Office: SCIE 3463
Laboratory: SCIE 3405-6
My research seeks to uncover the mechanisms controlling the survival of cells under stress. Cellular stress can trigger a process of self-destruction known as apoptosis. Stress-induced apoptosis is initiated by the release of cytochrome c from the mitochondrial intermembrane space into the cytoplasm leading to the activation of a specific family of proteases known as caspases. Once activated the caspases dismantle the cell, converting it to a form that can be recognized and removed by phagocytic cells. Cells have devised numerous strategies to prevent unintentional activation of the apoptotic death pathway. These safeguards allow cells to cope with minor fluctuations in their environment. One of these adaptive responses to stress is the coordinate upregulation of a family of proteins known as the heat shock proteins (hsp). These proteins play essential roles in protein folding and are commonly referred to as molecular chaperones. Although it was realized soon after their discovery that these proteins have general cytoprotective properties it was only recently that they were shown to block stress-induced apoptosis. The specific aims of my research are to determine how heat shock triggers the apoptotic program and how this process is inhibited by the heat shock protein hsp70.
Mosser DD, Caron AW, Bourget L, Meriin, AB, Sherman MY, Morimoto RI, Massie B. (2000) The chaperone function of HSP70 is required for protection against stress-induced apoptosis. Molecular and Cellular Biology, 20:7146-7159.
Gabai VL, Meriin AB, Yaglom JA, Wei JY, Mosser DD, Sherman, MY (2000) Suppression of stress kinase JNK is involved in HSP72-mediated protection of myogenic cells from transient energy deprivation: Hsp72 alleviates the stress-induced inhibition of JNK dephosphorylation. Journal of Biological Chemistry, 275:38088-38094.
Gabai VL, Yaglom JA, Volloch V, Meriin AB, Force T, Koutroumanis M, Massie B, Mosser DD, Sherman MY (2000) Hsp72-mediated suppression of c-jun N-terminal kinase is implicated in development of tolerance to caspase-independent cell death. Molecular and Cellular Biology, 20:6826-6836.
Beere HM, Wolf BB, Cain K, Mosser DD, Mahboubi A, Kuwana T, Tailor P, Morimoto RI, Cohen G, Green DR. (2000) Heat shock protein 70 (HSP70) inhibits apoptosis by preventing recruitment of procaspse-9 to the Apaf-1 apoptosome. Nature Cell Biology, 2:469-475.
Caron AW, Massie B, Mosser DD (2000) Use of a micromanipulator for high-efficiency cloning of cells labeled with fluorescent proteins. Methods in Cell Science, 22(2-3):137-45.
Yaglom JA, Gabai VL, Meriin AB, Mosser DD, Sherman MY. (1999) The function of HSP72 in suppression of c-Jun N-terminal kinase activation can be dissociated from its role in prevention of protein damage. Journal of Biological Chemistry 274:20223.
Meriin AB, Yaglom JA, Gabai VL, Mosser DD, Zon L, Sherman MY. (1999) Protein-damaging stresses activate c-Jun N-terminal kinase via inhibition of its dephosphorylation: A novel pathway controlled by hsp72. Molecular and Cellular Biology 19:2547-2555.
Mercille, S, Jolicoeur, P, Gervais, C, Paquette D, Mosser, DD, and Massie, B (1999) Dose-dependent reduction of apoptosis in nutrient-limited cultures of NS/0 myeloma cells transfected with the E1B-19K adenoviral gene. Biotechnology and Bioengineering. 63:516-528.
Massie B, Mosser DD, Koutroumanis M, Vitté-Mony I, Lamoureux L, Couture F, Paquet L, Guilbault C, Dionne J, Chahla D, Jolicoeur P, Langelier Y. (1998) New adenovirus vectors for protein production and gene transfer. Cytotechnology 28:1-12.
Volloch V, Mosser DD, Massie B, Sherman MY. (1998) Reduced thermotolerance in aged cells results from a deficient hsp72-mediated control of JNK signaling pathway. Cell Stress and Chaperones. 3:265-271.
Shi, Y, Mosser, DD, Morimoto, RI (1998) Molecular chaperones as HSF1-specific transcriptional repressors. Genes & Development 12:654-666.
Massie B, Couture F, Lamoureux L, Mosser DD, Guilbault C, Jolicoeur P, Bélanger F, Langelier Y. (1998) Inducible overexpression of a toxic protein with adenovirus vector using a tetracycline-regulatable expression cassette. Journal of Virology 72:2289-2296.
Mosser DD, Caron AW, Bourget L, Denis-Larose C, Massie B (1997) Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Molecular and Cellular Biology 17: 5317-5327.
Gabai VL, Meriin A, Mosser DD, Caron AW, Rits S, Shifrin VI, Sherman MY. (1997) Hsp70 prevents activation of stress-activated kinases: A novel pathway of cellular thermotolerance. Journal of Biological Chemistry 272:18033-18037.
Mosser DD, Caron AW, Bourget L, Jolicoeur P, Massie B (1997) Use of a dicistronic expression cassette encoding the green fluorescent protein for the screening and selection of cells expressing inducible gene products. BioTechniques 22:150-161.
Lachapelle, Guillaume (Ph.D.)
Livingstone, Aaron (M.Sc.)
Radicioni, Stefanie (M.Sc.)
Simard, Jodie (M.Sc.)
Stankiewicz, Adam (Ph.D.)