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Dr. Sharon M. Gorski, PhD

Distinguished Scientist, Canada's Michael Smith Genome Sciences Centre, BC Cancer

Phone 604-675-8113
Fax 604-675-8178


Professor, Department of Molecular Biology and Biochemistry, Simon Fraser University 
Affiliate Professor, Department of Medical Genetics, University of British Columbia

Professional Profile

Dr. Gorski completed a PhD in Biology and Biomedical Sciences at Washington University School of Medicine, St. Louis, MO in 1999. She then conducted postdoctoral studies at the British Columbia Cancer Agency where she utilized genomics approaches to study cell death and cell survival pathways. Dr. Gorski is currently a Distinguished Scientist at Canada’s Michael Smith Genome Sciences Centre at BC Cancer and a Professor in the Department of Molecular Biology and Biochemistry at Simon Fraser University. Her research program includes analyses of cell stress responses and cancer-related signaling pathways, with a focus on breast and pancreatic cancers.

Research Projects

Autophagy is an intracellular recycling process that promotes homeostasis, stress adaptation and cell survival. The autophagy process 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. In this way, autophagy acts to safeguard genome integrity and suppress tumorigenesis. 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 other treatments.

Consequently, autophagy is under investigation as a target for anticancer therapy in preclinical studies and clinical trials. However, our understanding of the mechanisms by which cells utilize the autophagy pathway to promote both normal development and cancer progression is limited.

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 cancer progression, and evaluate the therapeutic potential of autophagy modulation for cancer treatment.

Molecular dissection of Pancreatic Neuroendocrine Tumours

Pancreatic neuroendocrine tumours (PNETs) are an under-studied type of tumour that are rare but clinically challenging due to late detection, variable progression and frequent metastasis. The molecular basis of PNETs is not well understood and there are no prognostic markers to aid PNET clinical management. The overall aim of this study is to provide a comprehensive molecular characterization of PNETs to better understand disease progression and heterogeneity, and to devise clinically relevant subclasses. By integrating RNA-sequencing based transcriptome profiling and an innovative new technology for proteomic profiling of tumour specimens, this study will explore the proteogenomic landscape of PNETs.  In addition to identifying disease classifiers, this study will lay the groundwork for further investigations of candidate biomarkers, potential driver mutations and therapeutic targets.

Autophagy and its interplay with cellular stress response pathways.

Caspases are cysteine-aspartic acid proteases that were traditionally associated with roles in apoptosis and inflammation. Dr. Gorski’s lab identified a role for the Drosophila effector caspase Dcp-1 in the positive regulation of stress-induced autophagy and current efforts are focused on elucidating the regulation and molecular mechanisms of caspase-mediated autophagy, as well as its evolutionary conservation in mammalian cells. 

Another response to cellular stress is the release of extracellular vesicles. Emerging evidence from normal and disease contexts is beginning to reveal a coordinated stress response between extracellular vesicle release and autophagy to help sustain homeostasis. The group is investigating the functional relationships and coordinated regulation between the autophagy pathway and extracellular vesicles.

Roles of macroautophagy in Drosophila development

The goal of Dr. Gorski’s laboratory in carrying out this research is to increase our understanding of the regulation and functions of autophagy in the context of a whole organism. To achieve this goal, they are using the fruit fly, Drosophila melanogaster, a model organism, which has evolutionarily conserved autophagy-related (Atg) genes and pathways. They have developed reporter tools to help study autophagy in fly cell lines and in various fly tissues in vivo. They are now combining these tools with the powerful genetic analyses possible in this model system to study the roles of autophagy during normal development and to identify and characterize new regulators and effectors of Atg proteins and the autophagy pathway.

New strategies to target Pancreatic Ductal Adenocarcinoma (PDAC)

Recent studies show that PDAC tumours are dependent on the cell survival and stress adaptation process called autophagy. Studies using pancreatic cancer cells and animal models have shown that inhibiting autophagy can slow tumour growth and enhance the effects of anti-cancer treatments. The overall objective of this study is to investigate the biological roles and therapeutic target potential of all four ATG4 family proteins in pancreatic cancer. They will examine how ATG4 inhibition affects proteins and processes within the tumour and in surrounding cells. Together, these studies will provide new knowledge on the biological roles and therapeutic potential of ATG4 family proteins in pancreatic cancer and may lead to the development of an urgently needed new treatment option for patients with pancreatic cancer.

Tackling treatment resistance in HER2-positive Breast Cancer

Approximately 20% of breast cancers have amplification of the gene encoding HER2, a protein that promotes cell growth and proliferation. While there are therapies designed specifically to treat HER2-positive cancer, treatment resistance presents a substantial challenge. The Gorski laboratory recently discovered a novel association between HER2 and an autophagy-related cysteine protease called ATG4B and found that ATG4B inhibition sensitizes treatment-resistant HER2-positive breast cancer cell lines to anti-HER2 treatment. As a result, they are investigating the clinical relevance, therapeutic potential, and regulation of ATG4B in the context of HER2-positive breast cancer. Understanding how HER2 influences ATG4B could lead to the identification of new targets or combination targeting strategies. These studies have the potential to validate ATG4B as a new therapeutic target to help overcome treatment resistance in HER2-positive breast cancers.