BEGIN:VCALENDAR
VERSION:2.0
PRODID:-//Memento EPFL//
BEGIN:VEVENT
SUMMARY:EPFL BioE Talks SERIES  "Mechanisms of Androgen Deprivation Therap
 y Induced Lineage Plasticity in Prostate Cancer"
DTSTART:20220404T160000
DTEND:20220404T170000
DTSTAMP:20260919T215414Z
UID:e75092a473a894d12dd1754814f6c97d5e5ed5a1d2e5eb66bc8e5797
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Wouter Karthaus\, ISREC\, School of Life Sciences\, EPFL
 \, Lausanne (CH)\nWEEKLY EPFL BIOE TALKS SERIES\n\nAbstract:\nThe inherent
  plasticity of tumor cells provides a mechanism of resistance to many mole
 cularly targeted therapies\, exemplified by adeno-to-neuroendocrine lineag
 e transitions seen in prostate and lung cancer. Here we investigate the ro
 ot cause of this lineage plasticity in a primary murine prostate organoid 
 model that mirrors the lineage transition seen in patients. These cells lo
 se luminal identity within weeks following deletion of Trp53 and Rb1\, ult
 imately acquiring an Ar-negative\, Syp+ phenotype after orthotopic in vivo
  transplantation. Single-cell transcriptomic analysis revealed progressive
  mixing of luminal-basal lineage features after tumor suppressor gene dele
 tion\, accompanied by activation of Jak/Stat and Fgfr pathway signaling an
 d interferon-a and -g gene expression programs prior to any morphologic ch
 anges. Genetic or pharmacologic inhibition of Jak1/2 in combination with F
 GFR blockade restored luminal differentiation and sensitivity to antiandro
 gen therapy in models with residual AR expression. Collectively\, we show 
 lineage plasticity initiates quickly as a largely cell-autonomous process 
 and\, through newly developed computational approaches\, identify a pharma
 cological strategy that restores lineage identity using clinical grade inh
 ibitors.\n\nBio:\n2007            BSc    Rijksuniversiteit\
 , Groningen (NL)\n2008            MSc    Rijksuniversiteit\
 , Groningen (NL)\n2013            PhD    Hans Clevers group\
 , Molecular Genetics Dept.\, Hubrecht Institute\, Utrecht\, The Netherland
 s\n2014-2022        Research Associate\, Memorial Sloan Kettering C
 ancer Center\, New York City\, NY (USA)\nFrom April 1\, 2022       
  Assistant Professor (Tenure Track)\, ISREC\, EPFL\, Lausanne (CH)\n\n\nZ
 oom link (with one-time registration for the whole series) for attending r
 emotely: https://go.epfl.ch/EPFLBioETalks\n\n\nInstructions for 1st-year P
 h.D. students who are under EDBB’s mandatory seminar attendance rule:\nI
 F you are not attending in-person in the room\, please make sure to\n\n	se
 nd D. Reinhard a note before noon on seminar day\, informing that you plan
  to attend the talk online\, and\n	be signed in on Zoom with a recognizabl
 e user name (not a pseudonym making it difficult or impossible to be ident
 ified).\n\nStudents attending the seminar in-person should collect a confi
 rmation signature after the talk - please print your own signature sheet b
 eforehand (71 kB pdf available for download here).
LOCATION:SV 1717 https://plan.epfl.ch/?room==SV%201717 https://go.epfl.ch/
 EPFLBioETalks
STATUS:CONFIRMED
END:VEVENT
END:VCALENDAR