John C. Schimenti

This study models human MLH1 and MLH3 variants in mice, revealing MutLγ's roles in meiotic DNA repair and ovarian reserve maintenance through multiple mechanisms.

This study shows that replication stress from MCM2-7 mutations impairs placenta development in mice by reducing junctional zone proliferation and stemness, leading to poor embryo viability.

This paper develops a scalable method to generate PGC-like cells and uses it to identify epigenetic factors affecting germline development.

This study investigates how mouse embryonic stem cells respond to DNA replication stress, finding they survive via ATR- and CHK1-dependent mechanisms but lack a strong G2/M checkpoint and repair DNA crosslinks in S phase.

This study uses combinatorial CRISPR mutagenesis in organoids to identify gene combinations driving malignant transformation, pathology, and chemosensitivity in high-grade serous ovarian carcinoma.

The paper identifies pre-ciliated tubal epithelial cells as a cancer-prone state in high-grade serous ovarian carcinoma by analyzing mouse uterine tube cell states and lineage dynamics.

The paper identifies post-transcriptional regulators in early human small intestinal development using multi-omic analyses and presents a web tool for exploring miRNA regulation.

The paper develops MN-seq to sequence DNA in micronuclei, revealing factors contributing to chromosomal instability and introducing scMN-seq for single-cell analysis.

The paper evaluates the functional impact of missense variants in human reproductive genes using mouse models and finds that many predicted pathogenic variants do not cause detectable phenotypes.

The paper identifies MLH1/3 variants in mice that cause reproductive defects, including subfertility and increased pregnancy loss due to meiotic abnormalities.

This paper compares CRISPR-mediated HDR and PE2 systems in mice to show PE2's higher fidelity in editing a TFBS, leading to more effective tissue-specific gene inactivation.

This study investigates DNA damage responses in mouse primordial germ cells, showing sex-specific differences in mutation avoidance and developmental outcomes after ionizing radiation exposure.

The paper identifies two RABL2A variants causing male infertility and ciliopathies by combining in silico predictions, protein stability assays, and mouse modeling.

This study identifies miR-375 as a key regulator of intestinal crypt homeostasis, showing its role in stem cell proliferation, tuft cell abundance, and resistance to infection and cancer.

The paper shows that CHK1/CHK2 signaling to TRP53/TAp63 eliminates oocytes with unrepaired meiotic DSBs or asynaptic chromosomes.

The paper identifies a predicted deleterious SNP in the MND1 gene present in East Asians but shows it does not affect mouse fertility.

The paper models a human SPO11 variant in mice, showing it disrupts meiotic recombination, leading to reduced sperm and oocytes and fertility issues.

The paper shows female mouse embryos are more susceptible to embryonic lethality from genomic instability-induced inflammation, which is mitigated by testosterone or anti-inflammatory drugs.

This study shows that CDK2 kinase activity regulates male germ cell fate by controlling the balance between stem cell renewal and differentiation, with loss of function leading to infertility.

The paper creates a mouse model of a putative infertility allele, DMC1M200V, and finds it does not affect fertility in mice.

The paper shows that the CHK2-dependent checkpoint eliminates mouse oocytes with DNA damage or synapsis failure by detecting and removing those with unrepaired DSBs or unsynapsed chromosomes.

This study shows that MCMDC2 is essential for meiotic DNA break repair and homolog pairing in mice, with phenotypes similar to MSH4/5 deficiency.