# Molecular understanding of maternal humoral responses to pregnancy

> **NIH NIH K99** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2024 · $123,309

## Abstract

PROJECT SUMMARY
Complications from preterm birth are the leading causes of global mortality in children under the age of five.
The failure to mount appropriately-timed maternal-fetal immune tolerance is associated with preterm delivery.
However, our current understanding of the humoral immune system in this process has been limited to a
handful of examples of pathogenic antibodies that occur with pregnancy complications in humans. To fill this
knowledge gap, it is essential to obtain a comprehensive portrait of autoimmune repertoire dynamics during
normal and complicated pregnancies. The long-term goal of this work is to leverage serological autoantibody
profiles for development of non-invasive predictors for preterm delivery and identification of key targets for
preventative immunomodulatory therapeutics. In Aim 1, Dr. Rackaityte will chronicle the autoimmune changes
across the time course of pregnancy using phage display immunoprecipitation and sequencing to generate
machine learning models predictive of gestational age. Completed during the K99 phase, this high-resolution
timeline of autoreactivity during pregnancy will build the foundation for understanding the roles, both protective
and pathogenic, of these critical humoral immune adaptations. In Aim 2, Dr. Rackaityte will dissect antibody-
antigen interactions specific to preterm pregnancy to discover contact points that lead to functional inhibition of
the targeted protein. In the K99 phase, a suite of patient-informed recombinant antibodies will be generated
through an evolution-driven antibody phage display system, and these will be tested in the R00 phase for their
ability to inhibit target protein function. This will provide the framework for future studies to interfere with
antibody-antigen interactions to prevent preterm delivery. In Aim 3, Dr. Rackaityte will develop murine models
of inflammation during pregnancy that will be employed to determine the in vivo consequences of maternal
autoantibodies on pregnancy outcome. This will deliver a validated model for interrogating the in vivo role of
autoantibodies that lead to labor progression, a unique opportunity to mechanistically dissect observations
made in humans for targeted therapeutic development. Dr. Rackaityte’s goal is to develop an independent
research program in translational reproductive immunology, which is highly complementary to the mission of
UCSF geared towards facilitating direct interactions between basic scientists and clinicians. To accomplish her
goals, Dr. Rackaitye will receive guidance from her scientific advisory committee and her primary mentor, Dr.
Joseph DeRisi. To complete her training and build a foundation of skills for her independent laboratory, she will
develop expertise in recombinant antibody generation (with Dr. Charles Craik), mouse model development
(with Drs. Tippi MacKenzie and Mark Anderson), and clinical metadata analysis of reproductive disorders (with
Dr. Marcelle Cedars). She will attend U...

## Key facts

- **NIH application ID:** 10865332
- **Project number:** 1K99AI182451-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Elze Rackaityte
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $123,309
- **Award type:** 1
- **Project period:** 2024-06-07 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10865332

## Citation

> US National Institutes of Health, RePORTER application 10865332, Molecular understanding of maternal humoral responses to pregnancy (1K99AI182451-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10865332. Licensed CC0.

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