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Pharmacology Seminar – Dr. Spencer Gibson
Posted on: December 13, 2011
PDF Date: Friday, December 16, 2011
Time: 9:00 am
Location: Samuel Cohen Auditorium **
** videolink to Bannatyne Campus (Pharmacology Library, Chown Bldg.)
Topic: How to selectively target cancer cells to die?
Spencer B. Gibson,
Acting Director,
Manitoba Institute of Cell Biology Research
CancerCare Manitoba
Professor and Manitoba Chair,
Departments of Biochemistry and Medical Genetics and Immunology, University of Manitoba
Dr. Spencer B. Gibson is a Professor in the Department of Biochemistry and Medical Genetics at the University of Manitoba and is a Senior Investigator at the Manitoba Institute of Cell Biology since 1999. In 2008, the Manitoba Health Research Council awarded Dr. Gibson a Manitoba Research Chair to support his research efforts. At the Manitoba Institute of Cell Biology, Dr. Gibson is Director of Translational Research where he contributed to the creation of the expansion of the Manitoba Tumor Bank and initiated new translational research projects. He is also appointed as Provincial Director of Research, CancerCare Manitoba, to provide leadership for cancer research with the province of Manitoba. Dr. Gibson attended the University of Toronto where he gained his Ph.D. in the Department of Laboratory Medicine and Pathobiology. During his Ph.D. studies, he traveled to M.D. Anderson Cancer Center in Houston, Texas as a pre-doctoral fellow where he completed his Ph.D. studies. Dr. Gibson was a post-doctoral fellow at the National Jewish Medical and Research Center in Denver, Colorado
RESEARCH PROGRAM: Discovering Signal Transduction Pathways Regulating Cell Death.
In maintaining integrity and homeostasis of multicellular organisms, the balance between cell death and survival is fundamentally important. When this balance is altered diseases occur such as cancer. One protein important in regulation of cell death is the Bcl-2 BH-3 only member BNIP3. BNIP3 expression is induced under low oxygen (hypoxia) conditions and is over expressed in solid tumors in hypoxic regions. When BNIP3 is over expressed in cancer cells it induces cell death mediated by mitochondrial dysfunction. This cell death instead of being apoptotic is autophagic (a new form of programmed cell death). This paradox of BNIP3 killing cancer cells and being over expressed in live cells within tumors is a focus of our research. To date three explanations could account of these differences. The first difference is growth factors block BNIP3 cell death function and tumors have deregulated growth factor signaling leading to cell survival (see below). Secondly, BNIP3 is also localized in the nucleus of tumor cells prevent its interaction with the mitochondria blocking its cell death function. Finally, the BNIP3 gene is mutated to an inactive protein. This protein acts in a dominant negative fashion blocking hypoxia induced cell death. The importance of these mechanisms for cancer progression and treatment is under active investigation.
Cell survival is as important as cell death. The epidermal growth factor receptor (EGFR) is expressed at high levels in several cancers such as breast cancer. We discovered that pretreatment of breast cancer cell lines with epidermal growth factor (EGF) effectively blocked drug and death receptor induced apoptosis. This protection from apoptosis is mediated by a serine threonine kinase called AKT through up-regulation of the Bcl-2 anti-apoptotic family member Mcl-1. Besides breast cancer, we have found that a lipid, lysophosphatic acid (LPA) blocks apoptosis in chronic lymphocytic leukemia (CLL) cells using a similar mechanism. We are currently investigating the regulatory elements controlling Mcl-1 expression.
Molecular-based therapies could alter the balance between cell death and survival towards killing cancer cells. Tumor necrosis factor related apoptosis-inducing ligand (TRAIL) selectively kills cancer cells while normal cells are resistant to TRAIL-induced apoptosis. In collaboration with Dr. James Johnston, we are investigating the potential of TRAIL as a therapy for chronic lymphocytic leukemia (CLL) alone or in combination with chemotherapy.
For more information, please contact Dr. Ben Albensi, Seminar Coordinator at balbensi@sbrc.ca or call 204.235.3939.