# Biomarkers of Chlamydial Susceptibility and Disease

> **NIH NIH U19** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $117,278

## Abstract

In a subset of Chlamydia trachomatis-infected women, the infection escapes immune control and ascends to the
upper reproductive tract. There is a fundamental gap in understanding how pathways activated by chlamydial
infection lead to immune pathology and reproductive morbidity in women. Its continued existence is a significant
barrier to identification of biomarkers to diagnose or predict risk for reproductive sequelae after exposure. The
long-term goal of this program is to develop vaccines that reduce transmission and prevent reproductive tract
sequelae after exposure to C. trachomatis. The overall objective of this proposal is to identify biomarkers of
asymptomatic ascending infection and endometritis in women and genetic biomarkers of susceptibility/risk for
disease. The central hypothesis is that protective and immunopathologic responses elicited in response to STI
associate with characteristic transcriptional signatures and genetic variance. The rationale for this project is that
identifying biomarkers of susceptibility to ascending infection and risk for subsequent immune pathology will
accelerate rational vaccine design and testing by (i) identifying individuals most likely to benefit from
immunization, to facilitate appropriately powered studies, (ii) enabling balanced group selection for vaccine trials,
and (iii) serving as clinical measures of vaccine efficacy. Blood-borne transcriptional profiling of women with a
spectrum of chlamydial genital tract infection revealed specific inflammatory pathways associated with disease
and enabled definition of a biomarker panel that diagnoses endometritis in asymptomatically-infected women
with high chlamydial burden. Guided by strong preliminary data, the following three specific aims will test the
hypothesis: 1) Determine candidate biomarkers positively- or negatively associated with ascending chlamydial
infection in asymptomatic women; 2) Identify genetic biomarkers of susceptibility to ascending chlamydial
infection and risk for subsequent reproductive sequelae; and 3) Identify disease-causing pathways and their key
regulators engaged during ascending chlamydial infection, using causal network analysis. The first aim will profile
cervical inflammatory responses from women with local infection or upper tract involvement in a new cohort of
highly-exposed women (TRAC2, Core B). Pathogen load, co-infection, cervicovaginal microbiome and hormonal
contraceptives will be assessed as confounders or additional biomarkers. The remaining aims will focus on
integrating genotype, gene expression and disease phenotypes from TRAC2 and previously-profiled cohorts via
expression quantitative trait locus (eQTL) mapping and causal mediation test, and on identification of disease-
causal genes, using graphical models. The research proposed is innovative, in our opinion, because it will
implement a comprehensive, non-biased approach to the identification of molecular biomarkers in a highly
disease-relevant clinica...

## Key facts

- **NIH application ID:** 10149924
- **Project number:** 5U19AI144181-03
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** CATHERINE MARY O'CONNELL
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $117,278
- **Award type:** 5
- **Project period:** 2019-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10149924

## Citation

> US National Institutes of Health, RePORTER application 10149924, Biomarkers of Chlamydial Susceptibility and Disease (5U19AI144181-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10149924. Licensed CC0.

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