# Evaluating the role of human cervical smooth muscle cells in normal and premature cervical remodeling

> **NIH NIH K08** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $167,724

## Abstract

ABSTRACT:
 Spontaneous preterm birth (sPTB) remains a significant obstetric dilemma with enormous costs to U.S.
healthcare. The etiology of sPTB varies, but the final common pathway involves premature cervical remodeling
(PCR), shortening and dilation. Despite the importance of this health issue, the pathophysiology of normal and
PCR in humans is not well understood. For instance, the role of cervical smooth muscle cells (CSMCs) in
cervical remodeling remains unknown. Over the last five years, under the guidance of my outstanding
mentors, I have engaged in studies of cervical remodeling and helped to establish the Collaborative Cervix
Research Group (CCRG) at Columbia University. The goal of the CCRG is to tackle the complex problem of
PCR from a truly multidisciplinary approach. My initial work established that CSMCs at the internal os are
circumferentially oriented (similar to a “sphincter”) and cervical tissue from the internal os contracts in response
to oxytocin. I propose that CSMCs may have two key functions: contraction and/or ECM remodeling. As
pregnancy grows, the pressure from the growing fetus applies stretch to cervix. I hypothesize that CSMC
stretch induces contraction (to maintain sphincter tone) and/or ECM remodeling. Further, I hypothesize that
women with PCR exhibit abnormal cervical stretch responses, contractile force and/or ECM remodeling. In
Aim 1, I will stretch pregnant cervical tissue biopsies and CSMCs from women with (study group) and without
PCR (controls, CTL) to establish 1) if stretch induces cervical contractility, 2) if cervices and CSMCs from
women with PCR exhibit aberrant contractility and 3) potential contractile mechanisms which may explain the
contractility defect. In Aim 2, I will investigate if cervical tissue and CSMCs from women with PCR 1) exhibit
abnormal stretch responses resulting in increased MMP activation, collagen turnover/ECM remodeling
compared to CTLs and 2) if inflammation further enhances this stretch-induced MMP activation/ECM
remodeling. In Aim 3, I will evaluate if stretch-induced molecular phenotypic changes exist at the transcriptome
level in CSMC from women with PCR vs CTL with particular attention to contractility and ECM remodeling
pathways. Toward this goal, I have been collecting tissue from pregnant women with a history of PCR and
from gestational age-matched CTLs using IRB approved protocols. If women with PCR have 1) CSMCs that
cannot contract and maintain “sphincter-like” tone in response to stretch and/or 2) exhibit abnormal ECM
remodeling responses to stretch resulting in a mechanically weaker cervix, this may explain why the cervix
ultimately fails leading to sPTB. With the guidance of my mentors and CCRG team, this award will allow me to
expand my experimental knowledge base and investigational skills so I may achieve my ultimate goal of
becoming a successful and independent clinician scientist whose focus is to prevent PCR and PTB.

## Key facts

- **NIH application ID:** 9975869
- **Project number:** 5K08HD088758-05
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** Joy-Sarah Vink
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $167,724
- **Award type:** 5
- **Project period:** 2016-08-01 → 2021-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975869

## Citation

> US National Institutes of Health, RePORTER application 9975869, Evaluating the role of human cervical smooth muscle cells in normal and premature cervical remodeling (5K08HD088758-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9975869. Licensed CC0.

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