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Paola Marignani

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Paola A. Marignani
NationalityCanadian
Alma materUniversity of Windsor (H BSc)
University of Western Ontario (MSc)
McMaster University (PhD)
Harvard (Postdoctoral Fellow)
Ivey School of Business (EMBA)
Scientific career
FieldsMolecular Biology, Precision Medicine, Single-cell transcriptomics
InstitutionsDalhousie University
Websitehttps://marignanilab.com/

Paola A. Marignani is a scientist and Full Professor at Dalhousie University in the Faculty of Medicine, Department of Biochemistry and Molecular Biology.[1] She is best known for her research on the tumor suppressor kinase LKB1,[2] and its role in regulating the chromatin remodeling protein SMARCA4 and modeling metabolic processes in breast and lung cancers.[3][4][5]

Biography

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Marignani completed her Hon BSc in Biology from the University of Windsor, followed by an MSc in Neurobiology from the University of Western Ontario.[1] She earned her PhD in Cell Biology from McMaster University. Her postdoctoral training took place at Harvard Medical School in the Division of Signal Transduction followed by the Lunenfeld-Tanenbaum Research Institute and the Ontario Cancer Institute in Toronto, Ontario. She also holds an Executive MBA from the Ivey School of Business at Western University, and a Certificate from MIT Sloan School of Management in Artificial Intelligence in Health Care.[6]

Scientific career

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Marignani is known for research in tumor-suppressing proteins, notably LKB1.[7] In 2001, Marignani discovered the first binding partner of LKB1, specifically SMARCA4, a chromatin remodeling protein.[3] In subsequent studies, Marignani discovered that LKB1 regulates estrogen receptors in breast tissue.[8] Her further research led to the discovery that LKB1 expression in HER2+ breast cancer is reduced or lost.[2] This discovery led to the development of a HER2/ErbB2 mouse model where lkb1 expression was re-engineered.[9] The resulting mice developed mammary tumors quicker than control mice, and the tumors were hyperactive for mTOR and cancer metabolism.[2] Marignani combines technologies such as single-cell transcriptomics and machine learning[10][11] to interrogate disease processes and discover targeted therapies in the framework of precision medicine.[12][6][13][14] 

Marignani also researches disparities in cancer incidence and outcomes within a Black Canadian community in South Shelburne, Nova Scotia.[15] This initiative is part of a broader project funded by the New Frontiers in Research Fund,[16] and seeks to shed light on historical and ongoing systemic issues related to healthcare access and quality.[17]

In addition to funding from Breast Cancer Canada for her research in identifying unique markers associated with HER2+ breast cancer recurrence,[18] Marignani has also been funded by NSERC,[1] CIHR,[2] and the Canadian Foundation for Innovation.[19] She has also been awarded for Excellence in Cancer Research by the Canadian Cancer Society.[20]

Marignani’s earlier research focused on understanding the molecular changes to signaling molecules resulting from polyunsaturated fatty acid incorporation into lipid membranes. She discovered that the integration of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) into lipid membranes altered diacylglycerol profiles in murine macrophages, which could lead to downstream changes in signaling events.[21]

Selected publications

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References

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  1. ^ a b c "Marignani, P. A." Dalhousie University. Retrieved 2024-05-12.
  2. ^ a b c d Andrade-Vieira, Rafaela; Goguen, Donna; Bentley, Heidi A.; Bowen, Chris V.; Marignani, Paola A. (2014-12-30). "Pre-clinical study of drug combinations that reduce breast cancer burden due to aberrant mTOR and metabolism promoted by LKB1 loss". Oncotarget. 5 (24): 12738–12752. doi:10.18632/oncotarget.2818. ISSN 1949-2553. PMC 4350354. PMID 25436981.
  3. ^ a b Marignani, Paola A.; Kanai, Fumihiko; Carpenter, Christopher L. (2001-08-31). "LKB1 Associates with Brg1 and Is Necessary for Brg1-induced Growth Arrest". Journal of Biological Chemistry. 276 (35): 32415–32418. doi:10.1074/jbc.C100207200. PMID 11445556.
  4. ^ "Nova Scotia breast cancer researcher receives $250K grant". Atlantic. 2022-07-18. Retrieved 2024-05-12.
  5. ^ International, Radio Canada (2014-12-15). "Exciting Canadian advance against breast cancer". RCI | English. Retrieved 2024-05-13.
  6. ^ a b "$250,000 Grant to Dr. Paola Marignani to identify HER2+ markers". Breast Cancer Canada. 2022-06-15. Retrieved 2024-05-12.
  7. ^ "Turning off the power: Dr. Paola Marignani finds drug combination that stops growth of breast cancer cells". Dalhousie University. Retrieved 2024-05-12.
  8. ^ Nath-Sain, Suchita; Marignani, Paola A. (2009-04-15). "LKB1 catalytic activity contributes to estrogen receptor alpha signaling". Molecular Biology of the Cell. 20 (11): 2785–2795. doi:10.1091/MBC.E08-11-1138. PMC 2688557. PMID 19369417.
  9. ^ Andrade-Vieira, Rafaela; Xu, Zhaolin; Colp, Patricia; Marignani, Paola A. (2013-02-22). "Loss of LKB1 expression reduces the latency of ErbB2-mediated mammary gland tumorigenesis, promoting changes in metabolic pathways". PLOS ONE. 8 (2): e56567. Bibcode:2013PLoSO...856567A. doi:10.1371/JOURNAL.PONE.0056567. PMC 3579833. PMID 23451056.
  10. ^ Jussinoja, Kaija. "Meet the local scientist changing the narrative for cancer". The Coast Halifax. Retrieved 2024-05-12.
  11. ^ Persaud, Christine (2023-03-24). "Q&A With Kimberly Carson, CEO, Breast Cancer Canada". Wifi Hifi Magazine. Retrieved 2024-08-01.
  12. ^ "LKB1 Tumour Suppressor kinase". Marignani Discovery Research Laboratory. 2017-07-24. Retrieved 2024-05-12.
  13. ^ Kim, Jinhong; Xu, Zhaolin; Marignani, Paola A. (2021-10-15). "Single-cell RNA sequencing for the identification of early-stage lung cancer biomarkers from circulating blood". npj Genomic Medicine. 6 (1): 87. doi:10.1038/s41525-021-00248-y. ISSN 2056-7944. PMC 8519939. PMID 34654834.
  14. ^ Kim, Jinhong; Marignani, Paola A. (2022), Christian, Sherri L. (ed.), "Single-Cell RNA Sequencing Analysis Using Fluidigm C1 Platform for Characterization of Heterogeneous Transcriptomes", Cancer Cell Biology, vol. 2508, New York, NY: Springer US, pp. 261–278, doi:10.1007/978-1-0716-2376-3_19, ISBN 978-1-0716-2375-6, PMID 35737246, retrieved 2024-05-12
  15. ^ Cameron, Josefa (2023-07-01). "Communities hope new panel will help shed light on historical environmental racism". CBC. Retrieved 2024-07-30.
  16. ^ "Feds boost high‑risk, high‑reward research at Dal with New Frontiers funding". Dalhousie News. Retrieved 2024-07-30.
  17. ^ Waldron, Ingrid; Daniel, Juliet (2021-07-08). "Environmental racism: New study investigates whether Nova Scotia dump boosted cancer rates in nearby Black community". The Conversation. Retrieved 2024-07-30.
  18. ^ bcsc2022 (2022-06-15). "$250,000 Grant to Dr. Paola Marignani to identify HER2+ markers". Breast Cancer Canada. Retrieved 2024-07-30.{{cite web}}: CS1 maint: numeric names: authors list (link)
  19. ^ cognit.ca https://cognit.ca/en/facility/fb306b04b6. Retrieved 2024-07-30. {{cite web}}: Missing or empty |title= (help)
  20. ^ cancer, Canadian Cancer Society / Société canadienne du. "Atlantic Caner Research Grant Competition Results". Canadian Cancer Society. Retrieved 2024-07-30.
  21. ^ Marignani, Paola A.; Epand, Richard M.; Sebaldt, Rolf J. (1996-08-14). "Acyl Chain Dependence of Diacylglycerol Activation of Protein Kinase C Activity in vitro". Biochemical and Biophysical Research Communications. 225 (2): 469–473. doi:10.1006/bbrc.1996.1196. PMID 8753785.