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DTSTART;TZID=America/Detroit:20260331T120000
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DTSTAMP:20260422T051048
CREATED:20251030T142900Z
LAST-MODIFIED:20260223T192450Z
UID:33289-1774958400-1774962000@www.vai.org
SUMMARY:Daniel Schramek\, Ph.D.\, M.D. – VAI Seminar Series
DESCRIPTION:Decoding Aneuploidies – using CRISPR technologies in mice to unravel novel cancer driver genes in recurrent CNA\nChromosome instability is highly prevalent in cancer and drives large scale chromosomal imbalances\, known as aneuploidies. How aneuploidy contributes to tumorigenesis remains difficult to study due to the vast numbers of genes affected. Here\, we established a CRISPR Knock Out and Activation Linked Assay (CRISPR-KOALA)\, enabling high-throughput bidirectional genetic screens in immune-competent mouse models of cancer. We developed a compendium of the ten most frequent human chromosome arm-level alterations in basal-like breast cancer (BLBC)\, a disease type driven by large copy number alterations (CNAs).  Using CRISPR-KOALA\, we screened the mouse orthologs of all 3\,752 genes on these arms and identified 90 cancer driver genes\, the vast majority of which have hitherto unknown functions in cancer. These genes drive distinct signalling pathways including MAPK\, Hippo and WNT\, reflecting the high degree of BLBC heterogeneity. Manipulating the identified cancer driver genes overcomes the need for CNAs in p53-mutant BLBC mouse models. Mechanistically\, we uncover PLGRKT as a potent oncogene that lies on chromosome 9p and show that its tumor-promoting activity is associated with highly stress-resistant mitochondria and an increased capacity to detoxify reactive oxygen species. Together\, our findings reveal that arm-level CNAs can function to select specific driver genes to promote heterogeneous biological processes. \nSpeaker Information: \nDaniel Schramek\, Ph.D.\, M.D.\nLunenfeld-Tanenbaum Research Institute \nHost: \nNatasha Zandstra\, Ph.D. Candidate\, VAI Graduate School \nIf you’d like to learn more about Dr. Schramek and his research\, please visit: https://www.lunenfeld.ca/?page=schramek-daniel
URL:https://www.vai.org/event/daniel-schramek-ph-d-m-d-vai-seminar-series/
LOCATION:Van Andel Institute\, 333 Bostwick Ave. NE\, Grand Rapids\, MI\, 49503\, United States
CATEGORIES:Scientific Events,Seminars
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