PRINCIPAL INVESTIGATOR
Edward Fon, MD, FRCP (C)
ted.fon [at] mcgill.ca
Dr. Edward Fon, MD, FRCP(C) is a neurologist-scientist at the Montreal Neurological Institute-Hospital (The Neuro) specializing in movement disorders and a Professor in the Department of Neurology and Neurosurgery at McGill University. He is the Director of the FRQS Quebec Parkinson Network and the Scientific Director of The Neuro. He was trained at the Université de Montréal, McGill University and the University of California, San Francisco (UCSF). His research focuses on the molecular and cellular events leading to Parkinson's disease (PD). His laboratory has made contributions to understanding the function and cell biology of PD genes and in understanding how defects in these genes lead to PD. In particular, his lab has focused on understanding the function of Parkin, PINK1, α-synuclein, GBA, LRRK2, TMEM175 and DJ1, and has established the infrastructure at The Neuro to study these genes and pathways in human patient-derived induced pluripotent stem cells (iPSCs), which are differentiated into neurons, glia and 3D brain organoids. The lab is currently using these iPSC systems to establish a pipeline to better understand the role of lesser-studied PD genes, identified in recent genome-wide association studies (GWAS), in PD pathogenesis. In addition, Dr. Fon helped establish the Tanenbaum Open Science Institute (TOSI) at The Neuro and oversees its platforms including the Clinical Biological Imaging and Genetic repository (C-BIGr) and iPSC/CRISPR Early Drug Discovery Unit (EDDU).
List of publications - NCBI bibliography
POSTDOCTORAL FELLOWS
Thomas Goiran, PhD
thomas.goiran [at] mail.mcgill.ca
My research focuses on the effect induced by toxic accumulation of protein aggregates essentially composed of the protein Alpha-Synuclein. These aggregates are tought to be involved in neuronal decay in the brains of patients with Parkinson's disease, leading to loss of cognition and death. We do not know the genetic actors contributing to this neuronal toxicity. In order to identify and validate new target genes for the development of new therapeutic treatments, I combine the increased growth and division ability of cultured cell lines and the physiological relevance of a dopaminergic neuron model generated from induced pluripotent stem cells from healthy individuals and Parkinson's patients. The goal of my project is to reduce or prevent this toxicity and excessive neuronal death characteristic of Parkinson's disease.
List of publications
Roberts R., Bayne AN., Goiran T., Lévesque D., Boisvert FM., Trempe JF., Fon EA., (2021). Proteomic Profiling of Mitochondrial-Derived Vesicles in Brain Reveals Enrichment of Respiratory Complex Sub-assemblies and Small TIM Chaperones. J Proteome Res ; 20(1):506-517.
Checler F, Goiran T, Alves da Costa C. (2018). Nuclear TP53: An unraveled function as transcriptional repressor of PINK1. Autophagy ; 14(6):1099-1101.
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. (2018). Mfn2 ubiquitination by PINK1/parkin gates the p97-dependent release of ER from mitochondria to drive mitophagy. Elife ; pii: e32866
Goiran T, Duplan E, Rouland L, El Manaa W, Lauritzen I, Dunys J, You H, Checler F, Alves da Costa C. (2018). Nuclear p53-mediated repression of autophagy involves PINK1 transcriptional down-regulation. Cell Death and Differentiation ; 25(5):873-884
Goiran T, Duplan E, Chami M, Bourgeois A, El Manaa W, Rouland L, Dunys J, Lauritzen I, You H, Stambolic V, Biféri MG, Barkats M, Pimplikar SW, Sergeant N, Colin M, Morais VA, Pardossi-Piquard R, Checler F, Alves da Costa C. (2018). β-Amyloid Precursor Protein Intracellular Domain Controls Mitochondrial Function by Modulating Phosphatase and Tensin Homolog-Induced Kinase 1 Transcription in Cells and in Alzheimer Mice Models. Biological Psychiatry ; 1;83(5):416-427
Checler F, Goiran T, Alves da Costa C. (2017). Presenilins at the crossroad of a functional interplay between PARK2/PARKIN and PINK1 to control mitophagy: Implication for neurodegenerative diseases. Autophagy ; 13(11):2004-2005
CLoubière C, Goiran T, Laurent K, Djabari Z, Tanti JF, Bost F. (2015). Metformin-induced energy deficiency leads to the inhibition of lipogenesis in prostate cancer cells. Oncotarget ; 20;6(17):15652-61
Viotti J, Duplan E, Caillava C, Condat J, Goiran T, Giordano C, Marie Y, Idbaih A, Delattre JY, Honnorat J, Checler F, Alves da Costa C. (2014). Glioma tumor grade correlates with parkin depletion in mutant p53- linked tumors and results from loss of function of p53 transcriptional activity. Oncogene ; 3;33(14):1764-75
Duplan E, Sevalle J, Viotti J, Goiran T, Bauer C, Renbaum P, Levy-Lahad E, Gautier CA, Corti O, Leroudier N, Checler F, da Costa CA. (2013). Parkin differently regulates presenilin-1 and presenilin-2 functions by direct control of their promoter transcription. Journal of Molecular Cell Biology ; Apr;5(2):132-42
Mohamed Eldeeb, PhD
mohamed.eldeeb [at] mcgill.ca
My research aims at deciphering some of the molecular and structural basis of mitochondrial-quality control pathways in mammalian cells. Specifically, I am interested in understanding the molecular dialogue between protein quality-control and mitochondrial import machinery. In addition, I am interested in delineating the molecular basis of protein degradation roles in cellular demise in the context of PD.
List of publications
Eldeeb MA, Fahlman RP, Mohamed Ragheb, Mansoore Esmili and Mohamed Salla. (2019) Monitoring protein degradation in Nerve cells. JNC. Under review.
Eldeeb MA, Fahlman RP, Mohamed Ragheb and Mansoore Esmaili. (2019) Does N-terminal acetylation lead to protein degradation? BioEssays. In revision.
Eldeeb MA, Fahlman RP, Mansoore Esmaili and Edward Fon. (2019) Formylation of Eukaryotic Cytoplasmic Proteins: Linking Stress to Degradation. Trends Biochem. Sci. doi.org/10.1016/j.tibs.2018.12.008.
Eldeeb MA, Fahlman RP, Mansoore Esmaili and Mohamed Ragheb. (2018) Regulating apoptosis by degradation: The N-end rule-mediated regulation of apoptotic proteolytic fragments. International Journal of Molecular Sciences. 19, 3414.
Eldeeb MA, Fahlman RP. (2018) Does Too Much MAGIC Lead to Mitophagy? Trends in biochemical Sciences. P485-487, 2018.
Eldeeb MA, Ragheb, M.A. (2018) Post-translational N-terminal arginylation of protein fragments: a pivotal portal to proteolysis. Curr. Protein Pept. Sci. 19, 1214-1223
Eldeeb MA, Luana Leitao, Richard Fahlman. (2017) Emerging branches of the N-end rule pathways are revealing the sequence complexities of N-termini dependent protein degradation. Biochem. Cell. Biol. 10.1139/bcb-2017-0274.
Hou J, Eldeeb MA, Wang X. (2017) Beyond deubiquitylation: USP30-mediated regulation of mitochondrial homeostasis. AIMS Molecular Science. 4:219-223.
Eldeeb MA. (2017) Aging: when the ubiquitin–proteasome machinery collapses. Adv. Exp. Med. Biol. 1038:133-148.
Kramer DA, Eldeeb MA, Wuest M, Mercer J, Fahlman RP. (2017) Proteomic characterization of EL4 lymphoma derived tumors upon chemotherapy treatment reveals potential roles for lysozomes and caspase6 during tumor cell death in vivo. Proteomics. 17, 12-17.
AlMatarM., Eldeeb MA, Makky, E.A. et al. (2017) Are there any other compounds isolated from Dermacoccus spp at all? Curr. Microbiol. 74:132-144.
Eldeeb MA, Fahlman RP. (2016) The N-end rule: The beginning determines the end.Protein and Peptide Letters. 23:343-348.
Eldeeb MA, Fahlman RP. (2016) Phosphorylation impacts then-end rule degradation of the proteolytically activated form of BMX kinase. J. Biol. Chem. 291:22757-22768.
Eldeeb MA, Fahlman RP. (2014) The anti-apoptotic form of tyrosine kinase Lyn that is generated by proteolysis is degraded by the N-end rule pathway. Oncotarget. 5:2714–22.
Yogitha Thattikota, PhD
yogitha.thattikota [at] mcgill.ca
List of publications
Thattikota Y., Tollis S., Palou R., Vinet J., Tyers M., D'Amours D. (2018) Cdc48/VCP Promotes Chromosome Morphogenesis by Releasing Condensin from Self-Entrapment in Chromatin. Mol. Cell. 69, 664-676 e665.
Chatterjee G., Sankaranarayanan S.R., Guin K., Thattikota Y., Padmanabhan S., Siddharthan R., Sanyal K. (2016) Repeat-Associated Fission Yeast-Like Regional Centromeres in the Ascomycetous Budding Yeast Candida tropicalis. PLoS Genet. 12, e1005839.
Kanshin E., Kubiniok P., Thattikota Y., D'Amours D., Thibault P.(2015) Phosphoproteome dynamics of Saccharomyces cerevisiae under heat shock and cold stress. Mol. Syst. Biol. 11, 813
Robellet X*., Thattikota Y*., Wang F., Wee T.L., Pascariu M., Shankar S., Bonneil E., Brown C.M., D'Amours D.(2015) A high-sensitivity phospho-switch triggered by Cdk1 governs chromosome morphogenesis during cell division. Genes Dev. 29, 426-439. *equal contribution
Clarisse Orniacki, PhD
clarisse.orniacki [at] mail.mcgill.ca
Variants of the GBA1 gene encoding the lysosomal enzyme glucocerebrosidase are one of the most common risk factors for Parkinson’s Disease (PD). In addition, mutations in other lysosomal proteins have recently been linked to increased risk and earlier age at onset in GBA1-associated PD, suggesting an important role for lysosomal proteins in developing the disease. My projects in the lab use cellular models including dopaminergic neurons and microglia derived from human iPSC to characterize the roles of these lysosomal protein in the context of PD, and to understand the molecular mechanisms behind greater susceptibility to disease conferred by patient’s mutations. Shedding light on these mechanisms is key to finding relevant targets and improving the treatment of PD.
List of publications
Orniacki, C., Verrico, A., Souquet, B., Pelletier, S., Jourdren, L., Coulpier, F., Benetti, S., Doye V. (2022). Y-complex nucleoporins independently contribute to nuclear pore assembly and gene regulation in neuronal progenitors. J. Cell Sci. 136, jcs261151.
Gonzalez-estevez, A.*, Verrico, A.*, Orniacki, C., Reina-San-Martin B., Doye V. (2021). Integrity of the short arm of nuclear pore Y-complex is required for mouse embryonic stem cell growth and differentiation. J. Cell Sci. 134. jcs258340.
Langouët, M., Gorka, D., Orniacki, C., Dupont-Thibert, C.M., Chung, M.S., Glatt-Deeley, H.R., Germain, N., Crandall, L.J., Cotney, J.L., Stoddard, C.E., Lalande M., Chamberlain S.J. (2020) Specific ZNF274 binding interference at SNORD116 activates the maternal transcripts in Prader-Willi syndrome neurons. Human Mol. Genetics 29. 3285-3295.
PhD STUDENTS
Emma MacDougall
emma.macdougall [at] mail.mcgill.ca
I study the role of LRRK2 and Rab GTPases in the pathogenesis of Parkinson's disease by using induced pluripotent stem cell (iPSC) based models. I focus particularly on understanding the role of LRRK2-Rab signaling in iPSC derived microglia, and co-culturing microglia and neurons in 3 dimensions. My goal is to unravel the mechanisms underlying LRRK2-Rab communication and neuroinflammation in Parkinson's disease.
List of publications
Yi, W., MacDougall, E. J., Tang, M. Y., Krahn, A. I., Gan-Or, Z., Trempe, J. Fon, E. A. (2019) The landscape of Parkin variants reveals pathogenic mechanisms and therapeutic targets in Parkinson’s disease. Hum. Mol. Genet. 28, 2811–2825
Fava, V. M., Xu, Y. Z., Lettre, G., Van Thuc, N., Orlova, M., Thai, V. H., Tao, S., Croteau, N., Eldeeb, M. A., MacDougall, E. J., Cambri, G., Lahiri, R., Adams, L., Fon, E. A., Trempe, J., Cobat, A., Alcaïs, A., Abel, L., Schurr, E. (2019) Pleiotropic effects for Parkin and LRRK2 in leprosy type-1 reactions and Parkinson’s disease. Proc. Natl. Acad. Sci. U.S.A. 116, 15616–15624
Eldeeb, M. A., MacDougall, E. J., Ragheb, M. A., Fon, E. A. (2019) Beyond ER: Regulating TOM-Complex-Mediated Import by Ubx2. Trends Cell Biol. 29, 687–689
Ghislaine Deyab
ghislaine.deyab [at] mail.mcgill.ca
My research focuses on characterizing neural activity present in human derived midbrain organoids as a model of Parkinson’s disease (PD). Organoids are a promising tool that can be used to study neurodegenerative diseases on a patient specific level. There is evidence showing that organoids exhibit certain aspects of disease pathology such as the inclusion of protein aggregates and neuronal death, complementary to what we see occur in human models of PD. However, there is extensive literature showing that PD also causes abnormal activity in basal ganglia circuits, namely increased bursting activity and synchronization between basal ganglia nuclei. My aim is to determine whether midbrain organoids can accurately model the changes in neural activity associated with PD. To do this, I will conduct an in-depth analysis of electrophysiological properties, pathological markers, and pharmacological testing on PD patient-derived hMOs and their isogenic controls. My goal is to validate the reliability of using organoids as a model to study neurodegenerative diseases in a patient specific manner.
List of publications
Khoo S.Y.-S., Lecocq M.,Deyab, G., Chaudhri, N. (2019) Context and topography determine the role of basolateral amygdala metabotropic glutamate receptor 5 in appetitive Pavlovian responding. Neuropsychopharmacology 44(9):1524-1533
Zaid Al-Azzawi
zaid.al-azzawi [at] mail.mcgill.ca
My project is focused on the biochemical profiling of α-synuclein aggregates from various cellular models of Parkinson’s disease (PD). α-synuclein aggregation is a pathological hallmark of a group of diseases known as synucleinopathies. Recent research has shown α-synuclein forms different fibrils capable of adopting self-perpetuating conformations, known as strains, which may characterize distinct clinical synucleinopathy syndromes. This could explain why and how α-synuclein aggregates can be present in various Parkinsonian diseases and yet lead to different patterns of disease progression and cellular damage. Leveraging the advantages of patient-derived 3D midbrain organoids, my goal is to develop a bioassay for the detection and characterization of pathological α-synuclein aggregates and to screen for patient-specific therapeutics.
List of publications
Arshad H, Patel Z, Mehrabian M, Bourkas MEC, Al-Azzawi ZAM, Schmitt-Ulms G, Watts JC. (2021) The aminoglycoside G418 hinders de novo prion infection in cultured cells. J Biol Chem. 297(3):101073
So RWL, Chung SW, Lau HHC, Watts JJ, Gaudette E, Al-Azzawi ZAM, Bishay J, Lin LT, Joung J, Wang X, Schmitt-Ulms G. (2019) Application of CRISPR genetic screens to investigate neurological diseases. Mol Neurodegener. 14(1):41.
Bourkas MEC, Arshad H, Al-Azzawi ZAM, Halgas O, Shikiya RA, Mehrabian M, Schmitt-Ulms G, Bartz JC, Watts JC. (2019) Engineering a murine cell line for the stable propagation of hamster prions. J Biol Chem. 294(13):4911-4923.
Nathan Karpilovsky
nathan.karpilovsky [at] mail.mcgill.ca
My research at the Fon lab focuses on the effect of novel genes on α-synuclein aggregate propagation in Parkinson’s Disease. The spread of α-synuclein throughout the central nervous system is believed to be one of the main contributors to the progressive nature of the disease. Particularly, I am interested in the mechanisms involved in the uptake and accumulation of α-synuclein aggregates in neurons. In my research, I utilize CRISPR activation and interference to study the effect of specific gene modulation on the accumulation of lab-generated α-synuclein preformed fibrils in cells. My goal is to elucidate the mechanisms of α-synuclein uptake and accumulation in iPSC-derived neurons, and uncover possible therapeutic targets for the treatment of Parkinson’s disease.
List of publications
MSc STUDENTS
Isabella Pietrantonio
isabella.pietrantonio [at] mail.mcgill.ca
The accumulation of protein aggregates composed mainly of alpha-synuclein is a major hallmark of Parkinson’s disease. The mechanisms through which these aggregates exert their toxicity have not yet been fully elucidated, yet their ability to disrupt degradation systems within the cell has been suggested. The lysosome is at the heart of these degradation pathways, therefore highlighting its importance. My project aims to explore the role of lysosomal function in Parkinson's Disease (PD) pathology by investigating genetic modulators of lysosomal rupture induced by pre-formed fibrils of recombinant alpha-synuclein (PFFs).
List of publications
Donovan Worral
donovan.worrall [at] mail.mcgill.ca
I work on the characterization of antibodies that target GWAS-associated Parkinson's disease genes. I will then use these antibodies to investigate these understudied genes with the hope of discovering their role in PD pathology.
List of publications
Worrall D, Ayoubi R, Fotouhi M, Southern K, McPherson PS, Laflamme C, NeuroSGC/YCharOS/EDDU collaborative group, ABIF Consortium. (2023) The identification of high-performing antibodies for TDP-43 for use in Western Blot, immunoprecipitation and immunofluorescence. F1000Research 12, 277
Ayoubi R, Ryan J, Biddle MS, Alshafie W, Fotouhi M, Bolivar SG, Ruiz Moleon V, Eckmann P, Worrall D, McDowell I, Southern K, Reintsch W, Durcan TM, Brown C, Bandrowski A, Virk H, Edwards AM, McPherson P, Laflamme C (2023) Scaling of an antibody validation procedure enables quantification of antibody performance in major research applications. eLife 12, RP91645
Ayoubi R, Worrall D, et al. (2023) Antibody Characterization Report for Angiogenin. Zenodo
Fotouhi M, Ryan J, Reintsch W, Worrall D, et al. (2023) Antibody Characterization Report for Alsin. Zenodo
Fotouhi M, Ryan J, Worrall D, et al. (2023) Antibody Characterization Report for RNA-binding protein TIA1. Zenodo
Worrall D, et al. (2022) Antibody Characterization Report for Rho Gdp-dissociation Inhibitor 1 (rho GDI 1). Zenodo
RESEARCH ASSOCIATES
Rhalena Thomas, PhD
rhalena.thomas [at] mcgill.ca
I develop analysis tools for induced pluripotent stem cells derived neurons and 3D tissue models ("mini-brains"). My goal is to integrate transcriptional data from single cell sequencing and cellular imaging data to understand the pathological processes involved in Parkinson's disease.
List of publications
Del Cid-Pellitero E, Tavassoly O, Larroquette F, Cai E, Thomas RA, Soubannier V, Luo W, Durcan TM, Fon EA. (2021) 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.
Vogel JW, La Joie R, Grothe MJ, Diaz-Papkovich A, Doyle A, Vachon-Presseau E, Lepage C, de Wael RV, Thomas RA, Iturria-Medina Y, Bernhardt B. (2020) A molecular gradient along the longitudinal axis of the human hippocampus informs large-scale behavioral systems. Nature communications 11(1):1-7
Thomas RA, Gibon J, De Leon, A, Chen, CXQ, Chierzi, S, Baulac, S, Murai, KK, Barker PA. (2018) The Nogo Receptor Ligand LGI1 Regulates Synapse Number and Synaptic Activity in Hippocampal and Cortical Neurons. eNeuro 0185-18
Thomas RA, Metzen MG and Chacron MJ. (2018) Weakly electric fish distinguish between envelope stimuli arising from different behavioral contexts. Journal of experimental biology 221: jeb178244
Gibon J, Unsain N, Gamache K, Thomas RA, De Leon A, Johnstone A, Nader K, Sequela P, Barker PA. (2016) The X-linked inhibitor of apoptosis regulates long-term depression and learning rate. FASEB J. 30(9):3083
Thomas RA, Ambalavana A, Rouleau GA, Barker PA. (2016) Identification of genetic variants of LGI1 and RTN4R (NgR1) linked to schizophrenia that are defective in NgR1–LGI1 signaling. Molecular Genetics and Genomic Medicine. 4(4): 447–456
Kommaddi R, Thomas R, Ceni C, Daigneault K, Barker PA. (2011) Trk-dependent ADAM17 activation facilitates neurotrophin survival signalling. FASEB J. 10-173740
Ceni C, Kommaddi R, Thomas R, Vereker E, McPherson PM, Ritter B, Liu X, Barker PA. (2010) The p75NTR intracellular domain is generated by neurotrophin-induced receptor cleavage to potentiate Trk signalling. Journal of Cell Science 123(13):2299-307
Thomas R, Favell K, Morante-Redolat JM, Pool, M, Kent C, Wright M, Daignault K, Ferraro G, Montcalm S, Durocher Y, Fournier A, Perez-Tur J, Barker PA. (2010) LGI1 is a Novel Nogo Receptor 1 ligand that antagonizes myelin-based growth inhibition. Journal of Neuroscience 30(19):6607-12
Cornelia Zorca, PhD
cornelia.zorca [at] mcgill.ca
CRISPR/Cas9 screening of PD-associated genes
List of publications
Lessard, F., Ingelmann, S., Trahan, C., Huot, G., Saint-Germain, E., Mignacca, L., DelToro, N., Lopes-Paciencia, S., Le Calve, B., Montero, M., Deschenes-Simard, X., Bury, M., Moiseeva, O., Rowell, M-C., Zorca, C.E., Zenklusen, D., Brakier-Gingras, L., Boudreau, V., Oeffinger, M., Ferbeyre, G. Ribosome biogenesis defects in senescence reveal a novel checkpoint pathway to control CDK4: in press Nat. Cell Biol.
Zorca.C.E.*, Rahman, S.*, Noutahi, E., Krause, M.R., Zenklusen, D. Single-cell profiling reveals that eRNAs accumulation at enhancer-promoter loops is not required for bursting transcription: Nucleic Acid Res., 45(6): 3017-3030, 2017.
*equal contribution
Zorca, C.E., Kim, L.K., Kim, Y.J., Krause,M.R., Zenklusen, D., Spilianakis, C.G., Flavell, R.A. Myosin VI regulates gene pairing and transcriptional pause release in T cells: PNAS, 112(13) E1587-E1593, 2015.
Kim, L.K., Esplugues, E., Zorca, C.E., Parisi, F., Kluger, Y., Kim, T.H., Galjart, N.J., Flavell, R.A., Oct-1 regulates IL-17 expression by directing interchromosomal associations in conjunction with CTCF in T cells: Mol. Cell., 54(1): 56-66, 2014.
Zorca, S.M., Zorca, C.E., The Legacy of a Founding Father of Modern Cell Biology: George Emil Palade (1910-2008): YJBM., 84(2): 113-116, 2011.
Granneman, S., Lin, C.Y., Champion, E.A., Nandineni, M.R., Zorca, C., Baserga, S.J., The nucleolar protein Esf2 interacts directly with the DexD/H box RNA helicase, Dbp8, to stimulate ATP hydrolysis: Nucleic Acid Res., 34(10): 3189-3199, 2006.
Vincent Soubannier, PhD
vincent.soubannier [at] mcgill.ca
I work as a microscopy specialist in Dr. Fon’s lab. I perform basic training for users on routine and advanced microscopy on a widefield live imaging system. I work with researchers to determine appropriate equipment for experiments and to develop experimental designs to address specific research questions. This includes consultation on image processing and analysis and the development of automatized analytic tools through imageJ macros, for instance. I finally do regular maintenance of the microscopy equipment and initiate repairs if necessary.
List of publications
Tavassoly O, Del Cid-Pellitero E, Larroquette F, Cai E, Thomas RA,Soubannier V, Luo W, Durcan TM, Fon EA. (2021) 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.
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. (2020) Stimulation of L-type calcium channels increases tyrosine hydroxylase and dopamine in ventral midbrain cells induced from somatic cells. Stem Cells Transl Med.
Methot L, Soubannier V, Hermann R, Campos E, Li S, Stifani S. (2018) Nuclear factor-kappaB regulates multiple steps of gliogenesis in the developing murine cerebral cortex. Glia
Thomas RA, Gibon J, Chen CXQ, Chierzi S, Soubannier V, Baulac S, Séguéla P, Murai K, Barker PA. (2018) The Nogo Receptor Ligand LGI1 Regulates Synapse Number and Synaptic activity in Hippocampal and Cortical Neurons. eNeuro
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. (2018) Disruption of GRIN2B Impairs Differentiation in Human Neurons. Stem Cell Reports.
Soubannier V, Stifani S. (2017) NF-κB Signalling in Glioblastoma. Biomedicines.
Gaub P, de Léon A, Gibon J, Soubannier V, Dorval G, Séguéla P, Barker PA. (2016) HBpF-proBDNF: A New Tool for the Analysis of Pro-Brain Derived Neurotrophic Factor Receptor Signaling and Cell Biology. PloS One.
Patten DA, Wong J, Khacho M, Soubannier V, Mailloux RJ, Pilon-Larose K, MacLaurin JG, Park DS, McBride HM, Trinkle-Mulcahy L, Harper ME, Germain M, Slack RS. (2014) OPA1-dependent cristae modulation is essential for cellular adaptation to metabolic demand. EMBO J.
McLelland GL, Soubannier V, Chen CX, McBride HM, Fon EA. (2014) Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J.
Soubannier V, Rippstein P, Kaufman BA, Shoubridge EA, McBride HM. (2012) Reconstitution of mitochondria derived vesicle formation demonstrates selective enrichment of oxidized cargo. PloS One.
Soubannier V,McLelland GL, Zunino R, Braschi E, Rippstein P, Fon EA, McBride HM. (2012) A vesicular transport pathway shuttles cargo from mitochondria to lysosomes. Curr. Biol.
McBride H, Soubannier V (2010) Mitochondrial function: OMA1 and OPA1, the grandmasters of mitochondrial health. Curr. Biol.
Rabl R, Soubannier V, Scholz R, Vogel F, Mendl N, Vasiljev-Neumeyer A, Körner C, Jagasia R, Keil T, Baumeister W, Cyrklaff M, Neupert W, Reichert AS. (2009) Formation of cristae and crista junctions in mitochondria depends on antagonism between Fcj1 and Su e/g. J. Cell. Biol.
Soubannier V, McBride HM. (2009) Positioning mitochondrial plasticity within cellular signaling cascades. Biochim. Biophys. Acta.
Giraud MF, Paumard P, Soubannier V, Vaillier J, Arselin G, Salin B, Schaeffer J, Brèthes D, di Rago JP, Velours J. (2002) Is there a relationship between the supramolecular organization of the mitochondrial ATP synthase and the formation of cristae? Biochim. Biophys. Acta.
Paumard P, Vaillier J, Coulary B, Schaeffer J, Soubannier V, Mueller DM, Brèthes D, di Rago JP, Velours J. (2002) The ATP synthase is involved in generating mitochondrial cristae morphology. EMBO J.
Soubannier V, Vaillier J, Paumard P, Coulary B, Schaeffer J, Velours J. (2002) In the absence of the first membrane-spanning segment of subunit 4(b), the yeast ATP synthase is functional but does not dimerize or oligomerize. J. Biol. Chem.
Velours J, Vaillier J, Paumard P, Soubannier V, Lai-Zhang J, Mueller DM. (2001) Bovine coupling factor 6, with just 14.5% shared identity, replaces subunit h in the yeast ATP synthase. J. Biol. Chem.
Velours J, Paumard P, Soubannier V, Spannagel C, Vaillier J, Arselin G, Graves PV. (2000) Organisation of the yeast ATP synthase F(0):a study based on cysteine mutants, thiol modification and cross-linking reagents. Biochim. Biophys. Acta.
Soubannier V, Rusconi F, Vaillier J, Arselin G, Chaignepain S, Graves PV, Schmitter JM, Zhang JL, Mueller D, Velours J. (1999) The second stalk of the yeast ATP synthase complex: identification of subunits showing cross-links with known positions of subunit 4 (subunit b). Biochemistry
Roxanne Larivière, PhD
roxanne.lariviere [at] mcgill.ca
My research interest lies in better understanding the role of GWAS-associated PD genes and characterize the lesser-studied PD genes in genetically-modified induced pluripotent stem cell derived midbrain organoids. With the use of PD phenotypic assays and unbiased multi-omics, we hope to disentangle the PD GWAS-ome by uncovering new pathways or mechanisms in PD pathology and new key targets for therapy
List of publications
Choquet K, Pinard M, Yang S, Moir RD, Poitras C, Dicaire M-J, Sgarioto N, Larivière R, Kleinman CL, Willis IM, Gauthier M-S, Coulombe B, Brais B. (2019) The leukodystrophy mutation Polr3b R103H causes homozygote mouse embryonic lethality and impairs RNA Polymerase III biogenesis. Mol. Brain
Larivière R, Sgarioto N, Toscano Márquez B, Gaudet R, Choquet K, McKinney RA, Watt AJ, Brais B. (2019) Sacs R272C missense homozygous mice develop an ataxia phenotype. Mol. Brain
Walker CL, Uchida A, Li Y, Trivedi N, Fenn JD, Monsma PC, Larivière RC, Julien JP, Jung P, Brown A. (2019) Local Acceleration of Neurofilament Transport at Nodes of Ranvier. J Neurosci.
Gentil BJ, Lai GT, Menade M, Larivière R, Minotti S, Gehring K, Chapple JP, Brais B, Durham HD. (2018) Sacsin, mutated in the ataxia ARSACS, regulates intermediate filament assembly and dynamics. FASEB J.
Ady V, Toscano-Márquez B, Nath M, Chang PK, Hui J, Cook A, Charron F, Larivière R, Brais B, McKinney RA, Watt AJ. (2018) Altered synaptic and firing properties of cerebellar Purkinje cells in a mouse model of ARSACS. J Physiol.
Duncan EJ, Larivière R , Bradshaw TY, Longo F, Sgarioto N, Hayes MJ, Romano LEL, Nethisinghe S, Giunti P, Bruntraeger MB, Durham HD, Brais B, Maltecca F, Gentil BJ, Chapple JP. (2017) Altered organization of the intermediate filament cytoskele-ton and relocalization of proteostasis modulators in cells lacking the ataxia protein sacsin. Hum Mol Genet.
Choquet K, Yang S, Moir RD, Forget D, Larivière R , Bouchard A, Poitras C, Sgarioto N, Dicaire MJ, Noohi F, Kennedy TE, Roch-ford J, Bernard G, Teichmann M, Coulombe B, Willis IM, Klein-man CL, Brais B. (2017) Absence of neurological abnormalities in mice homozygous for the Polr3a G672E hypomyelinating leukodystrophy mutation. Mol Brain.
Larroquette F, Seto L, Gaub PL, Kamal B, Wallis D, Larivière R, Vallée J, Robitaille R, Tsuda H. (2015) Vapb/Amyotrophic lateral sclerosis 8 knock-in mice display slowly progressive motor behavior defects accompanying ER stress and autophagic response. Hum Mol Genet.
Larivière R, Gaudet R, Gentil BJ, Girard M, Conte TC, Minotti S, Leclerc-Desaulniers K, Gehring K, McKinney RA, Shoubridge EA, McPherson PS, Durham HD, Brais B. (2015) Sacs knockout mice present pathophysiological defects underlying autosomal recessive spastic ataxia of Charlevoix-Saguenay. Hum Mol Genet.
Thiffault I, Dicaire MJ, Tetreault M, Huang KN, Demers-La-marche J, Bernard G, Duquette A, Larivière R, Gehring K, Montpetit A, McPherson PS, Richter A, Montermini L, Mercier J, Mitchell GA, Dupré N, Prévost C, Bouchard JP, Mathieu J, Brais B. (2013) Diversity of ARSACS mutations in French-Canadians. Can J Neurol Sci.
Girard M1, Larivière R1, Parfitt DA, Deane EC, Gaudet R, Noss-ova N, Blondeau F, Prenosil G, Vermeulen EGM, Duchen MR, Richter A, Shoubridge EA, Gehring K, McKinney RA, Brais B, Chapple JP, and McPherson PS. (2012 10) Mitochondrial dysfunction and Purkinje cell loss in autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) PNAS (1: co-authors)
Ezzi SA, Larivière R, Urushitani M, Julien JP. (2010) Neuronal over-ex-pression of chromogranin A accelerates disease onset in a mouse model of ALS. J. Neurochem.
Dequen F, Filali M, Larivière RC, Perrot R, Hisanaga S, Julien JP. (2010) Reversal of neuropathy phenotypes in conditional mouse model of Charcot-Marie-Tooth disease type 2E. Hum Mol Genet.
Gros-Louis F, Soucy G, Larivière R, Julien JP. (2010) Intracerebroven-tricular infusion of monoclonal antibody or its derived Fab fragment against misfolded forms of SOD1 mutant delays mortality in a mouse model of ALS. J Neurochem.
Eriksson KS, Zhang S, Lin L, Larivière RC, Julien JP, Mignot E. (2008) The type III neurofilament peripherin is expressed in the tubero-mammillary neurons of the mouse. BMC Neurosci.
Millecamps S, Robertson J, Lariviere R, Mallet J, Julien JP. (2006) Defective axonal transport of neurofilament proteins in neurons overexpressing peripherin. J Neurochem.
Gros-Louis F, Larivière R, Gowing G, Laurent S, Camu W, Bouchard JP, Meininger V, Rouleau GA, Julien JP. (2004) A frameshift deletion in peripherin gene associated with amyotrophic lateral sclerosis. J Biol Chem.
Nguyen MD, Shu T, Sanada K, Larivière RC, Tseng HC, Park SK, Julien JP, Tsai LH. (2004) A NUDEL¬dependent mechanism of neurofil-ament assembly regulates the integrity of CNS neurons. Nat Cell Biol.
Lariviere RC, Julien JP. (2004) Functions of intermediate filaments in neuronal development and disease. J Neurobiol. Review.
Larivière RC, Beaulieu JM, Nguyen MD, Julien JP. (2003) Peripherin is not a contributing factor to motor neuron disease in a mouse model of amyotrophic lateral sclerosis caused by mutant superoxide dismutase. Neurobiol Dis.
Larivière RC, Nguyen MD, Ribeiro-da-Silva A, Julien JP. (2002) Reduced number of unmyelinated sensory axons in peripher-in null mice. J Neurochem.
Nguyen MD, Larivière RC, Julien JP. (2001) Deregulation of Cdk5 in a mouse model of ALS: toxicity alleviated by perikaryal neurofil-ament inclusions. Neuron.
Nguyen MD, Larivière RC, Julien JP. (2000) Reduction of axonal caliber does not alleviate motor neuron disease caused by mutant superoxide dismutase 1. Proc Natl Acad Sci U S A.
Esther Del Cid Pellitero, PhD
esther.delcidpellitero [at] mcgill.ca
In Dr. Fon lab, I am the manager of pre-clinical and research mouse projects. I study the implications α–synuclein propagation as well as Parkin, Pink 1 and related proteins in Parkinson Disease.
List of publications
Tullo S, Miranda AS, Del Cid-Pellitero E, Lim MP, Gallino D, Attaran A, Patel R, Novikov V, Park M, Beraldo FH, Luo W, Shlaifer I, Durcan TM, Bussey TJ, Saksida LM, Fon EA, Prado VF,. Prado MAM,M. Chakravarty M.(2022) Presymptomatic neuroanatomical and cognitive biomarkers of alphasynuclein propagation in a mouse model of synucleinopathy.nbsp;Preprint
Lackie RE, de Miranda AS, Lim MP, Novikov V, Madrer N, Karunatilleke NC, Rutledge BS, Tullo S, Brickenden A, Maitland MER, Greenberg D, Gallino D, Luo W, Attaran A, Shlaifer I, Del Cid-Pellitero E, Schild-Poulter C, Durcan TM, Fon EA, Duennwald M, Beraldo FH, Chakravarty MM, Bussey TJ, Saksida LM, Soreq H, Choy WY, Prado VF, Prado MAM.(2022) Stress-inducible phosphoprotein 1 (HOP/STI1/STIP1) regulates the accumulation and toxicity of α-synuclein in vivo.nbsp;Acta Neuropathol. 144(5):881-910
Bayati A, Banks E, Han C, Luo W, Reintsch WE, Zorca CE, Shlaifer I, Del Cid-Pellitero E, Vanderperre B, McBride HM, Fon EA, Durcan TM, McPherson PT.(2022) Rapid macropinocytic transfer of a-synuclein to lysosomes.nbsp;Cell Reports. 40, 111102
Bérard AM, Sheta R , Malvaut S, Rodriguez-Aller R, Teixeira M, Idi W, Turmel R, Alpaugh M, Dubois M, Dahmene M, Salesse C, Lamontagne-Proulx J, St-Pierre JM, Tavassoly O, Luo W, Del Cid-Pellitero E, Qazi R, Jeong JW, Durcan TM, Vallières L, Tremblay ME, Soulet D, Lévesque M, Cicchetti F, Fon EA, Saghatelyan A, Oueslati A. (2022) A light-inducible protein clustering system for in vivo analysis of α-synuclein aggregation in Parkinson disease.nbsp;PLoS Biol. 20(3): e3001578
Kwan C, Kang MS, Nuara SG, Gourdon JC, Bédard D, Tardif CL, Hopewell R, Ross K, Bdair H, Hamadjida A, Massarweh G, Soucy JP, Luo W, Del Cid-Pellitero E, Shlaifer I, Durcan TM, Fon EA, Rosa-Neto P, Frey S, Huot P.(2021) Co-registration of imaging modalities (MRI, CT and PET) to perform frameless stereotaxic robotic injections in the common marmoset. Neuroscience. S0306-4522(21)00560-1
Tavassoly O*, Del Cid-Pellitero E*, Larroquette F, Cai E, Thomas RA, Soubannier V, Luo W, Durcan TM, Fon EA. (2021) 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. *co-first authors
Jin JW*, Fan X*, Del Cid-Pellitero E*, 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. (2021) Development of an α-synuclein knockdown peptide and evaluation of its efficacy in Parkinson’s disease models. Communications Biology. 4, 232 *co-first authors
Manecka DL, Luo W, Krahn A, Del Cid-Pellitero E, Shlaifer I, Beitel LK, Rao T, Durcan TM. (2020) Production of Recombinant α-Synuclein Monomers and Preformed Fibrils (PFFs). DOI:10.5281/zenodo.3372888.
Del Cid-Pellitero E, Shlaifer R, Wen L, Krahn A, Nguyen-Renou E, Manecka DL, Trisha R, Beitel L, Durcan TM.(2020) Characterization of αSynuclein Preformed Fibrils (PFFs). DOI:10.5281/zenodo.3385345
Martínez GF, Fan X*, Gazal NG, Quassollo G, Szalai AM, Del Cid-Pellitero E, Durcan TM, Fon EA, Bisbal M, Stefani FD and Unsain N. (2020) Quantitative expansion microscopy for the characterization of the spectrin periodic skeleton of axons using fluorescence microscopy. Scientific Report. 10:2917
Toossi H, Del Cid-Pellitero E, Jones BE. (2018) Homeostatic Changes in GABA and Acetylcholine Muscarinic Receptors on GABAergic Neurons in the Mesencephalic Reticular Formation following Sleep Deprivation. eNeuro. 3;4(6)
Reynolds LM, Pokinko M, Torres-Berrío A, Cuesta S, Lambert LC, Del Cid-Pellitero E, Wodzinski M, Manitt C, Krimpenfort P, Kolb B, Flores C. (2018) DCC Receptors Drive Prefrontal Cortex Maturation by Determining Dopamine Axon Targeting in Adolescence. Biol Psychiatry. 15:181-192
Del Cid-Pellitero E, Plavski A, Mainville L, Jones BE. (2017) Homeostatic Changes in GABA and Glutamate Receptors on Excitatory Cortical Neurons during Sleep Deprivation and Recovery. Front Syst Neurosci. 31;11-17
Toossi H, Del Cid-Pellitero E, Jones BE. (2017) Homeostatic regulation through GABA and acetylcholine muscarinic receptors of motor trigeminal neurons following sleep deprivation. Brain Struct Funct. 222:3163-3178
Toossi H, Del Cid-Pellitero E, Jones BE. (2016) GABA Receptors on Orexin and Melanin-Concentrating Hormone Neurons Are Differentially Homeostatically Regulated Following Sleep Deprivation. eNeuro. 9;3(3)
Del Cid-Pellitero E, Garzón M. (2014) Hypocretin1/orexinA-immunoreactive axons form few synaptic contacts on rat ventral tegmental area neurons that project to the medial prefrontal cortex. BMC Neurosci. 15:10
Del Cid-Pellitero E, Jones BE. (2012) Immunohistochemical evidence for synaptic release of GABA from melanin- concentrating hormone containing varicosities in the locus coeruleus. Neuroscience. 223:269-276
Toossi H, Del Cid-Pellitero E, Stroh T, Jones BE. (2012) Somatostatin varicosities contain the vesicular GABA transporter and contact orexin neurons in the hypothalamus. Eur J Neurosci. 10: 3388-3395
Del Cid-Pellitero E, Garzón M. (2011) Hypocretin 1/orexin A axon targeting of laterodorsal tegmental nucleus neurons projecting to the rat medial prefrontal cortex. Cerebral Cortex. 21:2762-2773
Del Cid-Pellitero E, Garzón M. (2011) Medial prefrontal cortex receives input from dorsal raphe nucleus neurons targeted by hypocretin1/orexinA-containing axons. Neuroscience. 172:30-43
Del Cid-Pellitero E, Garzón M. (2011) Hypocretin 1/orexin A-containing axons innervate locus coeruleus neurons that project to the rat medial prefrontal cortex. Implication in the sleep-wakefulness cycle and cortical activation. Synapse. 65:843-857
Del Cid-Pellitero E, Garzón M. (2007) Modulation by the hypocretinergic/orexinergic neurotransmission system in sleep-wakefulness cycle states. Rev. Neurol. 45:482-49
MANAGEMENT
Frédérique Larroquette, MSc
frederique.larroquette [at] mcgill.ca
I am managing the lab in its day to day organization. I'm also directing operations for our latest initiative, the Neuro-CERVO Alliance for Drug Discovery in brain diseases.
List of publications
Tavassoly O, Del Cid-Pellitero E, Larroquette F, Cai E, Thomas RA, Soubannier V, Luo W, Durcan TM, Fon EA. (2021) 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.
Mohamed NV., Larroquette F., Beitel LK, Fon EA, Durcan TM. (2019) One step into the future: new iPSC tools to advance research in Parkinson’s disease and neurological disorders. Journal of Parkinson’s disease doi: 10.3233/JPD-181515
Larroquette F, Seto L, Gaub PL, Kamal B, Wallis D, Larivière R, Vallée J, Robitaille R, Tsuda H. (2015) Vapb/Amyotrophic lateral sclerosis 8 knock-in mice display slowly progressive motor behavior defects accompanying ER stress and autophagic response. Human Molecular Genetics ; 24(22):6515-29.
TECHNICIANS
Evelyn Huaman
evelyn.huaman2 [at] mcgill.ca
I am helping with managing the lab in its day to day organization, and I contribute to lab activities by running regular mycoplasma tests, genotyping experiments and any other necessary task.
List of publications
UNDERGRADUATE STUDENTS
Jialun Li
jialun.li [at] mail.mcgill.ca
Jonas Julius Mayo
jonas.mayo [at] mail.mcgill.ca
Emily Cha
nayoung.cha [at] mail.mcgill.ca
Hanning Shi
hanning.shi [at] mail.mcgill.ca
