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SUMMARY:Reprogramming the reactivity of iron in cancer
DTSTART:20191015T163000
DTEND:20191015T173000
DTSTAMP:20260314T214621Z
UID:bd04529b3734ad1aabcc5695b8eb53a8ac9a8bf3e2ca10e4277098a0
CATEGORIES:Conferences - Seminars
DESCRIPTION:Raphaël Rodriguez\nCD44 is a transmembrane glycoprotein that 
 is linked to various biological processes reliant on the epigenetic plasti
 city of cells\, including development\, inflammation\, immune responses\, 
 wound healing and cancer progression. While thoroughly studied\, functiona
 l regulatory roles of this so-called ‘cell surface marker’ remain elus
 ive. We discovered that CD44 mediates endocytosis of iron interacting with
  hyaluronates in tumorigenic cell lines and primary cancer cells. We found
  that this glycan-mediated iron endocytosis mechanism is enhanced during e
 pithelial-mesenchymal transition (EMT)\, unlike the canonical transferrin-
 dependent pathway. EMT is further characterized by molecular changes requi
 red for iron-catalyzed oxidative demethylation of the repressive histone m
 ark H3K9me2 that governs the expression of mesenchymal genes. CD44 itself 
 is transcriptionally regulated by nuclear iron\, demonstrating a positive 
 feedback loop\, which is in contrast to the negative regulation of transfe
 rrin receptor by excess iron. Finally\, we show that epigenetic plasticity
  can be altered by interfering with iron homeostasis with spatial and temp
 oral resolution using small molecules. This comprehensive study reveals an
  alternative iron uptake mechanism that prevails in the mesenchymal state 
 of mammalian cells\, illuminating a central role of iron as a rate-limitin
 g regulator of epigenetic plasticity.\nSpeaker\nRaphaël Rodriguez carried
  out his PhD studies under the supervision of Sir J. Baldwin at Oxford (UK
 )\, where he completed the total synthesis of complex natural products. He
  joined the University of Cambridge in 2005 as a Cancer Research UK Postdo
 ctoral Fellow\, working under the mentorship of Sir S. Balasubramanian and
  was promoted to Senior Research Associate in 2009. From 2009 to 2012\, he
  trained as a cell biologist under the guidance of Prof. S. Jackson at the
  Gurdon Institute in Cambridge. His studies established a firm link betwee
 n G-quadruplex DNA and genome instability in human cells. In 2012\, he obt
 ained the Habilitation to Direct Research and joined the CNRS as a Princip
 al Investigator. He then moved to Institut Curie in 2015 and was promoted 
 Director of Research in 2017. His team investigates the role of d-block me
 tals in the regulation of cellular plasticity\, the biological process tha
 t enables cells to acquire metastatic and drug resistance properties. Thei
 r recent discovery that mesenchymal cancer cells are addicted to iron prom
 pted the design of a new generation of drugs with controlled cellular loca
 lization. These molecules are able to reprogram the reactivity of iron\, t
 o abolish cellular plasticity and to kill persister cancer cells. He has g
 ained international recognition with key contributions in chemistry and bi
 ology that can impact on human medicine. He co-authored 70 articles\, book
 s and scientific commentaries. He is listed as a co-inventor on several pa
 tents and commercialized 3 biologically active small molecules. He was awa
 rded a competitive ERC consolidator grant\, has been elected Fellow of the
  Royal Society of Chemistry\, was recently nominated Franco-British Young 
 Leaders\, is a recipient of the Tetrahedron Young Investigator Award in Bi
 oorganic and Medicinal Chemistry and has recently received the Grand Prix 
 de l'Institut de France Charles Defforey. He is the scientific co-founder 
 of the biotech company SideROS.
LOCATION:BCH 2201 https://plan.epfl.ch/?room==BCH%202201
STATUS:CONFIRMED
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