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X-WR-CALNAME:FGSL Webinar: Single-cell Intercellular CRISPR Screen Revea
 ls Stromal Regulators of Colorectal Cancer Plasticity
X-WR-CALDESC:The Milner Therapeutics Institute
X-WR-TIMEZONE:Europe/London
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SUMMARY:FGSL Webinar: Single-cell Intercellular CRISPR Screen Reveals St
 romal Regulators of Colorectal Cancer Plasticity
DESCRIPTION:&#x1f5d3\;&#xfe0f\; 14 April\n&#x23f0\; 11:00am-12:00pm\n&#
 x1f4cd\; Online\n\nJoin the Functional Genomics Screening Laboratory (F
 GSL) team as we welcome Corinne Molyneux for this special webinar.\n\nS
 peaker: Corinne Molyneux\, University College London\n\nAbstract: Colore
 ctal cancer (CRC) displays high levels of nongenetic phenotypic plastici
 ty\, allowing cancer cells to dynamically shift between different functi
 ons\, enabling therapy evasion. This is particularly evident in poor pro
 gnosis\, stromal-rich CRC tumours. These tumours also have an elevated p
 resence of revival cancer stem cells (revCSCs). In the microenvironment 
 of these tumours cancer-associated fibroblasts (CAFs) act as dynamic reg
 ulators driving the reversible acquisition of YAP-dependant\, slow-cycli
 ng\, chemoresistant features that define the revCSC state. The soluble f
 actors that are regulating this transition were however undefined.\n\nTo
  resolve this question\, we developed a high-throughput single-cell CRIS
 PR assay to systematically perturb the CAF secretome when in direct co-c
 ulture with patient derived organoids (PDO). Individual components of th
 e secretome were targeted by synthetic gRNAs in Cas9 expressing CAFs bef
 ore co-culture. The perturbed co-cultures were then assessed via multipl
 exed mass cytometry\, capturing cell fate markers\, post-translational m
 odification (PTM) signalling\, cell-cycle activity\, and apoptosis in bo
 th PDOs and CAFs at single-cell resolution.\n\nUsing this platform we ha
 ve successfully targeted 202 ligands in our PDO+CAF model and quantified
  the role of each in the revCSC transition\, unveiling the primary effec
 tor of stromal-induced CRC plasticity changes. These findings demonstrat
 e that CRC phenotypic plasticity is regulated by stromal-derived signals
 \, providing new mechanistic insight into therapy failure and describing
  a potential therapeutic intervention strategy to overcome plasticity dr
 iven chemoresistance.\n\nRegister at: cam-ac-uk.zoom.us/meeting/registe
 r/I4NjVGD2T4Oui4FWDTaJrw#/registration
URL;VALUE=URI:https://www.milner.cam.ac.uk/events/fgsl-webinar-single-ce
 ll-intercellular-crispr-screen-reveals-stromal-regulators-of-colorectal-
 cancer-plasticity/
UID:urn:uuid:1aa904eb-16ae-4676-ad92-c13db6cf5bbe
STATUS:CONFIRMED
ORGANIZER:
DTSTAMP:20260604T105357Z
DTSTART;TZID=Europe/London:20260414T110000
DTEND;TZID=Europe/London:20260414T120000
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