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Séminaire

Lundi 18 Novembre 2024
11h
Centre de recherche - Paris - Amphithéâtre Constant-Burg - 12 rue Lhomond, Paris 5e

THE NEUTROPHIL NUCLEUS AS A SIGNALING HUB DURING CHEMOTAXIS AND DNA RELEASE

Research in the Parent lab aims at understanding the mechanisms by which cells reach sites of infection and injury. In particular, our work focuses on neutrophils, the most abundant leukocyte in human blood and first line of defense against insult. We found that, in response to primary chemoattractants, neutrophils secrete the secondary chemoattractant leukotriene B4 (LTB4), which dramatically amplifies the recruitment range of neutrophils to sites of infection or injury. LTB4 is synthesized from the cytosolic phospholipase 2 alpha (cPLA2α)-mediated release of arachidonic acid through the action of the cytosolic enzyme 5-lipoxygenase (5-LO), the endoplasmic reticulum/nuclear envelope-resident protein 5-lipoxygenase activating protein (FLAP) and leukotriene A4 hydrolase. Neutrophil activation triggers the packaging of the LTB4 synthesizing machinery within nuclear envelope-derived multivesicular bodies, which release exosomes that secrete LTB4 to recruit distant neutrophils to infected/injured sites. We also found that chemotaxing neutrophils release nuclear DNA in a non-lytic, rapid, and repetitive manner. The packaging of DNA occurs in the lumen of these same nuclear envelope-derived multivesicular bodies. The mechanisms underlying this response as well as its physiological consequence will be presented.

Orateur(s)

Carole Parent
Professor of Cancer Biology and Pharmacology Professor of Cell and Developmental Biology Research Professor

Raymond and Lynne Ruddon Collegiate, Life Sciences Institute, University of Michigan

Invité(e)(s) par

Ana Maria Lennon

Institut Curie

Matthieu Piel

Institut Curie

Contact

Sylvia Trival

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En bref

Dr.Carole A. Parent obtained B.Pharm. and M.Sc. degrees from the Université of Montreal and a Ph.D. degree from the University of Illinois at Chicago. After completing a postdoctoral fellowship in the laboratory of Dr. Peter N. Devreotes in the Department of Biological Chemistry of the Johns Hopkins University School of Medicine, Dr. Parent joined the Laboratory of Cellular and Molecular Biology at the National Cancer Institute (NCI). She received tenure in 2006, was appointed Deputy Chief in 2010, and Deputy Director of the Center for Cancer Research at the NCI in 2016. Dr. Parent moved to the University of Michigan in 2017 as the inaugural Raymond and Lynne Ruddon Collegiate Professor in Cancer Biology and Pharmacology. She is jointly appointed in the Department of Cell & Developmental Biology. Her laboratory is housed in the Life Sciences Institute of the University of Michigan, where she is a Research Professor. Her research program focuses on identifying the mechanisms that mediate how neutrophils reach infection and injury as well as tumor sites. To do so, Dr. Parent’s group exploits complementary ex vivo and in vivo model systems, cutting-edge live imaging, and a transdisciplinary approach.

En savoir plus

https://experts.umich.edu/2858-carole-parent/publications