Humphrey Yao, Ph.D.
Reproductive & Developmental Biology Laboratory / Reproductive Developmental Biology Group
C458A Rall Building
111 T W Alexander Dr
Research Triangle Park, NC 27709
Compelling animal evidence and human epidemiological data have revealed that impairment of fetal organ development has profound consequences on adult health. The concept of "fetal origins of adult diseases" also applies to the reproductive systems where formation of most reproductive organs is completed before birth. Defects in reproductive organ formation manifest as disorders of sex development. However, minor abnormalities are often left undetected and become a potential cause of fertility problems and neoplasia when the affected individual reaches adulthood.
The Reproductive Developmental Biology Group uses organogenesis of the gonads and reproductive tracts as a model to understand the basic process of organ formation and the potential implication of the impacts of endocrine disruptor exposure to reproductive organ formation in fetuses and fertility in adulthood. Reproductive organs are one of the few organs that exhibit dramatic sex-specific pattern of dimorphic development. This unique pattern of development provides a model to understand not only the mechanism of sex determination, but also how progenitor cells make the decision to differentiate into tissue-specific cell types, the fundamental concept of embryology.
Major Areas of Research
- Understand how different somatic cell lineages (Sertoli and Leydig cells in the testis and granulose and theca cells in the ovary) are formed in the fetal testis and ovary, respectively
- Define the cellular processes that lead to sexually dimorphic establishment of the reproductive tracts
- Investigate the effects of in utero exposure to endocrine disruptors on organogenesis of reproductive organs and lingering impacts on fertility in adulthood.
- Define the linage progression roadmap of somatic cells in the gonads by single cell sequencing (Drop-seq and combinatorial indexing technique).
- Identify novel players in gonadal organogenesis using conditional genetic approaches, ChIP-seq, ATAC-seq, and RNA-seq.
- Investigate the molecular interaction between COUP-TFII, androgen receptors, and other transcription factors in maintaining the male reproductive tract.
- Examine the impact of in utero exposure to endocrine disrupting agents (arsenic and phthalates) on reproductive organ development and fertility.
Dr. Yao received his doctoral degree at the University of Illinois in Urbana-Champaign in 1999 and then completed his postdoctoral training at Duke University Medical Center in 2002. He became Assistant Professor in the Department of Comparative Biosciences at University of Illinois in Urbana-Champaign in 2003 and received tenure in 2009. Dr. Yao moved to NIEHS in 2010 and was promoted to Senior Investigator in 2018. Dr. Yao was the recipient of the Basal O'Connor Starter Research Award from March of Dimes Birth Defect Foundation, Pfizer Research Award, New Investigator Award for the Society for the Study of Reproduction, and Young Andrologist Award from the American Society of Andrology. He was also elected as the Chair for the 2018 Gordon Research Conference on Mammalian Reproduction.
Zhao F, Franco HL, Rodriguez KF, Brown PR, Tsai MJ, Tsai SY, Yao HH. Elimination of the male reproductive tract in the female embryo is promoted by COUP-TFII in mice. Science. 2017;357(6352):717-720.
Nicol B, Grimm SA, Chalmel F, Lecluze E, Pannetier M, Pailhoux E, Dupin-De-Beyssat E, Guiguen Y, Capel B, Yao HH. RUNX1 maintains the identity of the fetal ovary through an interplay with FOXL2. Nat Commun. 2019;10(1):5116.
Rodriguez KF, Ungewitter EK, Crespo-Mejias Y, Liu C, Nicol B, Kissling GE, Yao HH. Effects of in Utero Exposure to Arsenic during the Second Half of Gestation on Reproductive End Points and Metabolic Parameters in Female CD-1 Mice. Environ Health Perspect. 2016;124(3):336-43.
Nicol B, Grimm SA, Gruzdev A, Scott GJ, Ray MK, Yao HH. Genome-wide identification of FOXL2 binding and characterization of FOXL2 feminizing action in the fetal gonads. Hum Mol Genet. 2018;27(24):4273-4287.
Liu C, Peng J, Matzuk MM, Yao HH. Lineage specification of ovarian theca cells requires multicellular interactions via oocyte and granulosa cells. Nat Commun. 2015;6:6934.
Related Scientific Focus Areas
Genetics and Genomics
This page was last updated on September 4th, 2018