Comprehensive, high-resolution epigenomic profiling of DNA methylation dynamics across primate germ cell development. Uncovered primate-specific timing, target genomic regions, and regulatory mechanisms of de novo DNA methylation, offering pivotal insights into human germline biology and fertility.

Demonstrated that Wnt4 signaling coordinates cell cycle exit and the epigenetic remodeling necessary for meiotic entry in female germ cells. Disruption of Wnt4 alters DNMT expression, persistent H3K27me3 accumulation, and the reciprocal regulation of DNA methylation and histone acetylation at key meiotic loci such as Stra8 and Sycp3.

Demonstrated that abnormal activation of H3K27me3 demethylases KDM6A/B triggers a localized loss of repressive H3K27me3 marks in cryptorchid spermatogonial stem cells, aberrantly derepressing developmental and pro-apoptotic genes and leading to stem cell degeneration.

Comprehensive spatio-temporal expression profiling of BMP signaling modifiers Smoc1 and Smoc2 throughout postnatal to adult testis development, identifying their distinct compartmentalization across somatic niche and germline lineages.

Demonstrated that non-canonical bivalent chromatin pre-programs Wfdc15a in spermatogonial stem cells, which acts downstream in late spermatids to control serine protease activity and testicular immune homeostasis, ensuring male fertility.

Uncovered the vital niche role of Sertoli-derived brain-derived neurotrophic factor (BDNF) and its TrkB receptor in providing indispensable background survival signals and differentiation balance in mammalian spermatogonia.

Demonstrated that oxygen concentration during in vitro follicle culture substantially alters de novo DNA methylation and transcriptomic fidelity in developing oocytes, establishing critical quality benchmarks for assisted reproduction.

Revealed that maintenance DNA methylation via Np95/Uhrf1 in pre-meiotic germ cells directly facilitates homologous chromosome pairing, establishing an essential epigenetic requirement for successful meiotic progression.

Identified Tsga8 as an essential testis-specific structural gene required for sperm head shaping, flagellar assembly, and male fertility, establishing its role in mammalian spermiogenesis.

Generated WFDC2 (HE4) knockout mice, discovering that deficiency in this protease inhibitor leads to severe alveolar collapse, unregulated inflammation, and lethal neonatal respiratory failure.

Revealed that histone methyltransferase Kmt2b deposits monovalent and bivalent H3K4me3 marks at germline and developmental gene promoters in spermatogonial stem cells, pre-programming future lineage fidelity.

Demonstrated that the RNA-binding protein Nanos2 establishes a post-transcriptional buffering network that preserves stemness and prevents precocious differentiation in mouse spermatogonial stem cells.

First report identifying an epigenetic checkpoint controlling the transition from a homogenous stem cell pool to progenitor states in mouse male germ cells, mediated by dynamic DNA methylation and histone changes.

Demonstrated that piRNAs and long noncoding RNAs cooperate to direct target-specific de novo DNA methylation at imprinted loci (Rasgrf1) in the developing male germline.