Dr. Sharon M. Gorski, PhD
Senior Scientist, Michael Smith Genome Sciences Centre, BC Cancer Agency
Associate Professor, Department of Molecular Biology and Biochemistry, Simon Fraser University
Affiliate Associate Professor, Department of Medical Genetics, University of British Columbia
B.Sc., Biology (honours), Science Co-operative Education Program, Certificate Program in Liberal Arts, Simon Fraser University
M.Sc., Genetics, Department of Medical Genetics, University of British Columbia
Ph.D., Developmental Biology, Division of Biology and Biomedical Sciences, Washington University School of Medicine, St. Louis, USA
The study of autophagy (= “self-eating”) has generated tremendous attention due to the recognition that autophagy is involved in multiple developmental processes and various human diseases including cancer. Autophagy is a catabolic cellular process that provides nutrients and energy through lysosomal degradation of cytoplasmic components engulfed in double membrane-bound vesicles known as autophagosomes. Autophagy occurs at basal rates in virtually all eukaryotic cells to fulfill homeostatic functions such as the recycling of long-lived proteins and damaged organelles. Under cellular stress conditions, autophagy is upregulated as an adaptive survival response. Cancer cells may exploit elevated autophagy to survive low nutrient conditions, fuel proliferation, and escape the effects of chemotherapy and radiation treatments. Consequently, autophagy is under investigation as a novel target for anticancer therapy. However, our understanding of the mechanisms by which cells utilize the autophagy pathway to promote both normal development and cancer progression is in its infancy. To help elucidate these mechanisms, the overall goals of my research program are to identify and characterize regulators of autophagy; investigate the roles of autophagy during normal development; and evaluate the therapeutic potential of autophagy modulation for cancer treatment.
GFP-LC3 autophagosomes in breast cancer cells.
Current research projects include the following areas of investigation:
- Autophagy and apoptosis crosstalk in Drosophila and mammalian model systems
- Autophagy as a therapeutic target in breast cancer
- Autophagy-related mutations in human cancers
- Screening for candidate inhibitors of autophagy proteins
Chittaranjan S, Chan S, Yang C, Yang K, Chen V, Moradian A, Firme M, Song J, Go N, Blough M, Chan JA, Cairncross G, Gorski SM, Morin GB, Yip S, Marra MA. Mutations in CIC and IDH1 cooperatively regulate 2-hydroxyglutarate levels and cell clonogenicity. Oncotarget. 2014 Sep 15;5(17):7960-79.
DeVorkin L, Gorski SM. A mitochondrial-associated link between an effector caspase and autophagic flux. Autophagy. 2014 Oct 1;10(10):1866-1867.
Chittaranjan S, Bortnik S, Dragowska V, Xu J, Abeysundra N, Leung A, Erro Go N, DeVorkin L, Weppler S, Gelmon K, Yapp D, Bally M, Gorski SM. Autophagy inhibition augments the anticancer effects of epirubicin treatment in anthracycline-sensitive and resistant triple negative breast cancer. Clinical Cancer Research. 2014 Jun 15;20(12):3159-73.
Rothe K, Lin H, Lin KB, Leung A, Wang HM, Malekesmaeili M, Brinkman RR, Forrest DL, Gorski SM, Jiang X. Identification of the core autophagy protein ATG4B as a potential biomarker and therapeutic target in CML stem/progenitor cells. Blood. 2014 Jun 5;123(23):3622-34.
DeVorkin L, Go NE, Hou YC, Moradian A, Morin GB, Gorski SM. The Drosophila effector caspase Dcp-1 regulates mitochondrial dynamics and autophagic flux via SesB. Journal of Cell Biology. 2014 May 26;205(4):477-492.
Jardon MA, Rothe K, Bortnik S, Vezenkov L, Jiang X, Young RN, Lum JJ, Gorski SM. Autophagy: From structure to metabolism to therapeutic regulation. Autophagy. 2013 Dec;9(12):2180-2.
Dragowska WH, Weppler SA, Wang JC, Wong LY, Kapanen AI, Rawji JS, Warburton C, Qadir MA, Donohue E, Roberge M, Gorski SM, Gelmon KA, Bally MB. Induction of autophagy is an early response to gefitinib and a potential therapeutic target in breast cancer. PLoS One. 2013 Oct 11;8(10):e76503.
Lebovitz CB, Bortnik SB and Gorski SM. Here there be dragons: Charting autophagy-related alterations in human tumors. Clinical Cancer Research, 2012 Mar 1;18(5): 1214-26.
Jardon MA, Sattha B, Braasch K, Leung AO, Côté HC, Butler M, Gorski SM, Piret JM. Inhibition of glutamine-dependent autophagy increases t-PA production in CHO Cell fed-batch processes. Biotechnol Bioeng. 2012 May;109(5):1228-38.
Chittaranjan S, McConechy M, Hou YC, Freeman JD, DeVorkin L and Gorski SM. Steroid hormone control of cell death and cell survival: molecular insights using RNAi. Plos Genetics. 2009, 5(2) e/000379.
Hannigan AM, Gorski SM. Macroautophagy: The key ingredient to a healthy diet? Autophagy. 2009 Feb 3;5(2): 140-51.
Hou YC, Hannigan AM, Gorski SM. An executioner caspase regulates autophagy. Autophagy. 2009, May;5(4):530-3.
Hou YC, Chittaranjan S, Gonzalez S, McCall K and Gorski SM. Effector caspase Dcp-1 and IAP protein Bruce regulate starvation-induced autophagy during Drosophila melanogaster oogenesis. The Journal of Cell Biology. 2008, Sept. 22;182(6):1127-39.
Qadir M, Kwok B, Dragowska WH, To KH, Le D, Bally MB, and Gorski SM. Macroautophagy inhibition sensitizes tamoxifen-resistant breast cancer cells and enhances mitochondrial depolarization. Breast Cancer Research and Treatment. 2008 Dec;112(3):389-403.
Recent Book Chapters
Chittaranjan S, Bortnik SB and Gorski SM. Monitoring autophagic flux using lysosomal inhibitors and endogenous LC3B western blotting. Protocol for book chapter entitled "Autophagy detection techniques in primary mammalian cells." by AK Simon; in “Cell Death and Autophagy Techniques.” Editors Johnstone R and Silke J, Cold Spring Harbor Laboratory Press. 2015.
DeVorkin L, Choutka C, Gorski SM. "The interplay between autophagy and apoptosis" Chapter XXIV in Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, and Infection, Volume 3. Editor E. Hayat, Elsevier Publishing. 2014.
Phan L and Gorski SM. "Tamoxifen and Autophagy: to cease and resist" Chapter III in Tamoxifen Concepts and Cancer: New Paradigms, Nova Science Publishers, Inc. 2013.
Armstrong LJ and Gorski SM. "Breast Cancer and Autophagy" Chapter II in Breast Cancer: Causes, Diagnosis and Treatment, Nova Science Publishers, Inc. 2010.
Sharon Gorski's Complete Publications List including selected links to full text articles.