Holder of a PhD in Cellular and Molecular Biology, Dr. Josée N. Lavoie is a regular researcher at the CHU Research Centre of Quebec-Laval University, oncology axis, and Professor in the Department of Molecular Biology, Medical Biochemistry and Pathology of the Faculty of Medicine at Laval University. She is also a regular researcher at the Centre for Cancer Research at Laval University, and Director of Graduate Programs in Cellular and Molecular Biology of the Faculty of Medicine at Laval University. Her research focuses on fundamental aspects of cell biology, including the molecular mechanisms that control cell division and morphological changes relevant to the development of malignant tumor cell properties. Her work has helped identify the role of small molecular chaperones from the heat shock protein family in cellular stress resistance and cytoskeletal remodeling, as well as highlighting non-apoptotic cell death processes in cancer cells.
Dr. Lavoie received the 2016 Award of Excellence from the Department of Molecular Biology, Medical Biochemistry and Pathology for her contributions to research, teaching and academic management. She has been commissioned, as an expert, to serve on numerous peer review committees of Graduate Studies Research and Training Programs.
Defining the mode of action of the HSPB8-BAG3 chaperone complex in cellular morphodynamics.
Cellular remodeling is essential during processes such as mitosis and cell differentiation. It is largely driven by assembly and disassembly of actin-based mechanosensitive structures that control cell tension. By promoting the sequestration, recycling or degradation of proteins, molecular chaperones appear essential to maintain the dynamics and integrity of the macromolecular structures that form these structures. More specifically, the chaperones of the small HSP family (HSPB), including the HSPB8-BAG3 complex, contribute to and are overactivated in malignant cells. The physiopathological relevance of the HSPB8-BAG3 complex has recently been discovered in humans by identifying mutations in BAG3 and HSPB8 that lead to rare diseases, including myofibrillar myopathy, which is characterized by the fragmentation of muscle actin fibers.
The results of this research will provide insights into relevant targets for the development of novel molecular therapies.
Identify the regulatory elements of nuclear morphodynamics in response to mechanical stress.
The formation of metastases involves the invasion of tumor cells through the tight spaces of the interstitial matrix. This process requires significant cellular deformation, which is limited by the nucleus. The nucleus is surrounded by a nuclear envelope comprising a rigid network of intermediate filaments, the lamina, which protects the genetic baggage and provides resistance to deformation. Recent advances suggest that remodeling of the nucleus architecture contributes to the migration under confinement in a three-dimensional environment and influences the stability of the genome. This remodeling, induced by mechanical forces, would be controlled via physical connections between a contractile perinuclear network formed by actin, myosin II and lamina. It would also involve changes in chromatin organization and gene expression.
The results of this research will make it possible to highlight the regulatory mechanisms exploited by tumor cells during the formation of metastases.
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- Jacquet, KévinPostdoctoral fellowL'Hôtel-Dieu de Québec+1 418-525-4444, extension 16942+1 email@example.com@crchudequebec.ulaval.ca
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- Rodrigue, Marc-AntoineDoctoral studentL'Hôtel-Dieu de Québec+1 418-525-4444, extension 16942+1 firstname.lastname@example.org@crchudequebec.ulaval.ca
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The adenoviral protein E4orf4: a probing tool to decipher mechanical stress-induced nuclear envelope remodeling in tumor cells.Journal Article
Cell Cycle, pp. 1-19, 2020, ISSN: 1538-4101.
Metformin rescues muscle function in BAG3 myofibrillar myopathy models.Journal Article
Autophagy, pp. 1-17, 2020, ISSN: 1554-8627.
Adenoviral protein E4orf4 interacts with the polarity protein Par3 to induce nuclear rupture and tumor cell death.Journal Article
J Cell Biol, 219 (4), 2020, ISSN: 0021-9525.
BAG3P215L/KO Mice as a Model of BAG3P209L Myofibrillar Myopathy.Journal Article
Am J Pathol, 190 (3), pp. 554-562, 2020, ISSN: 0002-9440.
HSPB8 and BAG3 cooperate to promote spatial sequestration of ubiquitinated proteins and coordinate the cellular adaptive response to proteasome insufficiency.Journal Article
FASEB J, 32 (7), pp. 3518-3535, 2018, ISSN: 0892-6638.
Fine-tuning of actin dynamics by the HSPB8-BAG3 chaperone complex facilitates cytokinesis and contributes to its impact on cell division.Journal Article
Cell Stress Chaperones, 22 (4), pp. 553-567, 2017, ISSN: 1355-8145.
Keratin 8/18 regulation of insulin receptor signaling and trafficking in hepatocytes through a concerted phosphoinositide-dependent Akt and Rab5 modulation.Journal Article
FASEB J, 31 (8), pp. 3555-3573, 2017, ISSN: 0892-6638.
Adenofection: A Method for Studying the Role of Molecular Chaperones in Cellular Morphodynamics by Depletion-Rescue Experiments.Journal Article
J Vis Exp, (115), 2016.
A Role for the Chaperone Complex BAG3-HSPB8 in Actin Dynamics, Spindle Orientation and Proper Chromosome Segregation during Mitosis.Journal Article
PLoS Genet, 11 (10), pp. e1005582, 2015, ISSN: 1553-7390.
Regulation of Actin-Based Structure Dynamics by HspB Proteins and Partners (Chapter 18)Book Chapter
RM, Tanguay; LE, Hightower (Ed.): The big book on small heat shock proteins, pp. 435-456, Cham, Springer International Publishing, 2015, ISBN: 978-3-319-16076-4 (Print) / 978-3-319-16077-1 (Online).
- Centre de recherche du CHU de Québec - Université Laval, Subvention, Centre hospitalier universitaire de Québec - Université Laval, Centres de recherche affiliés, from 2017-01-01 to 2099-12-31
- Centre de recherche sur le cancer, Subvention, Institutionnel - BDR, BDR - Centres de recherche reconnus, from 1996-05-01 to 2022-06-13
- Deciphering mechanical stress-induced nuclear envelope remodeling in tumor cells, Subvention, Société de recherche sur le cancer, Subvention de fonctionnement, from 2020-09-01 to 2022-08-31
- Financement de votre projet de recherche dans l'Axe oncologie , Subvention, Fondation du CHU de Québec, from 2020-01-31 to 2021-01-30
- Tyrosine kinase signaling in Nuclear Morphodynamics., Subvention, Conseil de recherches en sciences naturelles et génie Canada, Subventions à la découverte SD (individuelles et d'équipe), from 2016-04-01 to 2021-03-31
Recently finished projects
- Identifier les caractéristiques définissant les cellules tumorales qui favorisent le caractère envahissant, Subvention, Société de recherche sur le cancer, Subvention de fonctionnement, from 2018-09-01 to 2020-08-31