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.
- Simard JP, Reynolds DN, Kraguljac AP, Smith GST, Mosser DD (2011) Hsp70 overexpression inhibits cofilin phosphorylation and promotes lymphocyte migration in heat-stressed cells. Journal of Cell Science 124:2367-2374.
- Stankiewicz AR, Livingstone AM, Mosser DD. (2009) Regulation of heat-induced apoptosis by Mcl-1 degradation and its inhibition by Hsp70. Cell Death & Differentiation 16:38-647.
- Lachapelle G , Radicioni SM , Stankiewicz AR , Mosser DD (2007) Acute acidification or amiloride treatment suppresses the ability of Hsp70 to inhibit heat-induced apoptosis. Apoptosis 12:1479-1488.
- Stankiewicz AR, Lachapelle G, Foo CP, Radicioni SM, Mosser DD. (2005) Hsp70 inhibits heat-induced apoptosis upstream of mitochondria by preventing Bax translocation Journal of Biological Chemistry 280(46):38729-39.
- Mosser DD, Ho S, JR Glover (2004) Saccharomyces cerevisiae Hsp104 enhances the chaperone capacity of human cells and inhibits heat stress-induced proapoptotic signaling. Biochemistry 43:8107-15.
- Mosser DD, Morimoto RI (2004) Molecular chaperones and the stress of oncogenesis. Oncogene 23:2907-2918.
Rabih Roufayel (Ph.D)
Rebecca Rumney (M.Sc.)