# Selective targeting of matrix metalloproteinases for developing preterm labor therapeutics

> **NIH NIH R21** · UNIVERSITY OF NEVADA RENO · 2022 · $211,204

## Abstract

PROJECT SUMMARY/ABSTRACT
We have shown that specific members of the matrix metalloproteinase family (MMP-2 and MMP-9) are
overexpressed in preterm laboring myometrium and that these enzymes exacerbate contractile responses in
human uterine smooth muscle. Therefore, MMP-2/9 may serve as therapeutic targets to block preterm labor.
Tissue inhibitors of metalloproteinases (TIMPs) are endogenous MMP inhibitors with subnanomolar affinity.
Considering multifaceted role of MMPs in cellular function, we aim to target specific MMPs (MMP-2/9),
responsible for uterine contraction in patients with preterm labor, with high selectivity while avoiding
interactions with other beneficial MMPs. Our central hypothesis is that selective TIMP protein-based
therapeutics can be developed to promote uterine quiescence. We will use protein engineering techniques
such as directed evolution to produce tocolytic drug candidates based on TIMP protein scaffold to treat preterm
labor. In Aim 1, we will use directed evolution and yeast surface display to engineer TIMP-based protein
scaffolds to improve binding selectivity toward MMP-2/9. In Aim 2, we will evaluate the ability of wild-type and
engineered TIMPs to reduce contractions in human uterine tissue. These data are expected to be significant
because they will provide the foundation for candidate drug testing in preclinical in vivo models of preterm
labor.

## Key facts

- **NIH application ID:** 10509786
- **Project number:** 1R21HD109743-01
- **Recipient organization:** UNIVERSITY OF NEVADA RENO
- **Principal Investigator:** Maryam Raeeszadeh Sarmazdeh
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $211,204
- **Award type:** 1
- **Project period:** 2023-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10509786

## Citation

> US National Institutes of Health, RePORTER application 10509786, Selective targeting of matrix metalloproteinases for developing preterm labor therapeutics (1R21HD109743-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10509786. Licensed CC0.

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