Mathieu Flamand is an assistant professor in the Department of psychiatry and neurosciences in the Faculty of Medicine at Université Laval. He obtained his PhD in Biochemistry from McGill University in 2017, where he studied the mechanistic basis of gene regulation by microRNAs and RNA binding proteins (RBPs). As a Canadian Institutes of Health Research (CIHR) postdoctoral fellow, he then joined Kate Meyer’s group (Department of Biochemistry, Duke University School of Medicine, USA), where his work aimed at understanding the role of RNA modifications in neuronal function. Notably, his research revealed a new role for N6-methyladenosine (m6A), the most abundant RNA modification, in promoting the localization of mRNAs to the dendrites and axons of neurons, a process essential to synaptic plasticity and memory formation. Moreover, he developed novel genomic tools to study binding events of multiple RBPs in cells. In 2023, he joined the Neurosciences Axis at the CRCHU de Québec, where his team works on the fundamental roles of RNA-binding proteins (RBPs) and RNA modifications in synaptic plasticity and in neurodegenerative diseases.

 

Characterize protein-protein and protein-RNA interaction networks at synapses.

In neurons, the local translation of mRNAs is an essential process enabling rapid changes in local protein levels following synaptic transmission events, and which enables in memory formation. RBPs are central players in large regulatory networks which control mRNA transport, decay, and local translation. As such, the loss and mutation of RBPs are linked to a wide range of neurological disorders. To understand the function of these proteins on synaptic plasticity and memory formation, it is crucial to characterize the interaction networks localized at synapses. To this end, Mathieu Flamand’s team employs cutting-edge biochemical, proteomic, and cellular imaging techniques to characterize RBP interactions and function at synapses, using both cultured neurons and mouse models.

 

Understanding the disruption of m6A regulatory networks in neurodegenerative diseases.

Increasing evidence indicates that m6A and m6A-readers are essential to synaptic function. Moreover, disturbances in m6A levels are linked to neurodegenerative disorders leading to memory impairment, including amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD). However, the molecular mechanisms by which they contribute to these diseases remain largely unknown. To better understand this problem, Mathieu Flamand’s team aims to understand the cooperative interactions between RBPs, and the alterations to m6A regulatory networks during these diseases. For this, his group uses a combination of molecular biology and genomics tools he developed to probe the targets and regulation of RBPs in cultured neurons, iPSC, and mouse models. These approaches will identify the critical roles of the m6A pathway in ALS and AD, identify new biomarkers, and provide information on the viability of therapeutically targeting of m6A.

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Flamand MN, Tegowski M, Meyer KD

The Proteins of mRNA Modification: Writers, Readers, and Erasers

Journal Article

Annu Rev Biochem, 92 , 2023.

Abstract | Links:

Tegowski M, Flamand MN, Meyer KD

scDART-seq reveals distinct m6A signatures and mRNA methylation heterogeneity in single cells

Journal Article

Mol Cell, 82 (4), 2022.

Abstract | Links:

Flamand MN, Meyer KD

m6A and YTHDF proteins contribute to the localization of select neuronal mRNAs

Journal Article

Nucleic Acids Res, 50 (8), 2022.

Abstract | Links:

Choi SH, Flamand MN, Liu B, Zhu H, Hu M, Wang M, Sewell J, Holley CL, Al-Hashimi HM, Meyer KD

RBM45 is an m6A-binding protein that affects neuronal differentiation and the splicing of a subset of mRNAs

Journal Article

Cell Rep, 40 (9), 2022.

Abstract | Links:

Flamand MN, Ke K, Tamming R, Meyer KD

Single-molecule identification of the target RNAs of different RNA binding proteins simultaneously in cells

Journal Article

Genes Dev, 36 (17-18), 2022.

Abstract | Links:

Mayya VK, Flamand MN, Lambert AM, Jafarnejad SM, Wohlschlegel JA, Sonenberg N, Duchaine TF

microRNA-mediated translation repression through GYF-1 and IFE-4 in C. elegans development

Journal Article

Nucleic Acids Res, 49 (9), 2021.

Abstract | Links:

Lewis A, Berkyurek AC, Greiner A, Sawh AN, Vashisht A, Merrett S, Flamand MN, Wohlschlegel J, Sarov M, Miska EA, Duchaine TF

A Family of Argonaute-Interacting Proteins Gates Nuclear RNAi

Journal Article

Mol Cell, 78 (5), 2020.

Abstract | Links:

Tran AT, Chapman EM, Flamand MN, Yu B, Krempel SJ, Duchaine TF, Eroglu M, Derry WB

MiR-35 buffers apoptosis thresholds in the C. elegans germline by antagonizing both MAPK and core apoptosis pathways

Journal Article

Cell Death Differ, 26 (12), 2019.

Abstract | Links:

Flamand MN, Meyer KD

The epitranscriptome and synaptic plasticity

Journal Article

Curr Opin Neurobiol, 59 , 2019.

Abstract | Links:

Flamand MN, Gan HH, Mayya VK, Gunsalus KC, Duchaine TF

A non-canonical site reveals the cooperative mechanisms of microRNA-mediated silencing

Journal Article

Nucleic Acids Res, 45 (12), 2017.

Abstract | Links:

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Active projects

  • Fonds de démarrage - Nouveau chercheur, from 2023-07-01 to 2027-06-30
  • Functional Characterization of the Synaptic Interactome of m6A Readers, from 2024-04-01 to 2029-03-31
  • Functional Characterization of the Synaptic Interactome of m6A Readers, from 2024-04-01 to 2029-03-31
Data provided by the Université Laval research projects registery