Portrait de Sébastien Lemieux

Sébastien Lemieux

Membre académique associé
Professeur associé, Université de Montréal, Département d'informatique et de recherche opérationnelle et Département de biochimie et de médecine moléculaire
Sujets de recherche
Biologie computationnelle
Modélisation moléculaire
Site web
Google Scholar
LinkedIn

Biographie

Microbiologiste de formation, Sébastien Lemieux s'est tourné vers la bio-informatique en 1997 et a réalisé des études de maîtrise et de doctorat à l'Université de Montréal sous la direction de François Major. Après avoir obtenu son doctorat en 2002, le jeune chercheur s'est dirigé vers le secteur privé et a effectué un stage postdoctoral chez Elitra Canada (maintenant Merck & Co.) sous la supervision de Bo Jiang. Il y a acquis des compétences en analyse de séquences et en analyse de données de microréseaux d'ADN, ainsi qu'en intégration informatique de données expérimentales.

Il a finalement rejoint les rangs de l'Institut de recherche en immunologie et en cancérologie (IRIC) en 2005. En 2018, il a été nommé professeur agrégé au Département de biochimie et médecine moléculaire de la Faculté de médecine de l'Université de Montréal.

Étudiants actuels

Léa Kaufmann
Maîtrise recherche - UdeM
Site web
Github
Matthew Scicluna
Doctorat - UdeM
Superviseur⋅e principal⋅e :
Julie Hussin
Github
Google Scholar

Publications

Proteogenomics and Differential Ion Mobility Enable the Exploration of the Mutational Landscape in Colon Cancer Cells
Zhaoguan Wu
Eric Bonneil
Michael Belford
Cornelia Boeser
Maria-Virginia Ruiz Cuevas
Sébastien Lemieux
Jean-Jacques Dunyach
Pierre Thibault
2022-08-22
Analytical Chemistry (publié)
doi.org
Two types of human TCR differentially regulate reactivity to self and non-self antigens
Assya Trofimov
Philippe Brouillard
Jean-David Larouche
Jonathan Séguin
Jean-Philippe Laverdure
Ann Brasey
Grégory Ehx
Denis-Claude Roy
Lambert Busque
Silvy Lachance
Sébastien Lemieux
Claude Perreault
2022-08-17
iScience (publié)
doi.org
Induced pluripotent stem cells display a distinct set of MHC I-associated peptides shared by human cancers
Anca Apavaloaei
Leslie Hesnard
Marie-Pierre Hardy
Basma Benabdallah
Grégory Ehx
Catherine Thériault
Jean-Philippe Laverdure
Chantal Durette
Joël Lanoix
Mathieu Courcelles
Nandita Noronha
Kapil Dev Chauhan
Sébastien Lemieux
Christian Beauséjour
Mick Bhatia
Pierre Thibault
Claude Perreault
2022-08-01
Cell Reports (publié)
doi.org
Two types of human TCR differentially regulate reactivity to self and non-self antigens
Assya Trofimov
Philippe Brouillard
Jean-David Larouche
Jonathan Y. Séguin
Jean-Philippe Laverdure
A. Brasey
Grégory Ehx
D. Roy
Lambert Busque
Silvy Lachance
Sébastien Lemieux
Claude Perreault
2022-04-28
bioRxiv (preprint)
doi.org
Monoallelic Heb/Tcf12 Deletion Reduces the Requirement for NOTCH1 Hyperactivation in T-Cell Acute Lymphoblastic Leukemia
Diogo F. T. Veiga
Mathieu Tremblay
Bastien Gerby
Sabine Herblot
André Haman
Patrick Gendron
Sébastien Lemieux
Juan Carlos Zúñiga-Pflücker
Josée Hébert
Joseph Paul Cohen
Trang Hoang
Early T-cell development is precisely controlled by E proteins, that indistinguishably include HEB/TCF12 and E2A/TCF3 transcription factors,… (voir plus) together with NOTCH1 and pre-T cell receptor (TCR) signalling. Importantly, perturbations of early T-cell regulatory networks are implicated in leukemogenesis. NOTCH1 gain of function mutations invariably lead to T-cell acute lymphoblastic leukemia (T-ALL), whereas inhibition of E proteins accelerates leukemogenesis. Thus, NOTCH1, pre-TCR, E2A and HEB functions are intertwined, but how these pathways contribute individually or synergistically to leukemogenesis remain to be documented. To directly address these questions, we leveraged Cd3e-deficient mice in which pre-TCR signaling and progression through β-selection is abrogated to dissect and decouple the roles of pre-TCR, NOTCH1, E2A and HEB in SCL/TAL1-induced T-ALL, via the use of Notch1 gain of function transgenic (Notch1ICtg) and Tcf12+/- or Tcf3+/- heterozygote mice. As a result, we now provide evidence that both HEB and E2A restrain cell proliferation at the β-selection checkpoint while the clonal expansion of SCL-LMO1-induced pre-leukemic stem cells in T-ALL is uniquely dependent on Tcf12 gene dosage. At the molecular level, HEB protein levels are decreased via proteasomal degradation at the leukemic stage, pointing to a reversible loss of function mechanism. Moreover, in SCL-LMO1-induced T-ALL, loss of one Tcf12 allele is sufficient to bypass pre-TCR signaling which is required for Notch1 gain of function mutations and for progression to T-ALL. In contrast, Tcf12 monoallelic deletion does not accelerate Notch1IC-induced T-ALL, indicating that Tcf12 and Notch1 operate in the same pathway. Finally, we identify a tumor suppressor gene set downstream of HEB, exhibiting significantly lower expression levels in pediatric T-ALL compared to B-ALL and brain cancer samples, the three most frequent pediatric cancers. In summary, our results indicate a tumor suppressor function of HEB/TCF12 in T-ALL to mitigate cell proliferation controlled by NOTCH1 in pre-leukemic stem cells and prevent NOTCH1-driven progression to T-ALL.
2022-03-24
Frontiers in Immunology (publié)
doi.org
Monoallelic Heb/Tcf12 Deletion Reduces the Requirement for NOTCH1 Hyperactivation in T-Cell Acute Lymphoblastic Leukemia
Diogo F. T. Veiga
Mathieu R. Tremblay
Bastien Gerby
Sabine Herblot
André Haman
Patrick Gendron
Sébastien Lemieux
J. Zúñiga-Pflücker
Josée Hébert
Joseph Paul Cohen
T. Hoang
Early T-cell development is precisely controlled by E proteins, that indistinguishably include HEB/TCF12 and E2A/TCF3 transcription factors,… (voir plus) together with NOTCH1 and pre-T cell receptor (TCR) signalling. Importantly, perturbations of early T-cell regulatory networks are implicated in leukemogenesis. NOTCH1 gain of function mutations invariably lead to T-cell acute lymphoblastic leukemia (T-ALL), whereas inhibition of E proteins accelerates leukemogenesis. Thus, NOTCH1, pre-TCR, E2A and HEB functions are intertwined, but how these pathways contribute individually or synergistically to leukemogenesis remain to be documented. To directly address these questions, we leveraged Cd3e-deficient mice in which pre-TCR signaling and progression through β-selection is abrogated to dissect and decouple the roles of pre-TCR, NOTCH1, E2A and HEB in SCL/TAL1-induced T-ALL, via the use of Notch1 gain of function transgenic (Notch1ICtg) and Tcf12+/- or Tcf3+/- heterozygote mice. As a result, we now provide evidence that both HEB and E2A restrain cell proliferation at the β-selection checkpoint while the clonal expansion of SCL-LMO1-induced pre-leukemic stem cells in T-ALL is uniquely dependent on Tcf12 gene dosage. At the molecular level, HEB protein levels are decreased via proteasomal degradation at the leukemic stage, pointing to a reversible loss of function mechanism. Moreover, in SCL-LMO1-induced T-ALL, loss of one Tcf12 allele is sufficient to bypass pre-TCR signaling which is required for Notch1 gain of function mutations and for progression to T-ALL. In contrast, Tcf12 monoallelic deletion does not accelerate Notch1IC-induced T-ALL, indicating that Tcf12 and Notch1 operate in the same pathway. Finally, we identify a tumor suppressor gene set downstream of HEB, exhibiting significantly lower expression levels in pediatric T-ALL compared to B-ALL and brain cancer samples, the three most frequent pediatric cancers. In summary, our results indicate a tumor suppressor function of HEB/TCF12 in T-ALL to mitigate cell proliferation controlled by NOTCH1 in pre-leukemic stem cells and prevent NOTCH1-driven progression to T-ALL.
2022-03-24
Frontiers in Immunology (published)
doi.org
Vesicular trafficking is a key determinant of the statin response in acute myeloid leukemia
Jana K Krosl
Marie-Eve Bordeleau
Céline Moison
Tara MacRae
Isabel Boivin
Nadine Mayotte
Deanne Gracias
Irène Baccelli
Vincent-Philippe Lavallee
Richard Bisaillon
Bernhard Lehnertz
Rodrigo Mendoza-Sanchez
Réjean Ruel
Thierry Bertomeu
Jasmin Coulombe-Huntington
Geneviève Boucher
Nandita Noronha
C. Pabst
M. Tyers
Patrick Gendron … (voir 5 de plus)
Sébastien Lemieux
Frederic Barabe
Anne Marinier
Josée Hébert
Guy Sauvageau
Key Points Inhibition of RAB protein function mediates the anti–acute myeloid leukemia activity of statins. Statin sensitivity is associat… (voir plus)ed with enhanced vesicle-mediated traffic.
2021-11-03
Blood Advances (published)
doi.org
Vesicular trafficking is a key determinant of the statin response in acute myeloid leukemia
Jana Krosl
Marie-Eve Bordeleau
Céline Moison
Tara MacRae
Isabel Boivin
Nadine Mayotte
Deanne Gracias
Irène Baccelli
Vincent-Philippe Lavallee
Richard Bisaillon
Bernhard Lehnertz
Rodrigo Mendoza-Sanchez
Réjean Ruel
Thierry Bertomeu
Jasmin Coulombe-Huntington
Geneviève Boucher
Nandita Noronha
Caroline Pabst
Mike Tyers
Patrick Gendron … (voir 5 de plus)
Sébastien Lemieux
Frederic Barabe
Anne Marinier
Josée Hébert
Guy Sauvageau
Key Points Inhibition of RAB protein function mediates the anti–acute myeloid leukemia activity of statins. Statin sensitivity is associat… (voir plus)ed with enhanced vesicle-mediated traffic.
2021-11-03
Blood Advances (publié)
doi.org