Zachary Smith, Yale Medical School

Zachary Smith, Yale Medical School

Butler Seminar Series

Event Date/Location

October 5, 2022 - 12:00 pm to 1:00 pm
Thomas Laboratory 003


  • Zack Smith Photo

    Zachary Smith, Ph.D.

    Assistant Professor of Genetics
    Yale School of Medicine

    Zachary Smith received his B.S. in Biology from M.I.T. in 2008. Inspired by the recent works of Takahashi and Yamanaka and by the first genome-wide “epigenomes” from the Broad Institute, he joined Dr. Alex Meissner’s new lab at Harvard University’s Department of Stem Cell and Regenerative Biology as its first employee. During his time as a Research Assistant, Zachary published research on direct reprogramming of somatic cells to pluripotency, including early morphological changes by live imaging and chromatin dynamics by Chromatin Immunoprecipitation followed by high throughput sequencing (ChIP-seq). He also optimized emerging genome-scale technologies to study DNA methylation in precious samples and used these to understand its global dynamics during early mouse and human development. After matriculating into Harvard’s Molecules, Cells and Organisms (MCO) program in 2013, Zachary continued applying cutting edge technologies to understand global changes in genome regulation as they contribute to mammalian development, including new strategies to study the roles of chromatin regulators during implantation and gastrulation. Furthermore, he collaborated with Jonathan Weissman’s lab at UCSF to produce a novel Cas9-based molecular recorder, which can recover the historical relationships between single cells and used to construct comprehensive lineage hierarchies. These and other technologies offer new approaches for quantitative ontogeny, the population-level coordination of progenitor fields as they commit to form complex structures. Zachary received his Ph.D. in 2019 and joined the Yale Stem Cell Center and Department of Genetics as an Assistant Professor in September, 2020.


Epigenetic landscapes in early mammalian development

Epigenetic modifications act in combination to provide essential developmental and regulatory codes. Although maintained as predominantly static and robust patterns within healthy adult tissues, these modifications are globally reprogrammed at fertilization and must be systematically redeployed to support embryonic differentiation and growth.  I will present our lab’s ongoing efforts to understand distinct forms of genome regulation as they emerge during this highly dynamic period.  In particular, we hope to identify molecular pathways that distinguish the fetal epigenome from a second, seemingly more dynamic program specific to the extraembryonic placenta and yolk sac.  Further insights from patient data suggest that this alternative regulatory mechanism may also be coopted as a general feature of malignant transformation in cancer.  Finally, I will highlight our work to pinpoint how epigenetic complexes themselves guide the differentiating embryo through the highly coordinated processes of gastrulation and early organogenesis.  We hope to ultimately integrate our observations from developmental and genome biology as a means of uncovering the environmental and epigenetic origins of complex congenital disorders.


Free and open to the university community and the public.


Michelle Chan, Department of Molecular Biology