Prof. Morag Park's Legacy: Identification and characterization of the MET oncogene

During her career of over thirty years as an independent investigator, Morag Park has consistently made outstanding and vital contributions to our understanding of cancer. A trailblazer, builder and innovator who has excelled and led in every field she has entered, Prof. Park’s extraordinary insights span a wide spectrum of cancer research, from the molecular level to the complex cellular interactions within tissues that dictate the biology of human cancers.  

This remarkable trajectory began with her identification and characterization of a key oncogene, the receptor tyrosine kinase (RTK) MET, as a post-doctoral fellow.

On this foundation, Prof. Park built a research program of sustained excellence, developing elegant molecular and cell biology approaches to systematically discover key signaling proteins and pathways dictating the functional output of MET and other RTKs. Her innovative approach, which set an example followed by many others in the field, identified critical molecular mechanisms of aberrant RTK activation that drive many prevalent cancers. These discoveries have significantly increased our understanding of many crucial processes underlying cancer development, including cell growth and proliferation, survival, motility and invasion and key cell fate decisions, such as epithelial-to-mesenchymal transition.  

Among Prof. Park’s most influential discoveries are mechanisms that activate MET following gene fusion events or through loss of a regulatory signal that leads to altered subcellular localization and increased stability of MET. These are now accepted as paradigms for activation of MET and other RTKs in human tumours.  

Throughout this impressive and growing body of work, Prof. Park has created unique and powerful reagents and tools that she has shared freely, greatly enabling the research of the entire community. Her discoveries have fostered an ongoing effort to design therapies targeting MET, several of which are now clinically approved and poised to alleviate the suffering of patients afflicted by some of the most aggressive cancers. 

While these foundational molecular and cell biology studies were transformative for the field, Prof. Park has also progressively built world-leading translational research programs, including innovative pre-clinical models and comprehensive patient sample and data repositories, particularly for breast cancer. In 1999, Prof. Park led the creation of Quebec’s first breast cancer tumour bank as well as the Breast Cancer Functional Genomics Group (BCFGG), based at McGill and involving surgeons, oncologists, pathologists, informaticians and basic and translational researchers. The BCFGG continues to house the largest and most mature clinical/biological breast cancer biobank in Quebec and one of the most significant in the country, with over 4000 breast cancer and matched normal tissue samples and an interactive data bank of associated patient information and outcomes.  

Since 2000, Prof. Park has been instrumental as Co-Principal Investigator of a Quebec-wide cancer biobanking network of clinicians and researchers. More recently, she has built “living biobanks” of live cells and tissues harvested directly from breast, stomach/esophagus, and lung cancer patients, using them to create cutting edge, patient-derived models including xenografts, organoids and 3D engineered tissues. These ongoing studies are developing a new understanding of cancer heterogeneity, drug resistance and novel therapies and have laid the foundation for international collaborations seeking to leverage cutting-edge approaches in disease modeling.

Prof. Park’s leadership and expertise in bridging the laboratory and clinic have allowed her to build clinical and translational research consortia dedicated to improving outcomes for cancer patients by expanding the reach of precision medicine. These include the Québec Cancer Consortium (QCC), uniting six leading Montreal hospitals, cancer research centres, non-profit and pharmaceutical industry partners. She also co-leads the Québec node of the Terry Fox Research Institute’s Marathon of Hope Network of cancer centres. 

Prof. Park recognized the importance of breast cancer heterogeneity while this was still a very new concept, conducting critical work to establish that high MET levels are associated with triple negative breast cancer (TNBC), an aggressive subtype lacking targeted therapies and subject to a very high rate of relapse and poor clinical outcome. Prof. Park’s group developed some of the first preclinical TNBC models, enabling important discoveries and novel therapeutic strategies.

Among the most important examples of her vision and scientific leadership are her innovative, pioneering studies of the tumor microenvironment. In a technically and conceptually groundbreaking study, Prof. Park and her team defined gene activity signatures specific to tumour cells and to their surrounding normal host cells (the “stroma”) in breast cancer patient samples. The resulting landmark publication established the role of the stroma in determining breast cancer outcome.  

Prof. Park’s further studies of the tumour microenvironment have derived additional gene signatures prognostic of clinical outcome and metastatic progression, established mechanisms of sensitivity to FDA-approved therapies and identified distinct tumor immune microenvironments that associate with outcome in TNBC. Ongoing work in the laboratory is using novel 3D cell printing and single-cell molecular pathology approaches to uncover the mechanisms governing immune cell recruitment and activation in breast and other cancers. 

Throughout her career, Prof. Park has received many illustrious prizes and honours including the Canadian Cancer Society (CCS) Robert L. Noble Prize (2017), the Canadian Society for Molecular Biosciences (CSMB) Arthur Wynne Gold Medal Award (2016) and the Grand Prix Scientifique of the Quebec Breast Cancer Foundation (2019). A fellow of the Royal Society of Canada (2007) and of the Canadian Academy of Health Sciences (2017), she was elected Chair of the American Association for Cancer Research (AACR) Tumor Microenvironment Network (2015-2017).

While the McLaughlin Medal is awarded primarily for research accomplishments, Prof. Park’s remarkable leadership and strategic vision cannot be ignored. She has spent nearly her entire career in positions of leadership at McGill University, serving as Director of the Rosalind and Goodman Cancer Institute since 2013, and has been recognized consistently through academic appointments of the highest level, including a Distinguished James McGill Professorship (2020-present) and the Diane and Sal Guerrera Chair in Molecular Genetics (2003-present).

Nationally, as the Scientific Director of CIHR’s Institute of Cancer Research (2008-13), Prof. Park spearheaded key initiatives on personalized medicine, cancer initiation and progression, the role of lifestyle and the environment. She also co-chaired the Canadian Cancer Research Alliance (CCRA), comprising over 30 cancer research funding agencies, where she led the development of the first Pan-Canadian Cancer Research Strategic Plan. For these and her other efforts she received the CCRA Award for Exceptional Leadership in Cancer Research in 2015.  

In summary, Morag Park has had a unique, powerful and wide-ranging impact on cancer research through the excellence of her own scientific contributions and her exceptional work in defining and implementing a national vision for cancer research.