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Dr. George Zogopoulos is one of Canada’s leading hepato-pancreato-biliary surgeons and an expert in pancreatic cancer. He established the Quebec Pancreas Cancer Study, Quebec’s first prospective clinical research registry and biobank for pancreatic cancer. He is one of the lead investigators of EPPIC (Enhanced Pancreatic Cancer Profiling for Individualized Care), a Translational Research Program funded by the Terry Fox Research Institute that unites leading pancreatic cancer researchers from across Canada.

He is also an important contributor to other national and international pancreatic cancer research teams and consortia including Pancreatic Cancer Genetic Epidemiology Consortium (PACGENE), The Pancreatic Canadian Oncology Network (PancOne) and the Pancreatic Cancer Early Detection Consortium (PRECEDE), and he plays a leading role in the Quebec Cancer Consortium (QCC) and Marathon of Hope Cancer Centres Network (MoHCCN).

Dr. Zogopoulos’ lab pursues a program of translational research on pancreatic cancer that applies genomics to both patient samples and tumour models established directly from patient tumours. His studies are identifying the genetic changes that confer susceptibility to pancreatic cancer and drive its formation and progression, as well as revealing ways to match pancreatic cancer subtypes with the best treatment options.

Dr. Zogopoulos is also renowned for his skill and innovation in pancreatic surgical oncology and transplantation surgery, and he received the Michal & Renata Hornstein Career Award for Surgical Excellence in 2021.

Publication highlights:

• A Preclinical Trial and Molecularly Annotated Patient Cohort Identify Predictive Biomarkers in Homologous Recombination-deficient Pancreatic Cancer. Wang Y, et al. Clin Cancer Res. 2020 Oct 15;26(20):5462-5476. doi: 10.1158/1078-0432.CCR-20-1439. PMID: 32816949
• A region-based gene association study combined with a leave-one-out sensitivity analysis identifies SMG1 as a pancreatic cancer susceptibility gene. Wong C, et al. PLoS Genet. 2019 Aug 30;15(8):e1008344. doi: 10.1371/journal.pgen.1008344. PMID: 31469826
• Reflex Testing for Germline BRCA1, BRCA2, PALB2, and ATM Mutations in Pancreatic Cancer: Mutation Prevalence and Clinical Outcomes From Two Canadian Research Registries. Smith AL, et al. JCO Precis Oncol. 2018 Nov;2:1-16. doi: 10.1200/PO.17.00098. PMID: 35135108

The GCI has made important contributions to understanding how changes in metabolism contribute to pancreatic cancer through collaborative studies which revealed new therapeutic targets in pancreatic cancer and uncovered fundamental mechanisms of pancreatic inflammation, which is an important predisposing factor to cancer and other pancreatic diseases.

These studies have been spearheaded at the GCI by the Metabolomics Innovation Resource (MIR), our ground-breaking technology platform for comprehensive metabolic profiling, under the leadership of Prof. Peter Siegel and Platform Manager Daina Avizonis, PhD. The MIR is supported by a Terry Fox New Frontiers Program Project Grant on "Targeting the Metabolic Vulnerabilities of Cancer" led by Prof. Peter Siegel, with the support of the Terry Fox Research Institute and the Quebec Breast Cancer Foundation. It has also been supported by major investments from the Canada Foundation for Innovation and the Dr. John R. and Mrs. Clara M. Fraser Trust.

Publication highlights, in collaboration with Prof. Christine Chio (Columbia University), Prof. Jerry Pelletier and Prof. Michael Pollak:

• eIF4A supports an oncogenic translation program in pancreatic ductal adenocarcinoma. Chan et al. Nat Commun. 2019 Nov 13;10(1):5151. doi: 10.1038/s41467-019-13086-5. PMID: 31723131 from ).
• Methionine oxidation activates pyruvate kinase M2 to promote pancreatic cancer metastasis. He et al. Mol Cell. 2022 Aug 18;82(16):3045-3060.e11. doi: 10.1016/j.molcel.2022.06.005. Epub 2022 Jun 24. PMID: 35752173

Publication highlights, in collaboration with Prof. Nika Danial (Harvard University) and Daina Avizonis:

• Glucose-dependent partitioning of arginine to the urea cycle protects β-cells from inflammation. Fu et al. Nat Metab. 2020 May;2(5):432-446. doi: 10.1038/s42255-020-0199-4. Epub 2020 May 11. PMID: 32694660
• Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in pancreatic islets. Fu et al. Cell Rep. 2021 Nov 23;37(8):110037. doi: 10.1016/j.celrep.2021.110037. PMID: 34818536

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Prof. Nahum Sonenberg has contributed his world-renowned expertise on mRNA translation to several important studies of pancreatic cancer biology. These have uncovered mechanisms by which mRNA translation programs involved in cellular responses to stress contribute to pancreatic cancer development and progression.

Publication highlights:

• ATF4-mediated induction of 4E-BP1 contributes to pancreatic beta cell survival under endoplasmic reticulum stress. Yamaguchi et al. Cell Metab. 2008 Mar;7(3):269-76. doi: 10.1016/j.cmet.2008.01.008. PMID: 18316032 (collaboration led by Hisamitsu Ishihara and Yoshitomo Oka, Sendai University, Japan)
• NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer. Chio et al. Cell. 2016 Aug 11;166(4):963-976. doi: 10.1016/j.cell.2016.06.056. PMID: 27477511 (collaboration with the lab of Prof. David Tuveson, Cold Spring Harbor Laboratory)

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Prof. Michel Tremblay, working with Prof. Jerry Pelletier, Dr. George Zogopoulos, and colleagues, discovered that tyrosine phosphatases, key proteins that control cellular signaling pathways, are important in regulating the function of dendritic cells, a key immune cell type involved in anti-tumour responses. They showed that drugs blocking the activity of these enzymes, known as PTP1B and TC-PTP, can boost the function of dendritic cells isolated from pancreatic cancer patients, which are normally defective. These findings suggest that targeting PTP1B and TC-PTP can be an important part of an immunotherapy strategy for pancreatic and other cancers. This is currently being pursued by Kanyr Pharma, a company co-founded by Prof. Tremblay.

• Downregulation of PTP1B and TC-PTP phosphatases potentiate dendritic cell-based immunotherapy through IL-12/IFNγ signaling. Penafuerte C, et al. Oncoimmunology. 2017 Apr 28;6(6):e1321185. doi: 10.1080/2162402X.2017.1321185. PMID: 28680757