Paul Dutchak

Paul Dutchak,
M.Sc., Ph.D.

Assistant Professor
Département de psychiatrie et de neurosciences, Faculté de Médecine


Investigating Neurometabolic Pathways involved in Brain Health and Disease.

Dr. Paul Dutchak's research program aims to understand the metabolic requirements for normal brain function and determine how genetic changes effect the regulation of metabolic pathways in the brain.  Dr. Dutchak is particularly interested in developing a metabolic map of neurological disorders to better diagnose, and therapeutically target neurological diseases that are underscored by a dysregulation of metabolism, including: epilepsy, autism and tuberous sclerosis.  

Dr. Dutchak's lab is currently studying an evolutionarily conserved amino acid sensing complex called GATOR1.  Genetic mutations in this complex are associated with epilespy, autism and cancer in humans. 

*Dr. Dutchak is currently looking for graduate students and post doctoral researchers to fill available positions in the lab. Only eligible and serious candidates will be considered.


Current: 

  • Maéline Muller
  • Imane Hadj-Aissa
  • Pauline Gelon
  • Jasmine Bélanger
  • Maria Del Carmen Pelaez Brenes

Previous:

  • Conghao (Tony) Zhang (NSERC URSA; 2021)
  • Alisson Skelling (2021)
  • Jeremy Hui (NSERC URSA; 2019)
  • Janani Venkatasubramani (2019-2021)

GATOR1 Mutations Impair PI3 Kinase-Dependent Growth Factor Signaling Regulation of mTORC1. Muller, M.; Bélanger, J.; Hadj-Aissa, I.; Zhang, C.; Sephton, C.F.; Dutchak, P.A.  Int. J. Mol. Sci. 2024, 25, 2068. https://doi.org/10.3390/ijms25042068

Antisense oligonucleotides targeting the miR-29b binding site in the GRN mRNA increase progranulin translation. Aggarwal, G., Banerjee, S., Jones, S. A., Benchaar, Y., Bélanger, J., Sévigny, M., Smith, D. M., Niehoff, M. L., Pavlack, M., de Vera, I. M. S., Petkau, T. L., Leavitt, B. R., Ling, K., Jafar-Nejad, P., Rigo, F., Morley, J. E., Farr, S. A., Dutchak, P. A., Sephton, C. F., & Nguyen, A. D. J Biol Chem. (2023); 299 (12):105475. doi:10.1016/j.jbc.2023.105475

Neuronal dysfunction caused by FUSR521G promotes ALS-associated phenotypes that are attenuated by NF-κB inhibition. Pelaez, M. C., Desmeules, A., Gelon, P. A., Glasson, B., Marcadet, L., Rodgers, A., Phaneuf, D., Pozzi, S., Dutchak, P. A., Julien, J. P., & Sephton, C. F. Acta Neuropathol Commun. (2023);11(1):182. Published 2023 Nov 16. doi:10.1186/s40478-023-01671-1

Synaptic dysfunction in ALS and FTD: anatomical and molecular changes provide insights into mechanisms of disease Gelon PA, Dutchak PA and Sephton CF (2022)  Front. Mol. Neurosci. 15:1000183. doi: 10.3389/fnmol.2022.1000183

NPRL2 Inhibition of mTORC1 Controls Sodium Channel Expression and Brain Amino Acid Homeostasis. Jeremy B. Hui, Jose Cesar Hernandez Silva, Mari Carmen Pelaez, Myriam Sévigny, Janani Priya Venkatasubramani, Quentin Plumereau, Mohamed Chahine, Christophe D. Proulx, Chantelle F. Sephton and Paul A. Dutchak.  eNeuro. 14 February 2022, ENEURO.0317-21.2022; DOI: https://doi.org/10.1523/ENEURO.0317-21.2022

A postzygotic de novo NCDN mutation identified in a sporadic FTLD patient results in neurochondrin haploinsufficiency and altered FUS granule dynamics. Gaël Nicolas, Myriam Sévigny, François Lecoquierre, Florent Marguet, Andréanne Deschênes, Maria Carment del Pelaez, Sébastien Feuillette, Anaïs Audebrand, Magalie Lecourtois, Stéphane Rousseau, Anne-Claire Richard, Kévin Cassinari, Vincent Deramecourt, Charles Duyckaerts, Anne Boland, Jean-François Deleuze, Vincent Meyer, Jordi Clarimon Echavarria, Ellen Gelpi, Haruhiko Akiyama, Masato Hasegawa, Ito Kawakami, Tsz H. Wong, Jeroen G. J. Van Rooij, John C. Van Swieten, Dominique Campion, Paul A. Dutchak, David Wallon, Flavie Lavoie-Cardinal, Annie Laquerrière, Anne Rovelet-Lecrux & Chantelle F. Sephton.  Acta Neuropathol Commun 10, 20 (2022).

Antisense oligonucleotide-based therapeutic strategy for progranulin-deficient frontotemporal dementia Geetika Aggarwal, Subhashis Banerjee, Spencer A. Jones, Monica Pavlack, Yousri Benchaar, Jasmine Bélanger, Myriam Sévigny, Denise M. Smith, Michael L. Niehoff, Ian Mitchelle S. de Vera, Terri L. Petkau, Blair R. Leavitt, Karen Ling, Paymaan Jafar-Nejad, Frank Rigo, John E. Morley, Susan A. Farr, Paul A. Dutchak, Chantelle F. Sephton, Andrew D. Nguyen (2022) BioRxiv doi:10.1101/2022.01.12.476053

FUS contributes to mTOR-dependent inhibition of translation M Sévigny, IB Julien, JP Venkatasubramani, JB Hui, PA Dutchak, CF Sephton (2020) Journal of Biological Chemistry 295 (52), 18459-18473

Metabolic Networks Influencing Skeletal Muscle Fiber Composition. Bourdeau Julien I, Sephton CF, Dutchak PA. (2018) Front. Cell Dev. Biol. 6:125. doi:10.3389/fcell.2018.00125

Loss of a Negative Regulator of mTORC1 Induces Aerobic Glycolysis and Altered Fiber Composition in Skeletal Muscle. Dutchak PA, Estill-Terpack SJ, Plec AA, ... Deberardinis RJ, Yu Y, Tu BP. Cell Rep. 2018 May 15, 23(7): 1907–1914. doi: 10.1016/j.celrep.2018.04.058

Altering cellular differentiation and energy metabolism by the mTORC1 inhibitor NPRL2. Dutchak PA, Estill SJ, Tu BP. Mol Cancer Res April 1 2016 (14) doi:10.1158/1557-3125.DEVBIOLCA15-B08

Regulation of Hematopoiesis and Methionine Homeostasis by mTORC1 Inhibitor NPRL2. Dutchak PA, Laxman S, Estill SJ, Wang C, Wang Y, Wang Y, Bulut GB, Gao J, Huang LJ, Tu BP. Cell Rep. 2015 Jul 21;12(3):371-9. doi:10.1016/j.celrep.2015.06.042. Epub 2015 Jul 9. PMID:26166573

Fibroblast growth factor-21 regulates PPARγ activity and the antidiabetic actions of thiazolidinediones. Dutchak PA, Katafuchi T, Bookout AL, Choi JH, Yu RT, Mangelsdorf DJ, Kliewer SA. Cell. 2012 Feb 3;148(3):556-67. doi:10.1016/j.cell.2011.11.062. PMID:22304921

Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor γ. Wei W, Dutchak PA, Wang X, Ding X, Wang X, Bookout AL, Goetz R, Mohammadi M, Gerard RD, Dechow PC, Mangelsdorf DJ, Kliewer SA, Wan Y. Proc Natl Acad Sci U S A. 2012 Feb 21;109(8):3143-8. doi: 10.1073/pnas.1200797109. Epub 2012 Feb 6. PMID:22315431

Endocrine regulation of the fasting response by PPARalpha-mediated induction of fibroblast growth factor 21. Inagaki T, Dutchak P, Zhao G, Ding X, Gautron L, Parameswara V, Li Y, Goetz R, Mohammadi M, Esser V, Elmquist JK, Gerard RD, Burgess SC, Hammer RE, Mangelsdorf DJ, Kliewer SA. Cell Metab. 2007 Jun;5(6):415-25.PMID:17550777


  • Bachelor of Science (B.Sc.): University of Saskatchewan, Department of Biochemistry
  • Master of Science (M.Sc.): University of Saskatchewan, Department of Biochemistry
  • Doctorate of Philosophy (Ph.D.): University of Texas Southwestern Medical Center at Dallas
  • Post-doctoral Fellow: University of Texas Southwestern Medical Center at Dallas

2023-25 Brain Canada - Future Leaders Award

2023-24 Rare Diseases Models and Mechanisms Network Grant (CIHR, Genome Canada and Le Grand défi Pierre Lavoie)

2020-24 FRQS Junior 1 Award

2019-20 Tuberous Sclerosis Alliance - Project Grant

2018-25 Natural Sciences and Engineering Research Council (NSERC/CRSNG) - Discovery Grant

2018-19 Natural Sciences and Engineering Research Council (NSERC/CRSNG) - Discovery Launch Grant

2014-16 Cancer Prevention Research Institute of Texas -Training Grant


Keywords: 

metabolism, cell signaling, translation, epilepsy, neurodegeneration



 
 
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2601 Chemin de la Canardière
Québec (Québec)
G1J 2G3
Canada


Office: 
F-3516

 

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