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Benoit Laurent

Professeur, Faculté de médecine et des sciences de la santé

FMSS Dép. de biochimie et de génomique fonction.

Présentation

Sujet de recherche

Aging Process, Neurodegenerative Diseases

Disciplines de recherche

Biochemistry, Cell Biology, Molecular Biology

Mots-clés

Alternative Splicing, RNA Biology, Epigenetics, Chromatin regulation, Methylation, Gene expression, Transcription factors, Neurons, Cell Differentiation, Cell Cycle, Biochemistry, Molecular Biology, -omics techniques (ChIP-seq, RNA-seq, single-cell), Cell culture (stem cells, primary cells,...)

Intérêts de recherche

Aging is the outcome of complex changes in our biological functions that are responsible for the increased risk of chronic diseases. The overarching goal of my lab is to decipher the etiology of aging. We aim to provide important insights into the age-related molecular changes occurring at the level of our cells and tissues, and to identify new strategies for reducing the incidence of diseases during aging.

Recherche clinique

Langues parlées et écrites

Anglais, Français

Diplômes

(2018). (Post-doctorate, Post-doctorate in Epigenetics). Harvard Medical School.

(2010). Functions of the transcription factor Gfi-1B during normal and pathological erythropoiesis (Doctorate, Ph.D. in Hematology). Université René Descartes (Paris V).

(2005). Transcriptional regulation of Gfi-1B expression during erythroid differentiation (Master's Thesis, M.Sc. in Cellular and Molecular Biology of Hematopoietic Cells). Université de Paris VII (Denis Diderot).

(2004). Fas and Fas-L implication in apoptosis regulation in myelodysplasic syndromes (Master's Thesis, M.Sc. in Physiology and Cellular Biology). Université de Poitiers.

(2003). (Bachelor's Honours, B.Sc. in Life Sciences). Université de Poitiers.

Expérience académique

Assistant Professor. (2020-). Université de Sherbrooke. Canada.

Researcher / Principal Investigator. (2018-). Research Centre on Aging, Sherbrooke. Canada.

Adjunct Professor. (2018-2020). Université de Sherbrooke. Canada.

Post-doctoral research fellow. (2010-2018). Harvard Medical School. United States.

Ph.D. student. (2005-2010). Institut Cochin de Génétique Moléculaire. France.

Prix et distinctions

  • (2023) 2020 Future leader in Canadian Brain Research. Brain Canada Foundation. (Prize / Award).
  • (2020) Banting Research Foundation Discovery Award. Banting Research Foundation. (Prize / Award).
  • (2017) Ruth L. Kirschstein National Research Service Award. National Institutes of Health (NIH) (USA). (Prize / Award).
  • (2011) Post-doctoral fellowship. Philippe Foundation (USA). (Prize / Award).
  • (2011) Post-doctoral fellowship. Fondation ARC pour la recherche sur le cancer (France). (Prize / Award).
  • (2010) Post-doctoral fellowship. Sociéte Française d'hématologie (France). (Prize / Award).
  • (2009) PhD fellowship. Fondation ARC pour la recherche sur le cancer (France). (Prize / Award).
  • (2008) PhD fellowship. Ministère de la Recherche (France). (Prize / Award).
  • Prix Louis Forest - Catégorie : Médicine. Chancellerie des Universités de Paris (France). (Prize / Award).

Financement

  • Grant. (Under Review). Principal Investigator. The isoform proteome: a vulnerable point in the safeguard of genomic integrity?. Natural Sciences and Engineering Research Council of Canada (NSERC). Discovery Grants Program. 275 000 $. (2022-2027)
  • Grant. (Under Review). Principal Applicant. An integrated multi-omics approach to understand the choroid plexus across ages. Canadian Institutes of Health Research (CIHR). Project Grant: Fall 2021. 1 295 000 $. (2022-2027)
  • Grant. (Under Review). Principal Applicant. Alzheimer Society - New Investigator Grant Program. Alzheimer Society of Canada. New Investigator Grant program. 200 000 $. (2022-2025)
  • Grant. (Under Review). Principal Investigator. Shaping the immune system by exercise in the elderly. Fonds de recherche du Québec - Nature et technologies (FRQNT). NOVA program. 225 000 $. (2022-2025)
  • Grant. (Awarded). Principal Investigator. RNA splicing and epigenetics in tuning the fate of neurons. Canadian Institutes of Health Research (CIHR). Project Grant: Spring 2019. 711 450 $. (2019-2024)
  • Grant. (Awarded). Principal Investigator. Challenging epigenetic hallmarks of aging in the choroid plexus to improve brain homeostasis. Brain canada. 2020 Future Leaders in Canadian Brain Research. 100 000 $. (2021-2023)
  • Grant. (Awarded). Co-applicant. Development of lipids of nutritional interest for therapeutic purposes against Alzheimer's disease. Région Auvergne-Rhone-Alpes. Pack Ambition INternational 2021. 504 234 $. (2022-2023)
  • Grant. (Awarded). Principal Investigator. Assessing the clinical stages of Alzheimer’s disease: identification of molecular biomarkers in blood cells. Research Center on Aging. Pilot Grant program. 20 000 $. (2021-2022)
  • Grant. (Awarded). Co-investigator. Characterization of the endocannabinoid system in iPSC-derived neurons from individuals with Fragile X syndrome. Research center CHUS Sherbrooke. Pilot Grant program. 25 000 $. (2021-2022)
  • Grant. (Completed). Co-investigator. Choroid plexuses during aging in APOE4 mice: assessing their transcriptome regarding the age and consumption of omega-3 fatty acids. Quebec Network for Research on Aging. Pilot Grant program. 27 000 $. (2019-2020)
  • Grant. (Completed). Principal Investigator. Deciphering the epigenetic regulation of alternative splicing in neurons. Banting Foundation. Banting Research Foundation Discovery Award. 25 000 $. (2019-2020)
  • Grant. (Completed). Co-applicant. Transcriptomic study of the effects of High Intensity Interval Training on monocytes from older women with type 2 diabetes. Fonds de Dotation de la Faculté de Médecine de l'Université de Sherbrooke. Pilot grant program. 10 000 $. (2019-2020)
  • Grant. (Completed). Principal Investigator. Development of a stem cell reprogramming platform: a new way to understand aging-related mechanisms. Research Center on Aging (Sherbrooke). Pilot Grant Program. 75 000 $. (2019-2020)
  • Grant. (Completed). Principal Investigator. Effects of nutrition on choroid plexus in healthy and diseased brain. Institut des nutraceutiques et des aliments fonctionnels (INAF). Projets pilotes 2018-2019. 9 000 $. (2019-2020)

Publications

Articles de revue

  • Husain MA*, Laurent B, Plourde M. (2021). APOE and Alzheimer’s disease: from lipid transport to physiopathology and therapeutics. Frontiers in Neuroscience 15 630502. (Published).
  • Jha DK, Zhang C, Laurent B, Kubaczka C, Missios P, Chapuy B, Morris V, Bhan A, Cote CM, Huang YC, Tan Y, Morse M, Bingham T, Marunde MR, Vaidya A, Gillespie ZB, Howard SA, Rowe G, Jing R, Lumertz-daRocha E, North TE, Dominguez D, Keogh MC, Schlager TM, Shi Y, Li H, Shipp MA, Daley GQ. (2021). Epigenetic rewiring mediated by lysine demethylases sustains anoncogenic transcriptional and signaling state. Cancer Cell N/A N/A. (Revision Requested).
  • Khan MR*, Wellinger RJ, Laurent B. (2021). Exploring the alternative splicing of long non-coding RNAs. Trends in Genetics 37 (8), 695-698. (Published).
  • Munawara U, Catanzaro M, Xu W, Tan C, Hirokawa K, Bosco N, Dumoulin D, Khalil A, Larbi A, Lévesque S, Ramassamy C, Barron AE, Cunnane S, Beauregard PB, Bellenger JP, Rodrigues S, Desroches M, Witkowski JM, Laurent B, Frost EH, Fulop T. (2021). Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease. Immun Ageing 18 (1), 29. (Published).
  • Pifferi F, Laurent B, Plourde M. (2021). Lipid transport and metabolism at the blood-brain interface: implications in health and disease. Frontiers in Physiology 12 645646. (Published).
  • Kaiser K, Jang A, Lun MP, Procházka J, Machoň O, Procházková M, Laurent B, Gyllborg D, van Amerongen R, Kompaníková P, Wu F, Barker RA, Uramová I, Sedláček R, Kozmík Z, Arenas E, Lehtinen MK, Bryja V. (2021). MEIS-WNT5A axis regulates development of fourth ventricle choroid plexus. Development 148 (10), dev192054. (Published).
  • Fulop T, Tripathi S, Rodrigues S, Desroches M, Bunt T, Eiser A, Bernier F, Beauregard PB, Barron AE, Khalil A, Plotka A, Hirokawa K, Larbi A, Bocti C, Laurent B, Frost EH, Witkowski JM. (2021). Targeting impaired antimicrobial immunity in the brain for the treatment of Alzheimer's disease. Neuropsychiatr Dis Treat. 17 1311-1339. (Published).
  • Hamelin Morrissette J, Tremblay D, Marcotte-Chénard A, Lizotte F, Brunet MA, Laurent B, Riesco E, Geraldes P. (2021). Transcriptomic modulation in response to High-Intensity Interval Training in monocytes of older women with type 2 diabetes. Journal of Applied Physiology N/A (N/A), N/A. (Submitted).
  • Chen HY, Wang ML, Laurent B, Hsu CH, Chen MT, Lin LT, Shen J, Chang WC, Hsu J, Hung MC, Chen YW, Huang PI, Yang YP, Li CP, Ma HI, Chen CH, Lin WC, Chiou SH. (2020). Musashi-1 promotes stress-induced tumor progression through recruitment of AGO2. Theranostics 10 (1), 201-217. (Published).
  • Tsai PH**, Chien Y**, Wang ML**, Hsu CH**, Laurent B**, Chou SJ, Chang WC, Chien CS, Li HY, Lee HC, Huo TI, Hung JH, Chen CH, Chiou SH **co-authorship. (2019). Ash2l interacts with Oct4-stemness circuitry to promote super-enhancer-driven pluripotency network. Nucleic Acid Research 47 (19), 10115-10133. (Accepted).
  • Guo J, Zhang J, Laurent B, Dai X, Gan W, Liu P, Guo A, Yuan M, Asara JM, Shi Y, Pandolfi PP, Wei W. (2018). Akt methylation by SETDB1 promotes Akt kinase activity and oncogenic functions. Nature Cell Biology 21 (2), 226-237. (Published).
  • Chau KF*, Shannon ML, Fame RM, Fonseca E, Mullan H, Johnson MB, Sendamarai AK, Springel MW, Laurent B, Lehtinen MK. (2018). Downregulation of ribosome biogenesis during early forebrain development. eLife 7 (pii), e36998. (Published).
  • Iberg-Badeaux A, Collombet S, Laurent B, van Oevelen C, Chin KK, Thieffry D, Graf T, Shi Y. (2017). A Transcription Factor Pulse Can Prime Chromatin for Heritable Transcriptional Memory. Molecular and Cellular Biology 37 (4), e00372-16. (Published).
  • Chen HY, Lin LT, Wang ML, Laurent B, Hsu CH, Pan CM, Jiang WR, Chen PY, Ma HI, Chen YW, Huang PI, Chiou A, Chiou SH. (2017). Musashi-1 Enhances Glioblastoma Cell Migration and Cytoskeletal Dynamics through Translational Inhibition of Tensin3. Scientific Reports 7 (1), 8710. (Published).
  • Xiang Y**, Laurent B**, Hsu CH**, Nachtergaele S, Lu Z, Sheng W, Xu C*, Chen H, Ouyang J, Wang S, Ling D, Hsu PH, Zou L, Jambhekar A, He C, Shi Y. **co-authorship. (2017). RNA m6A methylation regulates the ultraviolet-induced DNA damage response. Nature 543 (7646), 573-576. (Published).
  • Laurent B, Ruitu L, Murn J, Hempel K, Ferrao R, Xiang Y, Liu S, Garcia BA, Wu H, Wu F, Steen H, Shi Y. (2015). A specific LSD1/KDM1A isoform regulates neuronal differentiation through H3K9 demethylation. Molecular Cell 57 (6), 957-70. (Published).
  • Chen M, Zhu N, Liu X, Laurent B, Tang Z, Eng R, Shi Y, Armstrong SA, Roeder RG. (2015). JMJD1C is required for the survival of acute myeloid leukemia by functioning as a coactivator for key transcription factors. Genes & Development 29 (20), 2123-39. (Published).
  • Brookes E, Laurent B, Õunap K, Carroll R, Moeschler JB, Field M, Schwartz CE, Gecz J, Shi Y. (2015). Mutations in the intellectual disability gene KDM5C reduce protein stability and demethylase activity. Human Molecular Genetics 24 (10), 2861-72. (Published).
  • Mosammaparast N, Kim H, Laurent B, Zhao Y, Lim HJ, Majid MC, Dango S, Luo Y, Hempel K, Sowa ME, Gygi SP, Steen H, Harper JW, Yankner B, Shi Y. (2013). The histone demethylase LSD1/KDM1A promotes the DNA damage response. Journal of Cell Biology 203 (3), 457-70. (Published).
  • Laurent B, Randrianarison-Huetz V, Frisan E, Andrieu-Soler C, Soler E, Fontenay M, Dusanter-Fourt I, Duménil D. (2012). A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain. Journal of Cell Science 125 (4), 993-1002. (Published).
  • Randrianarison-Huetz V**, Laurent B**, Bardet V, Blobe GC, Huetz F, Duménil D **co-authorship. (2010). Gfi-1B controls human erythroid and megakaryocytic differentiation by regulating TGF-beta signaling at the bipotent erythro-megakaryocytic progenitor stage. Blood 115 (14), 2784-95. (Published).
  • Laurent B, Randrianarison-Huetz V, Maréchal V, Mayeux P, Dusanter-Fourt I, Duménil D. (2010). High-mobility group protein HMGB2 regulates human erythroid differentiation through trans-activation of GFI1B transcription. Blood 115 (3), 687-95. (Published).
  • Laurent B, Randrianarison-Huetz V, Kadri Z, Roméo PH, Porteu F, Duménil D. (2009). Gfi-1B promoter remains associated with active chromatin marks throughout erythroid differentiation of human primary progenitor cells. Stem Cells 27 (9), 2153-62. (Published).
  • Laurent B, Randrianarison V, Duménil D. (2006). The family of Gfi-1 zinc finger transcriptional repressor oncoproteins in hematopoiesis regulation. Hématologie 12 (6), 379-388. (Published).

Chapitres de livre

  • Laurent B, Shi Y. (2016). Expression, Purification, and Biochemical Analysis of the LSD1/KDM1A Histone Demethylase. Ronen Marmorstein. Methods in Enzymology - Enzymes of Epigenetics (573, 241-59). United States : Elsevier Inc. (Published).

Articles de conférence

  • Bavykina V*, Brunet MA, Husain MA*, Parent-Roberge H, Zimmer A, Khalil A, Fülöp T, Laurent B. (2021). Assessing theclinical stages of Alzheimer’s disease by the identification of RNA biomarkers in blood cells. New Horizons in Alzheimer's Disease. (Submitted).
  • Bavykina V*, Brunet MA, Husain MA*, Parent-Roberge H, Zimmer A, Khalil A, Fülöp T, Laurent B. (2021). Assessing theclinical stages of Alzheimer’s disease by the identification of RNA biomarkers in blood cells. RiboClub annual meeting. (Submitted).
  • Avila Lopez J*, Brunet MA, St-Germain J*, Avino M, Husain MA*, Rocha J*, Champagne D, Miard S, Picard F, Fernandes K, Plourde M, Laurent B. (2021). Transcriptomic study of the choroid plexus during aging. RiboClub annual meeting. (Submitted).
  • Avila Lopez J*, Brunet MA, St-Germain J*, Avino M, Husain MA*, Rocha J*, Champagne D, Miard S, Picard F, Plourde M, Laurent B. (2021). Transcriptomic study of the choroid plexus during aging. TREnD conference (Toronto RNA Enthusiasts' day). (Accepted).
  • Rocha J*, Brunet MA, St-Germain J*, Avila Lopez J*, Miard S, Picard F, Plourde M, Laurent B. (2020). Age-related changes in the transcriptomic signature of the adult mouse choroid plexus. Conference "Cerebral Fluid Flow and Function: Lymphatics, Glymphatics and the Choroid Plexus". (Accepted).
  • Rocha J*, Brunet MA, St-Germain J*, Avila Lopez J*, Miard S, Picard F, Plourde M, Laurent B. (2019). Age-related changes in the transcriptomic signature of the adult mouse choroid plexus. International Symposium “Biology of Aging: Understanding aging to better intervene”. (Accepted).
  • Rocha J*, Brunet MA, St-Germain J*, Avila Lopez J*, Miard S, Picard F, Plourde M, Laurent B. (2019). Age-related changes in the transcriptomic signature of the adult mouse choroid plexus. RiboClub Annual Meeting. (Accepted).
  • Tremblay D, Marcotte-Chénard A, Mony MM, Boulay P, Brochu M, Dionne IJ, Langlois MF, Tessier D, Laurent B, Geraldes P, Riesco E. (2019). Whole-genome transcriptomic analysis of training-induced changes inmonocytes of elderly women with type 2 diabetes. Canadian Society of Exercise Physiology (CSEP). (Accepted).
  • Jha DK, Laurent B, Zhang C, Kubaczka C, Chapuy B, Sousa P, Missios P, Robert Grant Rowe, Chung-Huang Y, Tan Y, Barragan J, North T, Schlager T, Li H, Shi Y, Shipp M, Daley GQ. (2018). Novel epigenetic vulnerabilities for diffuse large B-cell lymphoma. Blood, (Published).
  • Xiang Y**, Laurent B**, Hsu CH**, Nachtergaele S, Lu Z, Sheng W, Xu C*, Chen H, Ouyang J, Wang S, Ling D, Hsu PH, Zou L, Jambhekar A, He C, Shi Y **co-authorship. (2017). RNA m6A methylation regulates the UV-induced DNA damage response. Dr. M. Judah Folkman Research Day. (Accepted).
  • Xiang Y**, Laurent B**, Hsu CH**, Nachtergaele S, Lu Z, Sheng W, Xu C*, Chen H, Ouyang J, Wang S, Ling D, Hsu PH, Zou L, Jambhekar A, He C, Shi Y **co-authorship. (2017). RNA m6A methylation regulates the UV-induced DNA damage response. “Hallmarks of Cancer: Focus on RNA” symposium. (Accepted).
  • Xiang Y**, Laurent B**, Hsu CH**, Nachtergaele S, Lu Z, Sheng W, Xu C*, Chen H, Ouyang J, Wang S, Ling D, Hsu PH, Zou L, Jambhekar A, He C, Shi Y **co-authorship. (2017). RNA m6A methylation regulates the UV-induced DNA damage response. “Genome rearrangements and mutation signatures in development and cancer” conference. (Accepted).
  • Xiang Y**, Laurent B**, Hsu CH**, Nachtergaele S, Lu Z, Sheng W, Xu C*, Chen H, Ouyang J, Wang S, Ling D, Hsu PH, Zou L, Jambhekar A, He C, Shi Y **co-authorship. (2016). RNA m6A methylation regulates the UV-induced DNA damage response. Functional RNAs - Cell Symposia. (Accepted).
  • Xiang Y**, Laurent B**, Hsu CH**, Nachtergaele S, Lu Z, Sheng W, Xu C*, Chen H, Ouyang J, Wang S, Ling D, Hsu PH, Zou L, Jambhekar A, He C, Shi Y **co-authorship. (2016). RNA m6A methylation regulates the UV-induced DNA damage response. RiboClub Annual Meeting. (Accepted).
  • Laurent B, Ruitu L, Murn J, Hempel K, Ferrao R, Xiang Y, Liu S, Garcia BA, Wu H, Wu F, Steen H, Shi Y. (2015). A specific LSD1/KDM1A isoform regulates neuronal differentiation through H3K9 demethylation. Dr. M. Judah Folkman Research Day. (Accepted).
  • Laurent B, Ruitu L, Murn J, Hempel K, Ferrao R, Xiang Y, Liu S, Garcia BA, Wu H, Wu F, Steen H, Shi Y. (2015). A specific LSD1/KDM1A isoform regulates neuronal differentiation through H3K9 demethylation. Keystone Symposia "Neuroepigenetics". (Accepted).

Autres contributions

Activités de collaboration internationale

  • PI. France. Collaboration with the laboratory of Dr Fabien Pifferi (Museum National d'Histoire Naturelle, Brunoy) on the aging of the choroid plexus in primates (microcebus animal model).
  • PI. France. Collaboration with the laboratory of Dr Homaira Nawabi (Institut des Neurosciences, Grenoble) on the molecular mechanisms underlying axon regeneration.
  • PI. United Kingdom. Collaboration with the laboratory of Dr Jernej Ule (The Francis Crick Institute, London) on the role of Alu repetitive elements in regulating alternative splicing in neurons.
  • PI. United States. Collaboration with the laboratory of Pr Maria Lehtinen (Harvard Medical School, Boston) on the molecular mechanisms involved in the development of the choroid plexus.

Présentations

  • (2021). Aging of the choroid plexus-csf system: making the old new again?. Brain Barriers - Cold Spring Harbor Laboratory Meeting. Cold Spring Harbor, United States
  • (2021). Regulation of alternative splicing during neuronal differentiation. 88th Acfas conference. Sherbrooke, Canada
  • (2019). Aging and nutrient-sensing of the choroid plexus-CSF system. Workshop - New frontiers in the brain: unexpected roles of the choroid plexus-cerebrospinal fluid system in health and disease. West Sussex, United Kingdom
  • (2019). Epigenetic regulation and alternative splicing: a way to control cell fate. 8th DOCC scientific day - Diabetes, Obesity & Cardiovascular Complications. Sherbrooke, Canada
  • (2017). Epigenetics and RNA dynamics in regulating cell fate. Institut des Neurosciences. Grenoble, France
  • (2017). Epigenetics and RNA dynamics in regulating cell fate. Brain Center Rudolf Magnus, University Medical Center Utrecht. Utrecht, Netherlands
  • (2017). Epigenetics and RNA dynamics in regulating cell fate. Department of Biochemistry, Fudan University. Shanghai, China
  • (2017). RNA m6A methylation regulates the UV-induced DNA damage response. "Hallmarks of Cancer: Focus on RNA” symposium. Prague, Czech Republic
  • (2017). RNA methylation and DNA damage repair. Dr. M. Judah Folkman Research Day. Boston, United States
  • (2017). RNA methylation and DNA damage repair. “Genome rearrangements and mutation signatures in development and cancer” conference. Boston, United States
  • (2016). RNA m6A methylation regulates the UV-induced DNA damage response. Functional RNAs - Cell Symposia. Guangzhou, China
  • (2010). A short Gfi-1B isoform controls erythroid differentiation by recruiting the LSD1-CoREST complex through the dimethylation of its SNAG domain. Congress of French Society of Hematology, March 18-20. Paris, France
  • (2009). HMGB2 protein regulates human erythroid development through the control of Gfi-1B expression. Hematopoiesis & Oncogenesis Congress, Sept 30 - Oct 3, Presqu’île de Giens, France. France
  • (2009). Repression by Gfi-1B depends on methylation of its isoform during erythropoiesis. FASEB Summer Conference “Epigenetics, chromatin & transcription”, July 12-17, Snowmass, USA. United States
  • (2008). Epigenetic mechanisms of Gfi-1B transcription during erythropoiesis. Congress of French Society of Hematology, March 20-22, Paris, France. France
  • (2006). Transcriptional regulation of Gfi-1B by GATA-1/Oct-1/Gfi-1B complex. Hematopoiesis & Oncogenesis Congress, October 1-4, Presqu’île de Giens, France. France