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Abstract: Cellular senescence is a complex state that can either suppress or promote cancer. Because senescence is frequently accompanied by epigenetic changes, we used a zebrafish model of early-stage liver cancer driven by overexpression of the epigenetic regulator UHRF1 to investigate how epigenome reprogramming generates distinct senescent cell states and influences cancer development. Functional studies revealed that cells with different senescence signatures and levels of UHRF1 have distinct cancer-related properties and vulnerabilities. Cells expressing lower levels of UHRF1 can re-enter the cell cycle following loss of tp53 whereas cells with high UHRF1 levels remain arrested and are selectively targeted by the senolytic drug Navitoclax. These findings demonstrate how epigenetic differences can determine the fate of senescent cells and may provide a mechanistic basis for patient stratification and the development of more targeted cancer therapies.

Biography: Dr. Kirsten Sadler (Edepli) is a geneticist and cell biologist whose research explores how epigenetic mechanisms regulate development, regeneration, and disease. She earned a Master’s in Medicine from Harvard Medical School, a Ph.D. from Harvard University, and completed postdoctoral training at MIT, where she used zebrafish to identify genes essential for liver development and disease. Her current work focuses on epigenetics in liver development, regeneration, cancer, and transposon regulation in zebrafish, mice, and octopus, defining how the epigenetic changes caused by oncogenic stimuli and aging deregulate cell proliferation, impair liver function, and block regeneration. A pioneer in using zebrafish to model liver disease and toxicant-induced injury, Dr. Sadler has published over 75 scientific papers and secured significant research funding from US and international funding. In addition to her research accomplishments, she is a committed mentor and advocate for equity in science and has held senior leadership roles at NYU Abu Dhabi focused on faculty development, inclusion, and advancement. Dr. Sadler is a tenured Professor of Biology at NYU Abu Dhabi and a Global Network Professor at NYU. She and her husband have 4 children and live in Abu Dhabi.