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Séminaire

Jeudi 21 Décembre 2017
De 11h30 à 13h30
Centre de Recherche - Paris - Amphithéâtre Constant-Burg (12 rue Lhomond, Paris 5e) en visio-conférence avec l'amphithéâtre du bâtiment 111 (Orsay) et salle Clavel (Saint-Cloud)

Ferroptosis: a regulated cell death nexus linking metabolism, redox biology and disease

Abstract: Dr. Stockwell will describe the discovery of ferroptosis, a form of regulated cell death characterized by the iron-dependent accumulation of lethal lipid hydroperoxides.  Current data suggest that ferroptosis is an ancient vulnerability caused by the evolution of cells with polyunsaturated fatty acids in membranes, and that cells have developed complex systems that exploit and defend against this vulnerability. The sensitivity to ferroptosis is dependent on amino acid, iron and polyunsaturated fatty acid metabolism, and the biosynthesis of glutathione, phospholipids, NADPH and coenzyme Q10. Ferroptosis is implicated in the pathological cell death associated with degenerative diseases (e.g. Huntington’s Disease), intracerebral hemorrhage, traumatic brain injury, ischemia-reperfusion injury, and kidney degeneration and may be harnessed for cancer therapy. Mechanisms and therapeutic applications will be described.

Orateur(s)

Dr Brent Stockwell
Professor

Departments of Biological Sciences and Chemistry, Columbia University

Organisateur(s)

M. Yannick Bono

Institut Curie

Invité(e)(s) par

Dr Raphaël Rodriguez
Chef d'équipe
Domain 4 - UMR 3666 / U1143 - Chemical Biology of Membranes and Therapeutic Delivery

Institut Curie

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Dr Raphaël Rodriguez

Chef d'équipe

Institut Curie

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Brent R. Stockwell, Ph.D. is a Professor at Columbia University in the Departments of Biological Sciences and Chemistry. His research involves the discovery of precision medicines that can be used to understand and treat cancer and neurodegeneration, with a focus on mechanisms governing cell death. These interdisciplinary investigations have led to new methods of small molecule drug discovery, and the discovery of drug candidates that act through a new form of cell death. Professor Stockwell has received numerous awards, including a Burroughs Wellcome Fund Career Award at the Scientific Interface, a Beckman Young Investigator Award, an HHMI Early Career Scientist Award, the BioAccelerate NYC Prize, the Lenfest Distinguished Columbia Faculty Award and the Great Teacher of Columbia College Award from the Society of Columbia Graduates. He has trained >100 students, technicians and postdoctoral scientists, published >100 scientific articles, been awarded 14 US patents, and received 42 research grants for >$30 million. He founded the biotechnology companies CombinatoRx Incorporated, Solaris Therapeutics and Kyras Therapeutics, and is the author of The Quest for the Cure: The Science and Stories Behind the Next Generation of Medicines. 

 

Key publications:

 

Yang WS, Kim KJ, Gaschler MM, Patel M, Shchepinov MS, Stockwell BR. Peroxidation of polyunsaturated fatty acids by lipoxygenases drives ferroptosis. Proc Natl Acad Sci USA. 2016 Aug;113(34):E4966-75 [pubmedpdf]

 

Yang WS, Stockwell BR. Ferroptosis: Death by lipid peroxidation. Trends Cell Biol. 2015 Nov [pubmedpdf]

 

Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, Cheah JH, Clemons PA, Shamji AF, Clish CB, Brown LM, Girotti AW, Cornish VW, Schreiber SL, Stockwell BR. Regulation of Ferroptotic Cancer Cell Death by GPX4. Cell 2014 Jan 16; 156(1):317-331 [pubmedpdf]

 

Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R,Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, Morrison B, Stockwell BR. Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death. Cell 2012 May;149(5), 1060-1072 [pubmedpdf]