Ing Swie Goping
Ph.D, McGill University
Adjunct Professor, Oncology
Apoptosis is a programmed cell death process that is vital for proper development and tissue homeostasis. Notably, impaired apoptosis contributes to the development of cancer and is a major barrier to effective treatment. Two ongoing projects in the lab address the issues of chemotherapeutic resistance and apoptosis in breast cancer cells:
1. Identifying predictive markers for chemotherapeutic resistance. Breast cancer is the most frequently diagnosed cancer in Canadian women with 23,400 new cases reported in 2011. Chemotherapy that includes the microtubule-inhibiting agents taxanes, is given to thousands of Canadian women every year. Acquired or de-novo resistance, however, is a major clinical problem that manifests in 50-70% of those treated for metastatic disease. Lack of predictive markers prevents personalized treatment for taxane chemotherapy. We identified that the Bcl-2 family member Bad is a strong, independent prognostic indicator for disease free- and overall survival of breast cancer patients after adjuvant taxane chemotherapy. As well, we identified that another cellular programme known as autophagy, enhanced cell death in response to taxanes and that gene expression of a subset of autophagy regulators correlated with beneficial clinical outcome. Thus, in collaboration with clinical collaborators, we are pursuing the utility of marker expression as predictive indicators for chemoresistance to taxane therapy and are investigating the basic signaling pathways in their activity.
2. Elucidate the role of Bad in breast cancer. We have discovered that the protein Bad has unexpected functions in breast cancer cells. Using a combination of biochemistry, genetics and cell biology techniques, we are investigating the molecular mechanisms of Bad activity. We identify functionally relevant regulatory proteins, use molecular biology approaches to design variants of these proteins to assess their activities, and cell imaging techniques to uncover the roles of these proteins in cell signaling pathways. Our discoveries lead to hypotheses that are then tested on clinical samples. By more fully understanding these processes we hope to uncover novel insights that can be explored for the treatment of cancers or other proliferative diseases.
Apoptosis. Colloquium series on Building Blocks of the Cell: Cell Structure and Function.
Yang N, Goping IS.
Morgan and Claypool Life Sciences. Series Editor, Ivan Robert Nabi (2013) Vol. 1, No. 3 , Pages 1-101.
The chemotherapeutic agent paclitaxel inhibits autophagy through two distinct mechanisms that regulate apoptosis.
Veldhoen RA, Banman S, Hemmerling D, Odsen R, Simmen T, Simmonds A, Underhill DA, Goping IS.
Oncogene (2012) 7: 736-46.
The Rubella virus capsid is an anti-apoptotic protein that attenuates the pore-forming ability of Bax.
Ilkow CS, Goping IS, Hobman TC.
PLOS Pathogen (2011) 7: e1001291.
The BH3-only protein Bad confers breast cancer taxane sensitivity through a non-apoptotic mechanism.
Craik AC, Veldhoen RA, Czernick M, Buckland TW, Kyselytzia K, Ghosh S, Lai R, Damaraju S, Underhill DA, Mackey JR, Goping IS.
Oncogene (2010) 29: 5381.
Bim is reversibly phosphorylated but plays a limited role in paclitaxel cytotoxicity of breast cancer cell lines.
Czernick M, Rieger A, Goping IS.
Biochem. Biophys. Res. Commun. (2009)379: 145-50.
Autotaxin protects MCF-7 breast cancer and MDA-MB-435 melanoma cells against Taxol-induced apoptosis.
Samadi N, Gaetano C, Goping IS, Brindley DN.
Oncogene (2009)28: 1028-39.