Rosalind and Morris
Goodman Cancer
Institute Principal
Investigators
Prof. Morag Park’s lab focuses on:
- The molecular and cellular biology of the receptor tyrosine kinase and proto-oncogene MET, its functions and regulation in normal and malignant cells;
- The composition, organization and functional roles of the tumour microenvironment, particularly in triple negative breast cancer (TNBC).
Receptor tyrosine kinases (RTKs) are recognized as targets of precision medicine in human cancer upon their constitutive activation or gene amplification, resulting in dysregulated downstream signaling. Dr. Park’s pioneers’ works were the first to identify a novel mechanism for the receptor for hepatocyte growth factor (HGF), MET, and oncogenic activation, involving a fusion of a protein dimerization domain to the Met kinase. Dr. Park’s lab research aims to identify the critical molecular signals regulated by MET and RTKs that contribute to tumour progression, therapeutic resistance, and strategies for therapeutic interventions.
Park Lab’s research goals have evolved to a broader interest in understanding how multiple genetic alterations and epigenetic events synergize to promote oncogenic transformation and tumour progression. This research interest will interface with a breast cancer translational research initiative formed through a collaboration with multiple basic researchers at McGill and the MUHC and with surgeons, oncologists, and pathologists at the MUHC. Dr. Park and colleagues are forming the Montreal breast cancer Functional Genomics Group which employs the recent advance in strategies of genomics and proteomics from the McGill-based and worldwide research community to identify molecular determinants of tumour progression and response to therapies. This colossal project aims to interface developing technologies in the long term with improved patient care.
We employ the recent advances in strategies of genomics and proteomics from the McGill-based and worldwide research community to identify molecular determinants of tumour prognosis, diagnosis, and response to therapies using patient-derived xenografts (PDXs) and organoid from breast, lung, and gastric cancers. Our lab uses cutting-edge technologies, including single-cell RNA-Sequencing, Visium 10X Genomics, Imaging Mass Cytometry, 3D bio-printing, Bio-ID, transgenic and immune-competent mouse models, and a biobank of patient samples, to unveils critical mechanisms implicated in cancer progression and therapeutic resistance.
What we are
currently
working on
Accumulating evidence support the concept that the deregulated activation of growth factor receptors sustains the malignant behavior of tumour cells. Over the past decades, our work has uncovered an important regulator of invasive cell growth, the Met receptor tyrosine kinase (RTK). Under physiological contexts, Met relays signal from the cell surface to regulate tissue organization by controlling wound healing, morphogenesis, and embryogenesis. However, alteration of these pathways in cancer cells leads to enhanced cell invasion, which is the first step of metastasis. My lab has focused on and will continue to address these questions using the Met receptor tyrosine kinase and oncogene as a model. We focus on signals required for cell transformation, cell invasion, and tumourigenesis.
My lab is also interested by the complex role of the tumour microenvironment (TME) in cancer progression and therapeutic resistance. Tumour cells can recruit cells from the TME and stroma, such as tumour infiltrating lymphocytes (TILs), fibroblasts, and macrophages. A growing body of evidence supports that these cells can enhance cancer cells proliferation and survival and impede anti-tumour immunity, supporting tumour progression, metastatic colonization, and resistance to therapies.
We aim to identify what signal transduction pathways are critical for the development of cancers and how these can be targeted with therapies. This complex question requires a complete understanding of how signals are integrated in normal cells and how these signals become altered in tumour cells in the context of other genetic alterations, as well as specific TME supporting these transformations events.
- Ciblage du RTK MET dans les cancers Les récepteurs à tyrosine kinase (RTK) sont des moteurs majeurs des cancers humains et des cibles thérapeutiques importantes. La dérégulation de MET, le RTK du facteur de croissance des hépatocytes (HGF), favorise l'initiation, le maintien et la progression métastatique de plusieurs cancers solides. Le développement récent de thérapies à base de petites molécules et d'anticorps ciblant MET a conduit à de nombreux essais cliniques, offrant de nouvelles options thérapeutiques pour les patients atteints de cancer. Différents modes de dérégulation oncogénique de MET, notamment l'amplification de MET, l'épissage (délétion de l'exon 14 de Met) et les mutations ponctuelles, favorisent l'activation différentielle de voies en aval pour contrôler les réponses transcriptionnelles et biologiques, conduisant à une augmentation de la pluripotence, de l'invasion et de la prolifération. En combinant la transcriptomique, la Bio-ID, les tests d'invasion en 3D et l'utilisation d'échantillons de patients, mon laboratoire vise à identifier les voies de signalisation essentielles à l'invasion cellulaire, à la progression tumorale et au développement de métastases, ainsi qu'à disséquer les signaux favorisant la résistance thérapeutique. Targeting the MET RTK in cancers Receptor tyrosine kinases (RTK) are major drivers of human cancers and prominent therapeutic targets. Dysregulation of MET, the hepatocyte growth factor (HGF) RTK, promotes initiation, maintenance, and metastatic progression of multiple solid cancers. The recent development of small molecule and antibody-based therapies targeting MET has led to numerous clinical trials, providing new therapeutic options for cancer patients. Different modes of oncogenic MET dysregulation, including MET amplification, splicing (Met exon 14 deletion), and point mutations, promote differential activation of downstream pathways to control transcriptional and biological responses, leading to enhance stemness, invasion, and proliferation. By combining transcriptomic, Bio-ID, 3D invasion assays, and the use of patient specimens, my lab aims at identifying signaling pathways essential for cell invasion, tumour progression, and metastasis and dissecting signals that promote therapeutic resistance.
- Le microenvironnement tumoral dans l'initiation tumorale, la progression du cancer et la résistance thérapeutique En 1999, nous avons lancé le groupe de génomique fonctionnelle du cancer du sein (BCFGG) et nous avons mis en banque plus de 2 500 échantillons de cancer du sein avec des bases de données associées, notamment des données cliniques et pathologiques, des résultats et des réponses aux traitements. Au fil des ans, nous avons caractérisé moléculairement plus de 1 000 échantillons par des profils d'ARNm. L'un de nos intérêts est de décrypter les interactions entre le microenvironnement tissulaire et les cellules cancéreuses, notamment dans des sous-types rares et agressifs de cancer du sein tels que les cancers du sein triple négatifs, les cancers immuno-froids et les mauvais répondants thérapeutiques. Plus récemment, nous nous sommes concentrés sur le développement de biobanques vivantes et avons établi une cohorte unique de xénogreffes dérivées de patients (PDX) et d'organoïdes pertinents pour étudier l'hétérogénéité, la progression et la réponse aux médicaments du cancer du sein. Dans le cadre de cette biobanque vivante, nous avons également développé des lymphocytes associés aux tumeurs (LAT), des fibroblastes associés au cancer (FAC) et des lignes cellulaires dérivées de patients. À l'aide de nos modèles précliniques, nous intégrons la génomique fonctionnelle, les technologies d'impression bio-3D, les cribles à haut débit (2D et 3D), la transcriptomique spatiale et l'imagerie spatiale multiplex, pour comprendre le cancer du sein et identifier de nouvelles vulnérabilités thérapeutiques. The tumour microenvironment in tumour initiation, cancer progression and therapeutic resistance In 1999, we started the Breast Cancer Functional Genomics Group (BCFGG) and banked over 2,500 breast cancer samples with linked databases, including clinical and pathological data, outcome, and response to therapy. Over the years, we molecular characterized by mRNA profiles over 1000 samples. One of our interests is deciphering the interplay of the tissue microenvironment and cancer cells, especially in rare and aggressive breast cancer subtypes such as Triple-negative breast cancer, immune-cold, and poor therapeutic responders. More recently, we have focused on developing live biobanks and established a unique cohort of relevant preclinical patient-derived xenografts (PDX) and organoids to study breast cancer heterogeneity, progression, and drug response. As part of this live biobank, we also developed matched tumour associate lymphocytes (TILs), Cancer-associated Fibroblast (CAFs), and patient-derived cell lines. Using our preclinical models, we integrate functional genomics, 3D bio-printing technologies, high throughput screens (2D and 3D), spatial transcriptomics, and multiplex spatial imaging, to understand breast cancer and identify new therapeutic vulnerabilities.
- Director of the Rosalind and Goodman Cancer Institute (2013-present)
- Distinguished James McGill Professorship (2020-present),
- Departments of Oncology, Biochemistry and Medicine Diane and Sal Guerrera Chair in Molecular Genetics (2003-present).
- Co-Principal Investigator of the Reseau du recherche en cancer (RRCancer), a Quebec-wide cancer biobanking network of clinicians and researchers funded by the FRQS.
- Leader of the Québec Cancer Consortium (QCC), uniting six leading Montreal hospitals, cancer research centres, non-profit and pharmaceutical industry partners with $29M in funding from the Quebec government (MEIE) and partners.
- Co-leader of the Québec node of the Terry Fox Research Institute’s Marathon of Hope Network of cancer centres.
- Served as the Scientific Director of the CIHR Institute of Cancer Research (2008-13) Served as the Director of the McGill Molecular Oncology Group (2006-8) and Joint Head of the Cancer Axis at MUHC Served as the co-chair of the Canadian Cancer Research Alliance (2008-2010) Canada Foundation for Innovation Board of Directors
Our team
- Carol Zhou Étudiant.e de premier cycle Undergraduate Student
- Hong Zhao Assistant.e de recherche Research Assistant
Abdulhameed Al-Ghabkari Candidat.e postdoctoral.e Postdoctoral Fellow 
Anne-Marie Fortier Associée de recherche Research Associate 
Jason Topolski Étudiant.e de premier cycle Undergraduate Student 
Dongmei Zuo Assistant.e de recherche Research Assistant 
Hellen Kuasne Associé.e de recherche Research Associate 
Isabella Pecora Étudiante à la maîtrise MSc Student 
Promita Ghosh Étudiant.e au doctorat PhD Student 
Sandrine Busque Étudiant.e au doctorat PhD Student 
Stephanie Duhamel Chercheur associé Research Associate - Margarita Souleimanova Assistant.e de recherche Research Assistant
- Owen Tang Étudiant.e de premier cycle Undergraduate Student
- Vanessa Brien Étudiant.e de premier cycle Undergraduate Student
- Yuliang Wang Étudiant.e au doctorat PhD Student
Major discoveries
- 2008 Stromal gene expression predicts clinical outcome in breast cancer
- 2013 Met synergizes with p53 loss to induce mammary tumours that possess features of claudin-low breast cancer.
- 2017 A Targetable EGFR-Dependent Tumour-Initiating Program in Breast Cancer.
- 2019 LC3C-mediated autophagy selectively regulates the Met RTK and HGF-stimulated migration and invasion.
- 2019 Spatially distinct tumour immune microenvironments stratify triple-negative breast cancers.
- 2020 Chemogenomic profiling of breast cancer patient-derived xenografts reveals targetable vulnerabilities for difficult-to-treat tumours.
- 2021 Co-dependency for MET and FGFR1 in basal triple negative breast cancers.
- 2022 Endosomal LC3C-pathway selectively targets plasma membrane cargo for autophagic degradation.
Research Partners
Get in touch
1160 Pine Avenue W.
Montreal, Quebec H3A 1A3
Office: Room 602
Lab: Room 511
T. 514 398-5749
T. 514 398-5074
F. 514 398-6769
morag.park@mcgill.ca
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