# Understanding fibrin degradation by matrix metalloprotease-1 at the single molecule level

> **NIH NIH R15** · COLORADO SCHOOL OF MINES · 2022 · $50,141

## Abstract

Project Summary/Abstract
Every year, ~900,000 Americans are diagnosed with complications from clot formation leading to ~300,000
deaths and ~$28 billion annual cost. The number of adults with clot-related complications are estimated to reach
~1.82 million by 2050. Blood clots form through the coagulation cascade and are part of the natural response to
injury and cut, preventing loss of blood from severed blood vessels. However, the life-saving process of clot
formation can become life-threatening if a blood vessel is blocked due to a clot. Indeed, clot-related pathologies
including heart attack, stroke, and pulmonary embolism account for ~50% of all hospital deaths. Reperfusion,
the act of restoring blood flow, with tissue plasminogen activator (tPA) is the gold standard treatment for ischemic
stroke. Adverse side effects and cost of tPA motivate alternative approaches to treat clots. A major component
of blood clots is crosslinked fibrin. Water-soluble fibrin monomers assemble into water-insoluble fibrin polymer,
which makes them difficult to study using common biochemical assays. Human matrix metalloproteases
(MMPs) present in blood have fibrinolytic activity and are therefore potentially alternative targets in
blood clot management. MMPs are a family of 25 enzymes and are implicated in the majority of the top ten
causes of death. MMP1 is the best studied member of the MMP family with a crystal structure available and
details of its interaction with collagen known. We have strong evidence for fibrinolytic activity of MMP1, which is
modulated by antibiotics and MMP9, another important MMP-family member that is upregulated in many disease.
We propose to define the mechanism of fibrin degradation at the single molecule with synergistic applications of
ensemble assays and molecular dynamics simulations.

## Key facts

- **NIH application ID:** 10624524
- **Project number:** 3R15GM137295-01S1
- **Recipient organization:** COLORADO SCHOOL OF MINES
- **Principal Investigator:** JUDITH KLEIN
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $50,141
- **Award type:** 3
- **Project period:** 2020-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10624524

## Citation

> US National Institutes of Health, RePORTER application 10624524, Understanding fibrin degradation by matrix metalloprotease-1 at the single molecule level (3R15GM137295-01S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10624524. Licensed CC0.

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