# Role and regulation of vascular permeability in pulmonary fibrosis

> **NIH NIH K08** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $172,800

## Abstract

Project Summary
Candidate: Rachel Knipe, MD is a physician in the Division of Pulmonary and Critical Care at
Massachusetts General Hospital (MGH) and an Instructor of Medicine at Harvard Medical
School (HMS). She has developed expertise in cell and molecular biology and murine modeling
of pulmonary fibrosis, focusing on the role of ROCK, S1P1 and the actin cytoskeleton in
fibrogenesis. This K08 application aims to understand the role of vascular permeability in the
development of pulmonary fibrosis, studying two opposing regulators of permeability, ROCK
and S1P1. Her short-term goals are to obtain training in endothelial biology, animal modeling of
human lung disease, micro-engineered culture systems, and translational research. Her long
term goal is to lead a translational research program on vascular permeability and pulmonary
fibrosis. The experiments, training, and mentoring plan outlined in this proposal will successfully
position Dr. Knipe for her first R01 and an independent career as a physician-scientist.
Mentorship, Training Activities and Environment: Dr. Knipe will perform the work outlined in
this proposal in the Division of Pulmonary and Critical Care Medicine under the mentorship of
Drs. Benjamin Medoff and Andrew Luster. Drs. Medoff and Luster both have extensive
experience in mouse modeling of lung disease and translational research and excellent records
of mentoring. Drs. James Liao, Timothy Hla, Christopher Chen and Barry Shea will serve on Dr.
Knipe's advisory committee and provide expertise in ROCK and S1P1 signaling, mouse
modeling of lung disease, cellular biology utilizing advanced micro-engineered culture systems
and translational research. Dr. Knipe will complete courses in endothelial biology, mouse
modeling of human lung disease, tissue engineering, and translational research through
Harvard Medical School and Harvard University.
Research: Idiopathic Pulmonary Fibrosis (IPF) is a progressive scarring lung disease that very
often leads to respiratory failure. There remains a large unmet need for effective therapies. IPF
is thought to be driven by dysfunctional wound healing responses to repetitive tissue injury.
Increased vascular permeability is a cardinal wound healing response, which in the lung allows
plasma proteins to leak from the pulmonary vasculature into the airspaces. Increased
permeability has been shown in the lungs of IPF patients, and predicts mortality. We propose
that restoring endothelial barrier function after lung injury, either by inhibiting endothelial cell
ROCK activation or augmenting endothelial cell S1P1 activation, could provide a novel and
specific therapeutic strategy to attenuate the development of pulmonary fibrosis.

## Key facts

- **NIH application ID:** 10457937
- **Project number:** 5K08HL140175-05
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Rachel S Knipe
- **Activity code:** K08 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $172,800
- **Award type:** 5
- **Project period:** 2018-08-05 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10457937

## Citation

> US National Institutes of Health, RePORTER application 10457937, Role and regulation of vascular permeability in pulmonary fibrosis (5K08HL140175-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10457937. Licensed CC0.

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