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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EPH receptor tyrosine kinases phosphorylate the PAR-3 scaffold protein to modulate downstream signaling networksJournal Article
Cell Rep, 40 (1), 2022.
CDK1-Mediated Phosphorylation of BAG3 Promotes Mitotic Cell Shape Remodeling and the Molecular Assembly of Mitotic p62 BodiesJournal Article
Cells, 10 (10), 2021.
Metformin rescues muscle function in BAG3 myofibrillar myopathy modelsJournal Article
Autophagy, 17 (9), 2021.
Chaperone-Assisted Mitotic Actin Remodeling by BAG3 and HSPB8 Involves the Deacetylase HDAC6 and Its Substrate CortactinJournal Article
Int J Mol Sci, 22 (1), 2020.
The adenoviral protein E4orf4: a probing tool to decipher mechanical stress-induced nuclear envelope remodeling in tumor cellsJournal Article
Cell Cycle, 19 (22), 2020.
Adenoviral protein E4orf4 interacts with the polarity protein Par3 to induce nuclear rupture and tumor cell deathJournal Article
J Cell Biol, 219 (4), 2020.
BAG3 Mice as a Model of BAG3 Myofibrillar MyopathyJournal Article
Am J Pathol, 190 (3), 2020.
HSPB8 and BAG3 cooperate to promote spatial sequestration of ubiquitinated proteins and coordinate the cellular adaptive response to proteasome insufficiencyJournal Article
FASEB J, 32 (7), 2018.
Fine-tuning of actin dynamics by the HSPB8-BAG3 chaperone complex facilitates cytokinesis and contributes to its impact on cell divisionJournal Article
Cell Stress Chaperones, 22 (4), 2017.
Keratin 8/18 regulation of insulin receptor signaling and trafficking in hepatocytes through a concerted phosphoinositide-dependent Akt and Rab5 modulationJournal Article
FASEB J, 31 (8), 2017.
- Regulation of nuclear dynamics by tyrosine kinase signaling, from 2022-04-01 to 2027-03-31
- TBC1D9: therapeutic target of the aggressiveness of triple negative breast cancer, from 2023-03-01 to 2024-02-29
Recently finished projects
- Bourse Concert pour la vie , from 2020-11-13 to 2021-11-12
- Deciphering mechanical stress-induced nuclear envelope remodeling in tumor cells, from 2020-09-01 to 2022-08-31
- Tyrosine kinase signaling in Nuclear Morphodynamics., from 2016-04-01 to 2022-03-31