# Identifying placental injury pathways in women of African ancestry with severe preeclampsia

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $434,500

## Abstract

Summary/Abstract
Women of African ancestry are 3 to 5-times more likely to die of preeclampsia, a pregnancy-induced
hypertensive disorder, or suffer bad outcomes like stroke, pulmonary edema and heart failure, than women of
Asian or European ancestries. The placenta plays a central role in the pathology of preeclampsia, as delivery
is often curative. However, how the placenta contributes to worse outcomes in women of African ancestry, and
which specific placental injury pathways may be targeted for therapy, are not well studied. An exciting evolution
in elucidating the underlying pathophysiology of preeclampsia is the concept that the disease has multiple
etiologies that manifest differently in the placenta. Therefore, the aim of this study is to identify the specific
placental cellular and molecular injury pathways that may account for the disproportionately worse outcomes in
women of African ancestry in comparison to women of European and Asian ancestries. The ultimate goal is to
identify pathways of placental injury that can be targeted to improve pregnancy outcomes in women of African
ancestry. The central hypothesis is that immunologic processes, including non-permissive HLA
mismatches and upregulation of genes associated with immune activation underlie the
pathophysiology of severe preeclampsia in women of African ancestry compared to women of Asian
and European ancestry. This hypothesis will be tested in two specific aims: 1. Identify the region and cell-
specific localization of genes and pathways that are differentially expressed/altered in placentas of women with
severe preeclampsia versus normotensive women of African ancestry, in contrast to women of Asian and
European ancestries, using digital spatial transcriptomics, and evaluate how the placental immune cell milieu
changes in these patient populations using immunohistochemistry. 2. Evaluate the role of maternal-fetal HLA
mismatches and altered placental expression of HLA molecules in the pathophysiology of severe preeclampsia
in women of African ancestry versus women of Asian and European ancestries using comprehensive HLA
genotyping, HLA functional prediction analysis and immunohistochemistry. The proposed research is
conceptually innovative because it will address the pathophysiology of severe preeclampsia in women of
African ancestry (compared to women of Asian and European ancestries) from the context of differential
placental manifestations of the disease. It is technically innovative because it will integrate both RNA profiling
(via RNA sequencing and digital spatial transcriptomics) and protein expression (via immunohistochemistry) to
identify placental cellular processes, genes, and pathways that will potentially be therapeutic targets to
modulate the worse outcomes of severe preeclampsia in women of African ancestry. Furthermore, it is
innovative in its depth because it will include comprehensive HLA genotyping, HLA functional prediction
analysis and HLA immunohistochemist...

## Key facts

- **NIH application ID:** 10742342
- **Project number:** 1R21HD110611-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Omonigho Augustina Aisagbonhi
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $434,500
- **Award type:** 1
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10742342

## Citation

> US National Institutes of Health, RePORTER application 10742342, Identifying placental injury pathways in women of African ancestry with severe preeclampsia (1R21HD110611-01A1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10742342. Licensed CC0.

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