# Dissecting the role of vascular endothelial BMP9 signaling in lung transplantation

> **NIH NIH F31** · NORTHWESTERN UNIVERSITY · 2024 · $44,187

## Abstract

Abstract
Primary Graft Dysfunction (PGD) has a 30% prevalence post lung transplantation (LTx) and is the leading cause
of morbidity and mortality. The mechanisms that contribute to PGD are complex. However, the process of
ischemia reperfusion injury (IRI) and degree of injury to the lung microvasculature are known contributors to
PGD development. Despite significantly worsening short and long-term survival outcomes, there are currently
no FDA approved therapies for PGD. Injury to the microvascular beds leads to dysfunctional and activated
vascular endothelial cells which are pro-inflammatory, lack barrier integrity, and improperly regulate immune cell
extravasation [17,18]. Bone morphogenetic protein 9 (BMP9) is a critical lung microvascular homeostasis and
quiescent factor. Loss of BMP9 signaling has been shown to promote lung pathology in a number of lung acute
and chronic diseases. Whether BMP signaling plays a role in the acute lung injury seen in LTx PGD has not
been previously investigated. Here we present novel preliminary data showing that BMP signaling is
significantly downregulated as a consequence of IRI, using in vitro and in vivo models of LTx. We further
demonstrate that exogenous augmentation of circulating BMP9 significantly reduces post-LTx IRI. Based on
these novel data, the important role that BMP signaling plays in endothelial homeostasis, and protective effects
that exogenous BMP9 therapy yields in other experimental lung injuries, we hypothesize that impaired
microvascular BMP signaling promotes lung endothelial injury and the development of primary graft
dysfunction. Our overarching goal is to mechanistically dissect and define how BMP microvascular homeostasis
pathway is impacted by lung transplantation and develop pathway-specific novel pharmacotherapeutic
interventions. SA. 1. Determine the mechanisms by which BMP signaling contributes to primary graft
dysfunction and SA. 2. Explore the therapeutic potential of modulating the BMP9 signaling axis as a
means to improve LTx outcomes. We hypothesize that augmentation of BMPR2 signaling will promote
protection from IRI and the development of PGD. On completion of these studies, our short-term goal will
provide novel insights into the role of the BMP signaling pathway in endothelial injury and LTx. These proposed
studies will further support our long-term goal to provide important information that could contribute to the
establishment of tailored BMP signaling pathway interventions that could serve as novel pharmacotherapeutic
strategy to improve early lung transplant outcomes. Based on the literature, these therapies may translate to
significantly improved long-term allograft survival.

## Key facts

- **NIH application ID:** 10996899
- **Project number:** 1F31HL176117-01
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Blake Gill
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $44,187
- **Award type:** 1
- **Project period:** 2025-02-06 → 2027-02-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10996899

## Citation

> US National Institutes of Health, RePORTER application 10996899, Dissecting the role of vascular endothelial BMP9 signaling in lung transplantation (1F31HL176117-01). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/10996899. Licensed CC0.

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