Paola Marignani

Last updated
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
Fields Molecular Biology, Precision Medicine, Single-cell transcriptomics
Institutions Dalhousie University
Website https://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]

Contents

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. [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] Marignani is also a scientist mentor at the Creative Destruction Lab. [7]

Scientific career

Marignani is known for research in tumor-suppressing proteins, notably LKB1. [8] 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. [9] 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. [10] 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 [11] [12] to interrogate disease processes and discover targeted therapies in the framework of precision medicine. [13] [6] [14] [15]  

Marignani also researches disparities in cancer incidence and outcomes within a Black Canadian community in South Shelburne, Nova Scotia. [16] This initiative is part of a broader project funded by the New Frontiers in Research Fund, [17] and seeks to shed light on historical and ongoing systemic issues related to healthcare access and quality. [18]

In addition to funding from Breast Cancer Canada for her research in identifying unique markers associated with HER2+ breast cancer recurrence, [19] Marignani has also been funded by NSERC, [1] CIHR, [2] and the Canadian Foundation for Innovation. [20] She has also been awarded for Excellence in Cancer Research by the Canadian Cancer Society. [21]

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. [22]

Selected publications

Related Research Articles

<span class="mw-page-title-main">Breast cancer</span> Cancer that originates in mammary glands

Breast cancer is a cancer that develops from breast tissue. Signs of breast cancer may include a lump in the breast, a change in breast shape, dimpling of the skin, milk rejection, fluid coming from the nipple, a newly inverted nipple, or a red or scaly patch of skin. In those with distant spread of the disease, there may be bone pain, swollen lymph nodes, shortness of breath, or yellow skin.

Autocrine signaling is a form of cell signaling in which a cell secretes a hormone or chemical messenger that binds to autocrine receptors on that same cell, leading to changes in the cell. This can be contrasted with paracrine signaling, intracrine signaling, or classical endocrine signaling.

<span class="mw-page-title-main">Trastuzumab</span> Medication

Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2 receptor positive. It may be used by itself or together with other chemotherapy medication. Trastuzumab is given by slow injection into a vein and injection just under the skin.

<span class="mw-page-title-main">HER2</span> Mammalian protein found in humans

Receptor tyrosine-protein kinase erbB-2 is a protein that normally resides in the membranes of cells and is encoded by the ERBB2 gene. ERBB is abbreviated from erythroblastic oncogene B, a gene originally isolated from the avian genome. The human protein is also frequently referred to as HER2 or CD340.

The ErbB family of proteins contains four receptor tyrosine kinases, structurally related to the epidermal growth factor receptor (EGFR), its first discovered member. In humans, the family includes Her1, Her2 (ErbB2), Her3 (ErbB3), and Her4 (ErbB4). The gene symbol, ErbB, is derived from the name of a viral oncogene to which these receptors are homologous: erythroblastic leukemia viral oncogene. Insufficient ErbB signaling in humans is associated with the development of neurodegenerative diseases, such as multiple sclerosis and Alzheimer's disease, while excessive ErbB signaling is associated with the development of a wide variety of types of solid tumor.

Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out by 1) covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, and 2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes. Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several cancers.

Triple-negative breast cancer (TNBC) is any breast cancer that either lacks or shows low levels of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) overexpression and/or gene amplification. Triple-negative is sometimes used as a surrogate term for basal-like.

<span class="mw-page-title-main">SMARCA4</span> Protein-coding gene in the species Homo sapiens

Transcription activator BRG1 also known as ATP-dependent chromatin remodeler SMARCA4 is a protein that in humans is encoded by the SMARCA4 gene.

<span class="mw-page-title-main">STK11</span> Protein-coding gene in the species Homo sapiens

Serine/threonine kinase 11 (STK11) also known as liver kinase B1 (LKB1) or renal carcinoma antigen NY-REN-19 is a protein kinase that in humans is encoded by the STK11 gene.

<span class="mw-page-title-main">LYK5</span> Protein-coding gene in the species Homo sapiens

Protein kinase LYK5, also known as LYK5 or STRADα, is a human protein and also denotes the gene encoding it.

A CDK inhibitor is any chemical that inhibits the function of CDKs. They are used to treat cancers by preventing overproliferation of cancer cells. The US FDA approved the first drug of this type, palbociclib (Ibrance), a CDK4/6 inhibitor, in February 2015, for use in postmenopausal women with breast cancer that is estrogen receptor positive and HER2 negative. While there are multiple cyclin/CDK complexes regulating the cell cycle, CDK inhibitors targeting CDK4/6 have been the most successful; four CDK4/6 inhibitors have been FDA approved. No inhibitors targeting other CDKs have been FDA approved, but several compounds are in clinical trials.

Wafik El-Deiry is an American physician and cancer researcher who is the Associate Dean for Oncologic Sciences at the Warren Alpert Medical School, Brown University, Director of the Cancer Center at Brown University, and the Director of the Joint Program in Cancer Biology at Brown University and its affiliated hospitals. He was previously deputy director of Translational Research at Fox Chase Cancer Center, where he was also co-Leader of the Molecular Therapeutics Program.

mTOR inhibitors Class of pharmaceutical drugs

mTOR inhibitors are a class of drugs used to treat several human diseases, including cancer, autoimmune diseases, and neurodegeneration. They function by inhibiting the mammalian target of rapamycin (mTOR), which is a serine/threonine-specific protein kinase that belongs to the family of phosphatidylinositol-3 kinase (PI3K) related kinases (PIKKs). mTOR regulates cellular metabolism, growth, and proliferation by forming and signaling through two protein complexes, mTORC1 and mTORC2. The most established mTOR inhibitors are so-called rapalogs, which have shown tumor responses in clinical trials against various tumor types.

mIR489 Non-coding RNA in the species Homo sapiens

MicroRNA 489 is a miRNA that in humans is encoded by the MIR489 gene.

Dr. Fayaz Ahmad Malik is an Indian pharmacologist, cancer biologist and a scientist at the Indian Institute of Integrative Medicine of the Council of Scientific and Industrial Research. He is known for his studies on investigating the regulatory mechanisms of Cancer Stem Cells during tumor metastasis. His studies also involve the identification of signaling networks conferring resistance to current anti-cancer therapies. His discovery of new anticancer agents holds a number of patents for the processes he has developed. The Department of Biotechnology of the Government of India awarded him the National Bioscience Award for Career Development, one of the highest Indian science awards, for his contributions to Biosciences, in 2014.

Jean Sylvia Marshall, born in Birmingham, England, is a Canadian immunologist and acting Professor and Head of the Department of Microbiology & Immunology at Dalhousie University in Halifax, Nova Scotia, Canada. Marshall's work has investigated how mast cells are involved in the early immune response to infection and antigen. She is best known for her discovery of the previously unknown degranulation-independent immunoregulatory roles of mast cells in infection and allergy and their ability to mobilize dendritic cells.

Endocrine therapy is a common treatment for estrogen receptor positive breast cancer. However, resistance to this therapy can develop, leading to relapse and progression of disease. This highlights the need for new strategies to combat this resistance.

<span class="mw-page-title-main">Mary L. Disis</span> American physician

Mary L. "Nora" Disis is an American physician-oncologist and the editor in chief of JAMA Oncology.

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Valerie M. Weaver is a professor and the director of the Center for Bioengineering and Tissue Regeneration in the department of surgery and co-director Bay Area Center for Physical Sciences and Oncology at the University of California San Francisco (USA). She has been working and leading oncology research for more than 20 years. Her scientific contributions have been recognised by different awards. She was the first woman to receive the Shu Chien Award from the Biomedical Engineering Society in 2022, which honours contributions in the cellular and molecular bioengineering field.

References

  1. 1 2 3 "Marignani, P. A." Dalhousie University. Retrieved 2024-05-12.
  2. 1 2 3 4 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. 1 2 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. 1 2 "$250,000 Grant to Dr. Paola Marignani to identify HER2+ markers". Breast Cancer Canada. 2022-06-15. Retrieved 2024-05-12.
  7. "Paola Marignani". Creative Destruction Lab. Retrieved 2024-11-20.
  8. "Turning off the power: Dr. Paola Marignani finds drug combination that stops growth of breast cancer cells". Dalhousie University. Retrieved 2024-05-12.
  9. 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.
  10. 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.
  11. Jussinoja, Kaija. "Meet the local scientist changing the narrative for cancer". The Coast Halifax. Retrieved 2024-05-12.
  12. Persaud, Christine (2023-03-24). "Q&A With Kimberly Carson, CEO, Breast Cancer Canada". Wifi Hifi Magazine. Retrieved 2024-08-01.
  13. "LKB1 Tumour Suppressor kinase". Marignani Discovery Research Laboratory. 2017-07-24. Retrieved 2024-05-12.
  14. 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.
  15. 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
  16. Cameron, Josefa (2023-07-01). "Communities hope new panel will help shed light on historical environmental racism". CBC. Retrieved 2024-07-30.
  17. "Feds boost high‑risk, high‑reward research at Dal with New Frontiers funding". Dalhousie News. Retrieved 2024-07-30.
  18. 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.
  19. 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)
  20. cognit.ca https://cognit.ca/en/facility/fb306b04b6 . Retrieved 2024-07-30.{{cite web}}: Missing or empty |title= (help)
  21. cancer, Canadian Cancer Society / Société canadienne du. "Atlantic Caner Research Grant Competition Results". Canadian Cancer Society. Retrieved 2024-07-30.
  22. 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.