# Discovery of Novel Therapeutics for Inflammation Induced Preterm Birth

> **NIH NIH K99** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2022 · $107,695

## Abstract

PROJECT SUMMARY
 In this K99/R00 Pathway to Independence application, the candidate proposes a structured, rigorous and
detailed training plan to build expertise in ex vivo gestational tissue modeling and preterm birth physiology along
with continued education in the latest approaches for drug discovery. This training plan will be supported through
hands-on-training, coursework, workshops, training in the responsible conduct of research, seminars and
conferences. The candidate also proposes to gain experience in operating an independent research lab through
grant writing workshops, networking and mentorship from a multidisciplinary advisory committee with expertise
in obstetrics, reproductive sciences, neonatology, infectious disease and chemical biology/pharmacology, whom
have long track records in training future independent researchers. The work in K99 phase will be completed at
Vanderbilt University Medical Center, which has a plethora of resources and expertise available that perfectly
aligned with the PI’s needs. The candidate`s primary goal is to establish a successful, independent research
program that tests translational interventions aimed at management of infection-induced preterm labor (III-PTL).
 Preterm birth, defined as delivery before 37 weeks of gestation, is the leading worldwide cause of infant
morbidity and mortality. Intrauterine infection and/or inflammation is a major trigger of early labor leading to
preterm birth and fetal inflammation causing adverse neonatal outcomes. Unfortunately, there is a critical lack
of therapeutics for the management of early labor that occurs as the result of infection/inflammation during
pregnancy. Studies involved in the K99 and R00 phases of this proposal encompass novel approaches to identify
effective therapeutic agents to manage III-PTL without adverse effects. Recent transcriptomic studies on
gestational membranes have identified gene targets implicated in III-PTL and we have determined which of these
genes are part of the druggable genome and could be explored for therapeutic regulation of III-PTL. In Aim 1
(K99) we will optimize a high-throughput screening (HTS) assay to measure changes in proinflammatory
cytokines released from pathogen-associated molecular patterns (PAMP)-induced gestational membrane (GM)
explants in 96-well format. We will utilize this HTS assay to screen a customized library of small-molecules that
target the druggable transcriptome associated with III-PTL. We will perform a series of secondary screens to
prioritize hit-molecules into leads. In Aim 2 (R00 phase), we will utilize a high-throughput combination screen to
identify combination therapeutics with synergistic effects. In Aim 3 (R00 phase), mouse models of III-PTL will be
used to confirm the in vivo ability of our lead-single or synergistic combinations to manage PTL and protect
against fetal inflammation. The training plan and outstanding mentoring committee will ensure the success of
the project and suppo...

## Key facts

- **NIH application ID:** 10429552
- **Project number:** 1K99HD108420-01
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Shajila Siricilla
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $107,695
- **Award type:** 1
- **Project period:** 2022-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10429552

## Citation

> US National Institutes of Health, RePORTER application 10429552, Discovery of Novel Therapeutics for Inflammation Induced Preterm Birth (1K99HD108420-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10429552. Licensed CC0.

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