Steve Henikoff, PhD
Professor of Basic Sciences - Fred Hutchinson Cancer Center, Seattle
Abstract
Genome-wide hypertranscription is common in human cancer and predicts poor prognosis. To understand how hypertranscription might drive cancer, we applied our CUTAC method for mapping RNA polymerase II (RNAPII) genome-wide in formalin-fixed paraffin-embedded (FFPE) sections. RNAPII occupancy at S-phase-dependent histone genes accurately predicted rapid recurrence of meningiomas and corresponded to total whole-arm chromosome losses. Whole-arm losses alone predicted outcome in RNA-sequencing and whole-genome pan-cancer sequencing data. We propose that elevated RNAPII at histone genes both drives hyper-proliferation and displaces the CENP-A histone H3 variant from centromeres, causing centromere breaks and aneuploidies that shape the selective landscape in cancer progenitor cells. Our experimental investigation of the S-phase-dependent histone genes in flies and humans has uncovered a negative feedback loop that regulates histone gene expression over the cell cycle.
About Steve Henikoff
Steve Henikoff received a BS from the University of Chicago, a PhD from Harvard University and performed post-doctoral work at the University of Washington. He is a professor of Basic Sciences at Fred Hutch, and an affiliate professor of Genome Sciences at the University of Washington. He is also an HHMI investigator, a member of the US National Academy of Sciences and a fellow of both the American Academy of Arts and Sciences and the American Association for the Advancement of Science. He received the Genetics Society of America Medal in 2015, and the 55th Lewis S. Rosenstiel Award for Distinguished Work in Basic Medical Research in 2025. His laboratory performs research on chromatin and nuclear dynamics, transcriptional regulation, centromeres and cancer epigenetics, and develops experimental and computational tools for studying these processes.
Sponsored by the Center for Physical Genomics and Engineering, the Cancer and Physical Sciences Program at the Robert H. Lurie Comprehensive Cancer Center, and NIH Grants T32GM142604 and U54CA268084
Cost: Free, registration required at:
https://tinyurl.com/2rw8n7bt