Date: 7 January 2026 (Wednesday)
Time: 2:00 pm – 3:00 pm
Venue: Mrs Chen Yang Foo Oi Telemedicine Centre, 2/F, William M.W. Mong Block, 21 Sassoon Road
Host: Professor Michael Hӓusser

Dr. Andrew Xiao’s lab is in the Department of Genetics at the Yale University School of Medicine and the Yale Stem Cell Center. Dr. Xiao received his Ph.D. degree from Terry Van Dyke’s lab at UNC-Chapel Hill and completed his postdoctoral training in David Allis’ lab at Rockefeller University.

Dr. Xiao’s laboratory focuses on the role of novel epigenetic mechanisms in pluripotent stem cells, early embryogenesis, and their relevance to human diseases, especially cancer. His lab has made several major discoveries in this direction. Dr. Xiao’s lab discovered that iPS cell quality is mainly controlled by histone variant deposition and function. His laboratory also discovered that epigenetic mechanisms control endogenous transposon expression, the expression of 2C-stage embryonic genes, and telomere length in embryonic stem cells. The Xiao lab has also discovered the critical role of DNA secondary structures and rare DNA modifications in early embryogenesis. His lab is also interested in divergent and conserved epigenetic mechanisms underlying cell fate decisions in early embryogenesis during mammalian evolution.

Furthermore, the Xiao lab has made major contributions to cancer research. Most recently, they discovered novel epigenetic pathways that initiate and maintain oncogene amplification and expression in therapy-resistant human cancers, as well as epigenetic mechanisms controlling the cancer-initiating population. In recognition of these achievements, Andrew Xiao is a recipient of the NCI Howard Temin Award in Cancer Research (K99/R00), the New Scholar Award from the Ellison Medical Foundation, the Yale Outstanding Early Career Investigator Award, the Yale-Blavatnik Innovation Award, an NIH MIRA award, and the Eugene and Carol Ludwig Family Foundation Outstanding Investigator Award.

Although lineage-specific chromatin regulators are thought to orchestrate the gene expression programs that drive early cell fate decisions in mammalian development, few such factors have been defined—especially in humans, where mechanistic studies are limited by ethical and technical constraints. This gap reflects not only experimental barriers but also a deeper conceptual challenge: the chromatin regulators involved may themselves be species-specific. Histone variants, which replace canonical histones to modulate chromatin function, are emerging as key regulators of cell type– and species–specific developmental programs. Here, we identify a rare histone variant as a critical regulator of blastocyst formation and trophoblast lineage development in humans and bovine embryos, but not in rodents. Using an integrated approach spanning in vivo human embryos, in vitro human blastoids, in vivo bovine embryogenesis and trophoblast stem cell cultures, we show that this variant localizes to ribosomal protein gene and trophoblast gene loci and physically associates with RNA polymerases I and II, RNA biogenesis factors, as well as nucleolar regulators. Functional assays reveal the unique sequence requirement that is necessary to maintain ribosome biogenesis and trophoblast stem cell growth. Together, these findings uncover a chromatin-based mechanism that coordinates ribosomal output with lineage-specific transcription, linking histone variant function to species-specific features of developmental programs.