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UID:entry-141@www.dkfz.de
DTSTAMP:20260929T163717Z
DTSTART:20260318T090000Z
DTEND:20260318T100000Z
SUMMARY:DDLSS: Liron Bar-Peled "Identification of Druggable and Redox Vulne
 rabilities in Cancer"
DESCRIPTION:Liron is the Rullo Family Endowed Chair for Cancer Research at 
 MGH and an Associate Professor of Medicine in Biological and Biomedical Sc
 iences at Harvard Medical School. He received his Bachelor of Science degr
 ee in Biochemistry from the University of Georgia and his PhD in Biology f
 rom the Massachusetts Institute of Technology\, where he used advanced cel
 lular and molecular techniques to uncover how nutrients are sensed. As a D
 amon Runyon Postdoctoral fellow at the Scripps Research Institute\, he lev
 eraged chemical proteomic technologies to understand how cancer cells resp
 ond to oxidative stress. Having started his lab at the Krantz Family Cente
 r for Cancer Research\, he has made important contributions to understandi
 ng how tumors sense and respond to metabolic stress and identifies new dru
 ggable vulnerabilities by integrating technologies that leverage high-thro
 ughput biochemistry\, chemistry\, and analytics with clinical insights. Li
 ron’s work led to the founding of Scorpion Therapeutics (acquired by Eli
  Lily) and he has been widely recognized in the field as a Pew-Stewart Sch
 olar\, Mark Foundation Emerging Leader Award\, NIH/NCI Merit Award\, V Fou
 ndation Scholar\, MRA young investigator and Damon Runyon Innovator. Prote
 ins that sense intracellular reactive metabolites and regulate their produ
 ction play essential roles in coordinating pathways implicated in human di
 seases\, including cancer and neurodegeneration. Using VPS35 as a model re
 active oxygen species (ROS) sensor\, I demonstrate that oxidation of key V
 PS35 cysteines disrupts Retromer association with endosomal membranes\, tr
 iggers plasma membrane remodeling\, and suppresses mitochondrial translati
 on to limit ROS output. Building on the concept of targeted cysteine oxida
 tion\, we developed molecular COUPLrs—small molecules bearing two cystei
 ne-reactive warheads—together with CONNECT\, an integrated chemical prot
 eomic platform for target deconvolution. Profiling a COUPLr library across
  13 cancer cell lines revealed 118 protein classes that can be chemically 
 coupled\, including mutant-selective complexes. We further engineered an a
 dvanced COUPLr targeting the oncogenic fusion EML4–ALK\, which engages t
 he EML4 domain\, perturbs protein dynamics\, and disrupts downstream signa
 ling. Notably\, COUPLr binding promotes proteasome-mediated degradation of
  EML4–ALK\, a feature shared with ALK-directed drugs converted into COUP
 Lrs. Together\, molecular COUPLrs offer an unbiased strategy to discover s
 mall molecules that selectively target protein complexes. Liron Bar-Peled 
 is seeking scientists (masters\, MD or PhD) with a strong mechanistic mind
 set who are excited to apply high-content\, data-rich approaches to uncove
 r fundamental biochemical and cell biological mechanisms.
LOCATION:Dkfz Communication Center - Lecture Hall
URL:https://www.dkfz.de/en/news/events/details/184-ddlss-liron-bar-peled-id
 entification-of-druggable-and-redox-vulnerabilities-in-cancer/a141
CATEGORIES:Vorträge und Seminare
ORGANIZER;CN="Martina Jochim":mailto:m.jochim@dkfz-heidelberg.de
STATUS:CONFIRMED
SEQUENCE:1790690401
LAST-MODIFIED:20260929T140001Z
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