The UCSF NCTRI is dedicated to stimulating, funding, and guiding promising and innovative projects related to the immunological, epigenetic, and developmental determinants of fertility and infertility - from gametogenesis to embryogenesis to implantation and placentation. This internal pilot project program funds innovative proposals related to this research area from UCSF researchers in a variety of disciplines and perspectives. We have a yearly request for applications; all faculty ranks, new/early career investigators, professional research series, research specialist series, senior postdoctoral fellows and senior clinical fellows at UCSF are eligible to apply. Individuals in non-faculty track positions at UCSF are eligible with a faculty member as a mentor and Co-PI. Race, gender, or other protected categories or proxies for protected categories are not used as selection criteria.

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2025-2026 Characterization of the human maternal-fetal interface transcriptome at the single cell level in mid-gestation

Alicia Bárcena, PhD

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The overall objective of this pilot project is to learn more about the normal transcriptome and distribution of populations of immune and non-immune cells in pregnant (therefore, fertile) women at the maternal-fetal interface at mid-gestation. Investigating the transcriptome in the fetal membranes (which account for more than 70% of the maternal-fetal interface) during mid-gestation will expand our knowledge on how the immune and non-immune cell populations interact in pregnancy. This information might lead to the identification of regulatory mechanisms, pathways, cell types and immune functions that are critical to maintain pregnancy in a regulated state. The approach is to perform single cells RNA sequencing and downstream analyses of gene expression in several samples of sorted CD45+ (containing immune cells) and CD45- cell populations isolated from the smooth chorion (fetal) and decidua (maternal). These data might provide new insights into the immune dysregulation observed in pathologies associated with infertility, such as endometriosis and PCOS, and could lead to discover novel targets for diagnosis and treatments for female infertility. 

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2024-2025 Investigating Putative Embryonic Lethal Variants in Human Blastoids

Michelle Halstead, PhD

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Recurrent pregnancy loss (RPL) affects up to 5% of couples and remains a significant clinical and emotional burden. While chromosomal abnormalities account for about half of early pregnancy losses, the genetic basis of many euploid miscarriages remains poorly understood. Ongoing efforts at UCSF are using whole genome sequencing (WGS) to identify candidate lethal variants associated with miscarriage, but validating their impact on human development is challenging. This project aims to establish human stem cell-derived embryo-like structures, or “embryoids,” as a model system to study the functional consequences of lethal variants. Embryoids mimic key stages of early human development, including blastocyst formation and gastrulation, providing an ethical and human-specific platform for investigating how candidate variants impair developmental milestones. By introducing RPL-associated variants into stem cells and evaluating their ability to form embryoids, this study seeks to uncover critical insights into the genetic mechanisms underlying RPL.