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DTSTART;TZID=America/New_York:20250926T103000
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DTSTAMP:20260602T001626
CREATED:20250924T162425Z
LAST-MODIFIED:20250924T162425Z
UID:14823-1758882600-1758888000@seasevents.nmsdev7.com
SUMMARY:CBE Doctoral Dissertation Defense: "Mechanical Confinement as a Driver of Aneuploidy in Cancer" (Steven Phan)
DESCRIPTION:Abstract: \n\n\n\nCell confinement and mechanical stress are common in solid tumors\, but any impact on genetic changes remains unclear. Using chromosome reporters (ChReporters) that reveal heritable losses of chromosomes in live cells\, we discover that ChReporter losses are surprisingly equivalent when cells are subjected to either mild confinement (6-10µm) or strong confinement (2µm). Strong confinement causes interphase nuclear rupture in most cells\, whereas mild confinement suffices to perturb mitotic spindles\, prolong pro/metaphase\, and induce micronuclei. However\, micronuclei that form upon chromosome mis-segregation in mitosis do not emerge during mild confinement but do emerge following release – indicating a mitotic memory of the confined state. Live cell imaging post-confinement revealed that mitotic cells and their daughters also tend to arrest or die. Delayed induction of micronuclei and ChReporter loss are phenocopied by transient disruption of microtubules. Inhibition of cell cycle entry using a clinically deployed CDK4/6-inhibitor further shows ChReporter loss requires mitosis and inhibitor washout increases ChReporter loss. Consistent with a memory of spindle confinement\, single cell RNA-sequencing demonstrates enrichment of chromosome segregation factors long after confinement.
URL:https://seasevents.nmsdev7.com/event/cbe-doctoral-dissertation-defense-mechanical-confinement-as-a-driver-of-aneuploidy-in-cancer-steven-phan/
LOCATION:Raisler Lounge (Room 225)\, Towne Building\, 220 South 33rd Street\, Philadelphia\, PA\, 19104\, United States
CATEGORIES:Doctoral,Student,Dissertation or Thesis Defense
ORGANIZER;CN="Chemical and Biomolecular Engineering":MAILTO:cbemail@seas.upenn.edu
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