Zhiyuan "ZY" Chen, PhD

I’m a reproductive biologist in the Department of Reproductive Sciences. I became interested in this topic when I studied mammalian early development as an undergraduate student. I have been fascinated by this field ever since.

I investigated genomic imprinting and loss-of-imprinting disorders during my graduate work with Dr. Rocío Melissa Rivera at the University of Missouri-Columbia. I applied low-input epigenome profiling and acute protein degradation techniques to study epigenetic reprogramming in mammalian early development for my postdoctoral training in Dr. Yi Zhang's lab at Harvard Medical School.

A new life begins at the fertilization of an egg by the sperm. After fertilization, the terminally differentiated gametes convert into a totipotent zygote. During the parental-to-zygotic transition, much of the parental epigenomes are reset except for imprinted loci. This resetting process is known as epigenetic reprogramming.

Our lab aims to understand epigenetic reprogramming by studying:

• Chromatin dynamics and functions during the parental-to-zygotic transition
• Key factors required for totipotency acquisition
• The biological significance of retrotransposon expression dynamics in early development

We implement interdisciplinary approaches to address these fundamental questions. The methods include embryo micro-manipulation, stem cell biology, (epi)genome editing, ultra-low input epigenome profiling, rapid protein degradation, high throughput genome-wide sequencing and computational techniques. Our lab aims to understand what determines totipotency, an amazing capacity that a single cell can develop into a whole animal with hundreds of cell types.

One of my significant discoveries is investigating how oocyte chromatin has a longstanding effect on embryonic development. It was previously thought that oocyte chromatin modifications are rapidly erased after fertilization. However, my colleagues and I found that a repressive histone modification, H3K27me3, can inherit from oocytes to early embryos to modulate gene expression. My work also revealed the importance of maternal H3K27me3 in regulating placental development and elucidated the crosstalk between H3K27me3 and another Polycomb mark, H2AK119ub1, in mouse early development.

I’ve been a researcher for over 12 years, and I began my work with Cincinnati Children's in 2023. I am honored to receive a National Institutes of Health (NIH) Pathway to Independence Award (K99 / R00) from the National Institute of Child Health and Human Development (2021–2026).