Event Details

Alfred E.Mann Department of Biomedical Engineering - Seminar series

Fri, Mar 14, 2025
11:00 AM - 12:00 PM
Location: RTH 109
Speaker: Sheng Li, Ph. D., Associate Professor in the Department of Cancer Biology at the Keck School of Medicine, University of Southern California. She also serves as the Program Co-Leader of Epigenetic Regulation in Cancer at the USC NCI-designated Norris Comprehensive Cancer Ce

Talk Title: From Aging to Leukemia: Computational Epigenomics of Hematopoietic Stem Cell Fate

Abstract: Aging and epigenetic reprogramming are deeply intertwined in hematopoiesis and leukemogenesis. Our research investigates how genetic and epigenetic alterations shape hematopoietic stem cell (HSC) evolution, clonal expansion, and malignant transformation. First, using our next-generation and long-read sequencing pipelines, we demonstrated that somatic variations in DNA and histone methylation regulators disrupt the DNA methylome, promoting leukemogenesis. Second, we examined how aging alters HSC fate, clonal dynamics, and transcriptional states through genetic barcoding and single-cell RNA sequencing, revealing age-driven shifts in hematopoiesis via in vivo clonal tracing. We also explored how senolytic interventions reshape the aging hematopoietic transcriptome, potentially reversing age-related dysfunction. Finally, clonal hematopoiesis (CH) is an age-associated expansion of mutant hematopoietic stem cells, linked to leukemia and cardiovascular risk. We found that Tet2 deficiency mitigates epigenetic aging, preserving HSC function and assisting clonal expansion. By integrative mining of single-cell RNA sequencing and single-nucleus chromatin accessibility data, we investigated how Tet2 deficiency reprograms the aging epigenome and influences clonal fitness in CH. Together, these findings provide new insights into how aging and epigenetic dysregulation contribute to leukemogenesis and highlight potential therapeutic strategies for mitigating CH and malignant transformation in hematopoietic stem cells.

Biography: Sheng Li, Ph.D., is an Associate Professor in the Department of Cancer Biology at the Keck School of Medicine, University of Southern California. She also serves as the Program Co-Leader of Epigenetic Regulation in Cancer at the USC NCI-designated Norris Comprehensive Cancer Center.  Dr. Li received her PhD in Computational Biology from Cornell University in 2014, where she focused on the computational transcriptomics and epigenomics of leukemia relapse. She then served as an Instructor of Bioinformatics at Weill Cornell Medicine in 2014. In 2016, Dr. Li joined the Jackson Laboratory for Genomic Medicine and was promoted to Associate Professor in 2022. In 2024, her lab moved to the USC Keck School of Medicine. The Li lab focuses on algorithm development and integrative mining of long-read, single-cell, and spatial multi-omics data to understand the impact of cell-to-cell variations – in epigenome and transcriptome – and aged microenvironment in driving cancer evolution. The Li Lab has been embedded in a network of NIH consortia, e.g., NCI-NIA jointly funded OncoAging Consortium, NIH Common Fund Cellular Senescence Network (SetNet) Consortium, and NHGRI funded The Encyclopedia of DNA Elements (ENCODE) Consortium. She co-chairs the Omics and Image-Mapping Working Group in SetNet Consortium since 2022. Dr. Li is a recipient of the NIH Maximizing Investigators' Research Award (2019), the American Association for Cancer Research's "NextGen Star" Award (2020), and the Leukemia and Lymphoma Society Scholar (2024).
 

Host: Peter Wang