# Paola Marignani

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

## Biography

Marignani completed her Hon BSc in Biology from the University of Windsor, followed by an MSc in Neurobiology from the University of Western Ontario. 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. Marignani is also a scientist mentor at the Creative Destruction Lab and scientific director of the QEII Lung Tumour Bank.

## Scientific career

Marignani is known for research in tumor-suppressing proteins, notably LKB1. In 2001, Marignani discovered the first binding partner of LKB1, specifically SMARCA4, a chromatin remodeling protein. In subsequent studies, Marignani discovered that LKB1 regulates estrogen receptors in breast tissue. Her further research led to the discovery that LKB1 expression in HER2+ breast cancer is reduced or lost. This discovery led to the development of a HER2/ErbB2 mouse model where lkb1 expression was re-engineered. The resulting mice developed mammary tumors quicker than control mice, and the tumors were hyperactive for mTOR and cancer metabolism. Marignani combines technologies such as single-cell transcriptomics and machine learning to interrogate disease processes and discover targeted therapies in the framework of precision medicine.
Marignani also researches disparities in cancer incidence and outcomes within a Black Canadian community in South Shelburne, Nova Scotia. This initiative is part of a broader project funded by the New Frontiers in Research Fund, and seeks to shed light on historical and ongoing systemic issues related to healthcare access and quality.
In addition to funding from Breast Cancer Canada for her research in identifying unique markers associated with HER2+ breast cancer recurrence, Marignani has also been funded by NSERC, CIHR, and the Canadian Foundation for Innovation. She has also been awarded for Excellence in Cancer Research by the Canadian Cancer Society.
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.

## Selected publications

* Jinhong Kim; Paola A. Marignani (2022). "Single-Cell RNA Sequencing Analysis Using Fluidigm C1 Platform for Characterization of Heterogeneous Transcriptomes". Methods in Molecular Biology: 261–278. doi:10.1007/978-1-0716-2376-3_19. ISSN 1064-3745. Wikidata Q125798347.
* Jinhong Kim; Zhaolin Xu; Paola A Marignani (15 October 2021). "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. Wikidata Q112643227.
* Ava Vila-Leahey; Sharon A Oldford; Paola A Marignani; Jun Wang; Ian D Haidl; Jean S Marshall (10 March 2016). "Ranitidine modifies myeloid cell populations and inhibits breast tumor development and spread in mice". OncoImmunology. 5 (7): e1151591. doi:10.1080/2162402X.2016.1151591. ISSN 2162-4011. PMC 5006904. PMID 27622015. Wikidata Q37222105.
* Rafaela Andrade-Vieira; Donna Goguen; Heidi A Bentley; Chris V Bowen; Paola A Marignani (1 December 2014). "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. Wikidata Q35149656.
* Rafaela Andrade-Vieira; Zhaolin Xu; Patricia Colp; Paola A Marignani (22 February 2013). "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. ISSN 1932-6203. PMC 3579833. PMID 23451056. Wikidata Q34602408.
* Suchita Nath-Sain; Paola A Marignani (15 April 2009). "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. ISSN 1059-1524. PMC 2688557. PMID 19369417. Wikidata Q37207745.
* Kristine D Scott; Suchita Nath-Sain; Meghan D Agnew; Paola A Marignani (1 June 2007). "LKB1 catalytically deficient mutants enhance cyclin D1 expression". Cancer Research. 67 (12): 5622–5627. doi:10.1158/0008-5472.CAN-07-0762. ISSN 0008-5472. PMID 17575127. Wikidata Q53545879.
* P A Marignani; F Kanai; C L Carpenter (31 August 2001). "LKB1 associates with Brg1 and is necessary for Brg1-induced growth arrest". Journal of Biological Chemistry. 276 (35): 32415–8. doi:10.1074/JBC.C100207200. ISSN 0021-9258. PMID 11445556. Wikidata Q28205561.
* P A Marignani; C L Carpenter (9 July 2001). "Vav2 is required for cell spreading". Journal of Cell Biology. 154 (1): 177–86. doi:10.1083/JCB.200103134. ISSN 0021-9525. PMC 2196856. PMID 11448999. Wikidata Q24654126.
* F Kanai; P A Marignani; D Sarbassova; et al. (15 December 2000). "TAZ: a novel transcriptional co-activator regulated by interactions with 14-3-3 and PDZ domain proteins". The EMBO Journal. 19 (24): 6778–91. doi:10.1093/EMBOJ/19.24.6778. ISSN 0261-4189. PMC 305881. PMID 11118213. Wikidata Q24290626.