A5084362699- Cell death mechanisms and regulation
- RNA Interference and Gene Delivery
- Mitochondrial Function and Pathology
- Lipid Membrane Structure and Behavior
- ATP Synthase and ATPases Research
- Cancer, Stress, Anesthesia, and Immune Response
- PARP inhibition in cancer therapy
- Cancer-related Molecular Pathways
- Phagocytosis and Immune Regulation
- Connective Tissue Growth Factor Research
- Force Microscopy Techniques and Applications
- Retinoids in leukemia and cellular processes
- interferon and immune responses
- Cancer Research and Treatments
- Cellular Mechanics and Interactions
- Neuroscience and Neuropharmacology Research
- Tissue Engineering and Regenerative Medicine
- Metabolomics and Mass Spectrometry Studies
Sunnybrook Health Science Centre
2017-2023
University of Toronto
2016-2023
Sunnybrook Research Institute
2019-2023
Queen's University
2014
Tumor initiation, progression and resistance to chemotherapy rely on cancer cells bypassing programmed cell death by apoptosis. We report that unlike other pro-apoptotic proteins, Bim contains two distinct binding sites for the anti-apoptotic proteins Bcl-XL Bcl-2. These include BH3 sequence shared with an unexpected located near carboxyl-terminus (residues 181-192). Using automated Fluorescence Lifetime Imaging Microscopy - Resonance Energy Transfer (FLIM-FRET) we show interfaces enable...
Abstract Bax proteins form pores in the mitochondrial outer membrane to initiate apoptosis. This might involve their embedding cytosolic leaflet of lipid bilayer, thus generating tension induce a pore with radially arranged lipids forming wall. Alternatively, comprise part However, there is no unambiguous structural evidence for either hypothesis. Using NMR, we determined high‐resolution structure core region, revealing dimer nonpolar surface covering bilayer edge and polar exposed water....
Anti-apoptotic proteins such as BCL-XL promote cell survival by sequestering pro-apoptotic BCL-2 family members, an activity that frequently contributes to tumorigenesis. Thus, the development of small-molecule inhibitors for anti-apoptotic proteins, termed BH3-mimetics, is revolutionizing how we treat cancer. BH3 mimetics kill cells displacing sequestered initiate tumor-cell death. Recent evidence has demonstrated in live BH3-only PUMA and BIM resist displacement while others like tBID do...
Abstract Invadopodia are extracellular matrix (ECM)-degrading structures that promote tissue invasion and metastasis of tumor cells. A family adaptor proteins with F-BAR SH3 domains, including FBP17 Toca-1, have been identified as key scaffolds for recruiting actin regulatory (eg. Cdc42, formins, N-WASP, dynamin) to formation invadopodia in bladder breast cancers, respectively. In this study, we investigated the potential role cancer models. We observed expression normal epithelial cells...
Abstract Anti-apoptotic proteins such as BCL-X L promote cell survival by sequestering pro-apoptotic BCL-2 family members, an activity that frequently contributes to tumorigenesis. Thus, the development of small-molecule inhibitors for anti-apoptotic proteins, termed BH3-mimetics, is revolutionizing how we treat cancer. BH3 mimetics kill cells displacing sequestered initiate tumor-cell death. Recent evidence has demonstrated in live BH3-only PUMA and BIM resist displacement while others like...