Chercheur.es principaux
de l'Institut du cancer
Rosalind et Morris
Goodman
La Dre Hannah Garner est membre de l'Institut de recherche sur le cancer Goodman (ICG) et professeure adjointe au Département de microbiologie et d'immunologie à l'Université McGill.
Recherche
en cours
- 1) Understanding and disrupting primary tumour induced skewing of haematopoiesis to reduce metastatic spread Different tumours produce different pro-inflammatory mediators which can lead to different lineage fate decisions. We are working to investigate how different inflammatory signals influence bone marrow output, with a particular focus on the transcription factors that control lineage specification within the myeloid compartment. Using genetically modified mouse models (GEMMs) of breast and ovarian cancer, we aim to understand how primary tumours influence local bone marrow cues that organise and control myelopoiesis. By deepening our understanding of how primary tumours alter control of myelopoiesis, we aim to uncover novel targets for normalising haematopoietic output in tumour-bearing hosts to reduce tumour-induced systemic inflammation and metastatic spread and potentially improve response to immune checkpoint blockade.
- 2) Oestrogen signalling in haematopoiesis Sex differences in the immune system are well documented with females exhibiting stronger immune responses and oestrogen is widely considered to have a “protective” effect in pre-menopausal women against chronic inflammatory conditions. However, this advantage diminishes after menopause, suggesting that hormonal signalling plays an important role. Haematopoietic stem cells (HSCs) express oestrogen receptors (ERs) and oestrogen influences their proliferation, differentiation, and survival of HSCs and progenitor cells. We are working to understand how normal, physiological variations in oestrogen levels impact haematopoiesis, lineage fate decisions and myeloid cell function during an adult biological female’s lifespan. Combining analysis of mouse models and human blood samples, we are exploring how oestrogen-deficiency reshapes immune cell development and can drive tumour-promoting chronic, systemic inflammation. In the future, we will expand our analysis to understand how targeted hormone therapies for ER+ breast cancer (such as aromatase inhibitors) impact the immune system, in particular myeloid cells. This work will provide insights into the intersection of hormonal signalling, immune regulation and cancer progression.
- 3) Long term consequences of myelosuppressive chemotherapy Chemotherapy is widely used to treat breast and ovarian cancer targeting rapidly dividing cells. However, this includes immune progenitors making them highly sensitive to killing by chemotherapeutics. Specifically, myeloid progenitors which continually replenish inflammatory cells such as monocytes and neutrophils are heavily suppressed by many chemotherapeutic agents. In the short-term this myelosuppression can lead to increased risk of bacterial infection. In the long term, immune cell numbers broadly recover, however there is limited data on the long-term functional consequences of this therapy-induced myelosuppression. Emerging evidence suggests that myelosuppressive chemotherapy can induce somatic mutations in hematopoietic stem and progenitor cells (HSPCs) resulting in clonal haematopoiesis (CH). CH is increasingly recognized not only for its association with haematological malignancies but also for its link with immune dysfunction, particularly in the context of inflammatory diseases. However, CH may not be the only mechanism by which myeloablative chemotherapy leads to immune dysfunction. Our research focuses on understanding chemotherapy-induced genetic and epigenetic changes in HSPCs and mammary gland macrophages that lead to breast cancer-promoting local and systemic chronic inflammation. Deeper, mechanistic understanding of the consequences of chemotherapy on inflammatory cells will provide insight to how chemotherapy-induced changes lead to immune dysfunction and provide insight into whether immune dysfunction contributes to resistance to immune checkpoint blockade in heavily pre-treated patients.
Équipe
- Elan Behar Étudiant.e de premier cycle Undergraduate Student
- Lucie Droin Étudiant.e de premier cycle Undergraduate Student
Nos partenaires de recherche
Nous
joindre
1160 ave des Pins O
Montreal, Québec
Office: 415
Lab:
T. 514 396 2850
T.
F.
hannah.garner@mcgill.ca
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