocol to successfully differentiate human induced pluripotent stem cells into 3 dimensional midbrain organoids

 

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Investigating the complexity of MDV cargoes

Mitochondrial-derived vesicles (MDVs) are implicated in mitochondrial quality control, a mechanism likely involved in PD. The diversity and composition of MDVs are still to unravel. Our study aimed at identifying the cargo in brain MDVs.

 

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Unraveling the landscape of Parkin variants

Mutations in Parkin are the most common cause of early-onset PD, but many variants of the protein exist. In this study, we developed a framework to classify Parkin variants' pathogenicity based on the integration of clinical data and functional evidence.

 

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Deepening our understanding of SMPD1 mutations in PD

SMPD1 (acid-sphingomyelinase) variants have been associated with Parkinson’s disease. In this collaborative work, SMPD1 mutations were studied using genetic, proteomic and cellular approches

 

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Exploring the function of mitochondria-ER contact sites

Mitochondria-ER contact sites are largely understudied. Here we investigated their role in mitochondrial quality control pathways

 

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Publications

Selected Publications 

Del Cid-Pellitero E, Tavassoly O, Larroquette F, Cai E, Thomas RA, Soubannier V, Luo W, Durcan TM, Fon EA. Pharmacological Inhibition of Brain EGFR Activation By a BBB-penetrating Inhibitor, AZD3759, Attenuates α-synuclein Pathology in a Mouse Model of α-Synuclein Propagation. Neurotherapeutics 2021 [Read the paper]


Del Cid-Pellitero E, Jin JW, Fan X, Liu XX, Zhou L, Dai C, Gibbs E, He W, Li H, Wu X, Hill A, Leavitt BR, Cashman N, Liu L, Lu J, Durcan TM, Dong Z, Fon EA & Wang YT. Development of an α-synuclein knockdown peptide and evaluation of its efficacy in Parkinson’s disease models. Communications Biology 2021 [Read the paper]


Roberts R., Bayne AN., Goiran T., Lévesque D., Boisvert FM., Trempe JF., Fon EA. Proteomic Profiling of Mitochondrial-Derived Vesicles in Brain Reveals Enrichment of Respiratory Complex Sub-assemblies and Small TIM Chaperones. J Proteome Res  2021 [Read the paper]


Jefri M, Bell S, Peng H, Hettige N, Maussion G, Soubannier V, Wu H, Silveira H, Theroux JF, Moquin L, Zhang X, Aouabed Z, Krishnan J, O'Leary LA, Antonyan L, Zhang Y, McCarty V, Mechawar N, Gratton A, Schuppert A, Durcan TM, Fon EA, Ernst C. Stimulation of L-type calcium channels increases tyrosine hydroxylase and dopamine in ventral midbrain cells induced from somatic cells. Stem Cells Transl Med. 2020 [Read the paper]


Martínez GF, Gazal NG, Quassollo G, Szalai AM, Cid-Pellitero ED, Durcan TM, Fon EA, Bisbal M, Stefani FD, Unsain N. Quantitative expansion microscopy for the characterization of the spectrin periodic skeleton of axons using fluorescence microscopy. Sci. Rep. 2020;10(1):2917. [Read the paper]


Gan-Or Z, Rao T, Leveille E, Degroot C, Chouinard S, Cicchetti F, Dagher A, Das S, Desautels A, Drouin-Ouellet J, Durcan T, Gagnon JF, Genge A, Karamchandani J, Lafontaine AL, Sun SLW, Langlois M, Levesque M, Melmed C, Panisset M, Parent M, Poline JB, Postuma RB, Pourcher E, Rouleau GA, Sharp M, Monchi O, Dupré N, Fon EA. The Quebec Parkinson Network: A Researcher-Patient Matching Platform and Multimodal Biorepository. J Parkinsons Dis. 2020;10(1):301-313 [Read the paper]


Eldeeb MA, MacDougall EJ, Ragheb MA, Fon EA. Beyond ER: Regulating TOM-Complex-Mediated Import by Ubx2. Trends Cell Biol. 2019;29(9):687-689 [Read the paper]


Fava VM, Xu YZ, Lettre G, Van Thuc N, Orlova M, Thai VH, Tao S, Croteau N, Eldeeb MA, MacDougall EJ, Cambri G, Lahiri R, Adams L, Fon EA, Trempe JF, Cobat A, Alcaïs A, Abel L, Schurr E. Pleiotropic effects for Parkin and LRRK2 in leprosy type-1 reactions and Parkinson's disease. Proc Natl Acad Sci U S A. 2019;116(31):15616-15624 [Read the paper]


Eldeeb MA, Ragheb MA, Fon EA. Cell Death: N-degrons Fine-Tune Pyroptotic Cell Demise. Curr Biol. 2019;29(12):R588-R591 [Read the paper]


Eldeeb MA, Fahlman RP, Esmaili M, Fon EA. When Degradation Elicits the Alarm: N-Terminal Degradation of NLRP1B Unleashes Its Inflammasome Activity. Mol Cell. 2019;74(4):637-639 [Read the paper]


Yi W, MacDougall EJ, Tang MY, Krahn AI, Gan-Or Z, Trempe JF, Fon EA. The landscape of Parkin variants reveals pathogenic mechanisms and therapeutic targets in Parkinson's disease. Hum Mol Genet. 2019;28(17):2811-2825 [Read the paper]


Alcalay RN, Mallett V, Vanderperre B, Tavassoly O, Dauvilliers Y, Wu RYJ, Ruskey JA, Leblond CS, Ambalavanan A, Laurent SB, Spiegelman D, Dionne-Laporte A, Liong C, Levy OA, Fahn S, Waters C, Kuo SH, Chung WK, Ford B, Marder KS, Kang UJ, Hassin-Baer S, Greenbaum L, Trempe JF, Wolf P, Oliva P, Zhang XK, Clark LN, Langlois M, Dion PA, Fon EA, Dupre N, Rouleau GA, Gan-Or Z. SMPD1 mutations, activity, and α-synuclein accumulation in Parkinson's disease. Mov Disord. 2019;34(4):526-535 [Read the paper]


Mohamed NV, Mathur M, Da Silva RV, Beitel LK, Fon EA, Durcan TM. Generation of human midbrain organoids from induced pluripotent stem cells. MNI Open Research 2019 [Read the paper]


Mohamed NV, Larroquette F, Beitel LK, Fon EA, Durcan TM. One Step Into the Future: New iPSC Tools to Advance Research in Parkinson's Disease and Neurological Disorders. J Parkinsons Dis. 2019;9(2):265-281 [Read the paper]


Eldeeb MA*, Fahlman RP, Esmalili M, Fon EA. Formylation of Eukaryotic Cytoplasmic Proteins:Linking Stress to Degradation. Trends Biochem, Sci. 2019; 181-183 [Read the paper]


Rudakou U, Ouled Amar Bencheikh B, Ruskey JA, Krohn L, Laurent SB, Spiegelman D, Liong C, Fahn S, Waters C, Monchi O, Fon EA, Dauvilliers Y, Alcalay RN, Dupré N, Gan-Or Z. Common and rare GCH1 variants are associated with Parkinson's disease. Neurobiol. Aging. 2019; 73:231.e1-231.e6. [Read the paper]


McLelland GL*, Fon EA. MFN2 retrotranslocation boosts mitophagy by uncoupling mitochondria from the ER. Autophagy. 2018; 1658-1660. [Read the paper]


McLelland GL*, Fon EA. Principles of mitochondrial vesicle transport. Curr. Opin. Physiol. 2018; 3:25–33. [Read the paper]


Ouled Amar Bencheikh B, Leveille E, Ruskey JA, Spiegelman D, Liong C, Fon EA, Rouleau GA, Dauvilliers Y, Dupre N, Alcalay RN, Gan-Or Z. Sequencing of the GBA coactivator, Saposin C, in Parkinson disease. Neurobiol. Aging. 2018; S0197-4580(18)30239-2.–33. [Read the paper]


Ruskey JA, Zhou S, Santiago R, Franche LA, Alam A, Roncière L, Spiegelman D, Fon EA, Trempe JF, Kalia LV, Postuma RB, Dupre N, Rivard GE, Assouline S, Amato D, Gan-Or Z. The GBA p.Trp378Gly mutation is a probable French-Canadian founder mutation causing Gaucher disease and synucleinopathies.  Clin. Genet. 2018; [Read the paper]


Bell S, Maussion G, Jefri M, Peng H, Theroux JF, Silveira H, Soubannier V, Wu H, Hu P, Galat E, Torres-Platas SG, Boudreau-Pinsonneault C, O'Leary LA, Galat V, Turecki G, Durcan TM, Fon EA, Mechawar N, Ernst C. Disruption of GRIN2B Impairs Differentiation in Human Neurons. Stem Cell Reports. 2018; S2213-6711(18)30236-4 [Read the paper]


Li J, Ruskey JA, Arnulf I, Dauvilliers Y, Hu MTM, Högl B, Leblond CS, Zhou S, Ambalavanan A, Ross JP, Bourassa CV, Spiegelman D, Laurent SB, Stefani A, Charley Monaca C, Cochen De Cock V, Boivin M, Ferini-Strambi L, Plazzi G, Antelmi E, Young P, Heidbreder A, Labbe C, Ferman TJ, Dion PA, Fan D, Desautels A, Gagnon JF, Dupré N, Fon EA, Montplaisir JY, Boeve BF, Postuma RB, Rouleau GA, Ross OA and Gan-Or Z. Full sequencing and haplotype analysis of MAPT in Parkinson disease and REM sleep behavior disorder. Mov. Disord. 2018; [Read the paper]


McLelland GL*, Goiran T*, Yi W*, Dorval G, Chen CX, Lauinger ND*, Krahn AI*, Valimehr S, Rakovic A, Rouiller I, Durcan TM, Trempe JF, Fon EA. Mfn2 ubiquitination by PINK1/parkin gates the p97-dependent release of ER from mitochondria to drive mitophagy. Elife. 2018; 7.pii: e32866. [Read the paper]


Mohtashami S, He Q, Ruskey JA, Zhou S, Dion PA, Allen RP, Earley CJ, Fon EA, Xiong L, Dupre N, Dauvilliers Y, Rouleau GA, Gan-Or Z. TOX3 Variants Are Involved in Restless Legs Syndrome and Parkinson's Disease with Opposite Effects. J. Mol. Neurosci. 2018; 64(3):341-345. [Read the paper]


Ross JP, Mohtashami S, Leveille E, Johnson AM, Xiong L, Dion PA, Fon EA, Dauvilliers Y, Dupré N, Rouleau GA, Gan-Or Z. Association study of essential tremor genetic loci in Parkinson's disease. Neurobiol. Aging. 2018; 66:178.e13-178.e15. [Read the paper]


Manecka DL*, Vanderperre B*, Fon EA, Durcan TM. The Neuroprotective Role of Protein Quality Control in Halting the Development of Alpha-Synuclein Pathology. Front. Mol. Neurosci. 2017; 10: 311. [Read the paper]


Tang MY*, Vranas M, Krahn A*, Pundlik S*, Trempe JF, Fon EA. Structure-guided mutagenesis reveals a hierarchical mechanism of Parkin activation. Nat. Commun. 2017; 8: 14697. [Read the paper]


Rodriguez L, Mohamed NV, Desjardins A, Lippé R, Fon EA, Leclerc N. Rab7A regulates Tau secretion. J. Neurochem. 2017; 141(4):592-605. [Read the paper]


Roberts RF*, Fon EA. Presenting mitochondrial antigens: PINK1, Parkin and MDVs steal the show. Cell Res. 2016; 26(11):1180-1181. [Read the paper]


Roberts RF*, Tang MY*, Fon EA, Durcan TM. Defending the mitochondria: The pathways of mitophagy and mitochondrial-derived vesicles. Int. J. Biochem. Cell. Biol. 2016; 79:427-436. [Read the paper]


Munoz DP, Fon EA, Chen R. A New Collaboration Between the Canadian Association for Neuroscience and CJNS. Can. J. Neurol. Sci. 2016; 43(1):2. [Read the paper]


McLelland GL*, Lee SA*, McBride HM, Fon EA. Syntaxin-17 delivers PINK1/parkin-dependent mitochondrial vesicles to the endolysosomal system. J. Cell Biol. 2016; 214(3):275-91. [Read the paper]


Schreij AM, Fon EA, McPherson PS. Endocytic membrane trafficking and neurodegenerative disease. Cell. Mol. Life Sci. 2016; 73(8):1529-45. [Read the paper]


Durcan TM*, Fon EA. The three P’s of Mitophagy: PARKIN, PINK1 and Post-Translational Modifications. Genes Dev. 2015; 29(10):989-999. [Read the paper]


Ryan BJ, Hoek S, Fon EA, Wade-Martins R. Mitochondrial dysfunction and mitophagy in Parkinson's: from familial to sporadic disease. Trends Biochem. Sci. 2015; 40(4):200-210. [Read the paper]


Durcan TM*, Fon EA. USP8 and PARK2/parkin-mediated mitophagy. Autophagy. 2015; 11(2):428-9. [Read the paper]


Aguileta MA*, Korac J, Durcan TM*, Trempe JF*, Haber M*, Gehring K, Elsasser S, Waidmann O, Fon EA, Husnjak K. The E3 Ubiquitin ligase parkin is recruited to the 26S proteasome via the proteasomal ubiquitin receptor Rpn13. J Biol Chem. 2015; 290(12):7492-505. [Read the paper]


Bertolin G, Jacoupy M, Traver S, Ferrando-Miguel R, Saint Georges T, Grenier K*, Ardila-Osorio H, Muriel MP, Takahashi H, Lees AJ, Gautier C, Guedin D, Coge F, Fon EA, Brice A, Corti O. Parkin maintains mitochondrial levels of the protective Parkinson's disease-related enzyme 17-β hydroxysteroid dehydrogenase type 10. Cell Death Differ. 2015; 22(10):1563-76. [Read the paper]


Schreij AMA*, Chaineau M, Ruan W, Lin S, Barker, PA, Fon EA§, McPherson PS§. LRRK2 localizes to endosomes and interacts with clathrin-light chains to limit Rac1 activation. EMBO Rep. 2015; 16(1):79-86. §co-corresponding authors [Read the paper]


Grenier K*, Kontogiannea M*, Fon EA. Short mitochondrial ARF triggers Parkin/PINK1-dependent mitophagy in neurons. J. Biol. Chem. 2014; 289(43):29519-30 [Read the paper]


Durcan TM*, Tang MY*, Pérusse JR, Dashti EA*, Aguileta MA*, McLelland GL*, Gros P*, Shaler TA, Faubert D, Coulombe B, Fon EA. USP8 Regulates Mitophagy by Removing K6-linked Ubiquitin Conjugates from Parkin. EMBO J. 2014; 33(21):2473-91 [Read the paper]


Sugiura A, McLelland GL*, Fon EA, McBride HM. A new Pathway for Mitochondrial Quality Control: Mitochondrial Derived Vesicles. EMBO J. 2014; 33(19):2142-2156 [Read the paper]


Koyano F, Okatsu K, Kosako H, Tamura Y, Go E, Kimura M, Kimura Y, Tsuchiya H, Yoshihara H, Hirokawa T, Endo T, Fon EA, Trempe JF, Saeki Y, Tanaka K, Matsuda N. Ubiquitin is phosphorylated by PINK1 to activate parkin. Nature. 2014; 510(7503):162-6 [Read the paper]


McLelland GL*, Soubannier V, Chen CX*, McBride HM, Fon EA. Parkin and PINK1 Function in a Vesicular Trafficking Pathway Regulating Mitochondrial Quality Control. EMBO J. 2014; 33(4):282-95. [Read the paper]


Bertolin G, Ferrando-Miguel R, Jacoupy M, Traver S, Grenier K*, Greene AW*, Dauphin A, Waharte F, Bayot A, Salamero J, Lombès A, Bulteau AL, Fon EA, Brice A, Corti O. The TOMM machinery is a molecular switch in PINK1 and PARK2/PARKIN-dependent mitochondrial clearance. Autophagy. 2013; 9(11):1801-17 [Read the paper]


Grenier K*, McLelland GL*, Fon EA. Parkin- and PINK1-Dependent Mitophagy in Neurons: Will the Real Pathway Please Stand Up? Front Neurol. 2013; 4:100 [Read the paper]


Trempe J-F*, Sauvé, V*, Grenier K, Seirafi, M, Tang MY, Ménade M, Krett J, Wong K, Kozlov G, Nagar B, Fon EA§, Gehring K§. Structure of parkin reveals mechanism of ubiquitin ligase activation. Science. 2013; 340: 1451-55 Epub 2013 May 9. §co-corresponding authors. [Read the paper]


Durcan TM*, Fon EA. Ataxin-3 and its E3 partners: Implications for Machado-Joseph disease.  Front. Neur. 2013 4:46. [Read the paper]


Trempe JF*, Fon EA. Structure and function of parkin, PINK1 and DJ-1, the three musketeers of neuroprotection.Front. Neur. 2013. 4:38. [Read the paper]


Ruan W*, Unsain N, Desbarats J, Fon EA§, Barker PA§. Wengen, the Sole Tumour Necrosis Factor Receptor in Drosophila, Collaborates with Moesin to Control Photoreceptor Axon Targeting During Development. PLoS One2013; 8(3): e60091. §co-corresponding author [Read the paper]


Daoud H, Noreau A, Rochefort D, Paquin-Lanthier G, Gauthier MT, Provencher P, Pourcher E, Dupré N, Chouinard S, Jodoin N, Soland V, Fon EA, Dion PA, Rouleau GA. Investigation of C9orf72 repeat expansions in Parkinson's disease. Neurobiol Aging. 2013 Jun; 34(6): 1710.e7-9. doi: 10.1016/j.neurobiolaging.2012.11.025 [Read the paper]


Grimes D, Gordon J, Snelgrove B, Lim-Carter I, Fon E, Martin W, Wieler M, Suchowersky O, Rajput A, Lafontaine AL, Stoessl J, Moro E, Schoffer K, Miyasaki J, Hobson D, Mahmoudi M, Fox S, Postuma R, Kumar H, Jog M; Canadian Neurological Sciences Federation. Canadian Guidelines on Parkinson's Disease. Can J Neurol Sci. 2012 Jul;39 (4 Suppl 4):S1-30 [Read the paper]


Klionsky DJ et al. Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. 2012 Apr;8(4):445-544 [Read the paper]


Greene AW*, Grenier K*, Aguileta MA, Muise S, Farazi R, Haque ME, McBride HM, Park DS, Fon EA. Mitochondrial Processing Peptidase Regulates PINK1 Processing, Import and Parkin Recruitment. EMBO Rep. 2012; 13(4):378-85 [Read the paper]


Soubannier V, McLelland GL, Zunino R, Braschi E, Rippstein P, Fon EA, McBride HM. A novel vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Curr. Biol. 2012; 22(2):135 [Read the paper]


Durcan TM, Kontogiannea M, Bedard N, Wing SS, Fon EA. Ataxin-3 deubiquitination is coupled to parkin ubiquitination via the E2 ubiquitin-conjugating enzyme. J. Biol. Chem. 2012; 287(1):531-41 [Read the paper]


Durcan TM, Fon EA. Mutant ataxin-3 promotes the autophagic degradation of parkin. Autophagy. 2011; 7(2):233-4 [Read the paper]


Durcan TM*, Kontogiannea M*, Thorarinsdottir T, Fallon L, Williams AJ, Djarmati A, Fantaneanu T, Paulson HL, Fon EA. The Machado-Joseph Disease-Associated Mutant form of Ataxin-3 Regulates Parkin Ubiquitination and Stability. Hum. Mol. Genet. 2011; 20(1):141-54 [Read the paper]


Irrcher I, Aleyasin H, Seifert EL, Hewitt SJ, Chhabra S, Phillips M, Lutz AK, Rousseaux MW, Bevilacqua L, Jahani-Asl A, Callaghan S, Maclaurin JG, Winklhofer KF, Rizzu P, Rippstein P, Kim RH, Chen CX, Fon EA, Slack RS, Harper ME, McBride HM, Mak TW, Park DS. Loss of the Parkinson's Disease-linked gene DJ-1 perturbs mitochondrial dynamics. Hum. Mol. Genet. 2010; 19(19):3734-46 [Read the paper]


Théard D, Labarrade F, Partisani M, Milanini J, Sakagami H, Fon EA, Wood SA, Franco M, Luton F. USP9x-mediated deubiquitination of EFA6 regulates de novo tight junction assembly. EMBO J. 2010;29(9):1499-509 [Read the paper]


Bouvier D, Tremblay ME, Riad M, Corera AT, Gingras D, Horn KE, Fotouhi M, Girard M, Murai KK, Kennedy TE, McPherson PS, Pasquale EB, Fon EA, Doucet G. EphA4 is localized in clathrin-coated and synaptic vesicles in adult mouse brain. J. Neurochem. 2010; 113:153-165 [Read the paper]


Trempe JF*, Chen CXQ*, Grenier K, Camacho EM, Kozlov G, McPherson PS, Gehring K, Fon EA. SH3 Domains from a Subset of BAR-Proteins Define a Novel Ubl-Binding Domain and Implicate Parkin in Synaptic Ubiquitination. Mol. Cell 2009; 36(6):1034-47. Co-corresponding authors [Read the paper]


Corera AT, Doucet G, Fon EA. Long-Term Potentiation in Isolated Dendritic Spines. PLoS ONE. 2009; 4(6): e6021. doi:10.1371/journal.pone.0006021. [Read the paper]


Cookson MR, Dauer W, Dawson TM, Fon EA, Guo M, Shen J. The roles of kinases in familial Parkinson’s disease. J. Neurosci. 2007; 27(44):11865-8 [Read the paper]


Kaiser P, Fon EA. Keystone Meeting on Ubiquitin and Signaling: Expanding Horizons at Big Sky. EMBO Rep. 2007; 8(9):817-22. [Read the paper]


Joch M*, Ase AR*, Chen CXQ*, MacDonald PA, Kontogiannea M, Corera AT, Brice A, Séguéla P, Fon EA. Parkin-Mediated Monoubiquitination of the PDZ Protein PICK1 Regulates ASIC Channel Activity. Mol. Biol. Cell. 2007; 18(8):3105-18[Read the paper]


Zhou L, Martinez SJ, Haber M, Jones EV, Bouvier D, Doucet G, Corera AT, Fon EA, Zisch AH, Murai KK. EphA4 signaling regulates phospholipase Cgamma1 activation, cofilin membrane association, and dendritic spine morphology. J. Neurosci. 2007; 27(19):5127-38.[Read the paper]


Fallon L, Bélanger CML, Corera AT, Kontogiannea M, Regan-Klapisz E, Moreau F, Voortman J, Haber M, Rouleau G, Thorarinsdottir T, Brice A, van Bergen en Henegouwen P, Fon EA. A Regulated Interaction with the UIM-protein Eps15 Implicates Parkin in EGF Receptor Trafficking and PI3K-Akt Signaling.Nat. Cell Biol. 2006; 8(8):834-42 [Read the paper]


Kalia SK, Lee S, Liu L, Crocker SJ, Thorarinsdottir TE, Smith PD, Glover JR, Fon EA, Park DS, Lozano AM. BAG5 inhibits parkin and enhances dopaminergic neuron degeneration. Neuron 2004; 44(6):931-45. [Read the paper]

 

Our lab is part of the Neuro (Montreal Neurological Institute and Hospital), a McGill research and teaching institute, delivering high quality patient care, as part of the Neuroscience Mission of the McGill University Health Centre.

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