# Role of bone marrow cells in pathogenesis and therapy of heritable pulmonary arterial hypertension

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $634,580

## Abstract

PI: Hamid, Rizwan, MD, Ph.D.
Role of bone marrow cells in pathogenesis and therapy of heritable pulmonary arterial hypertension
PROJECT SUMMARY
The long-term objective of this project is to devise better treatment options for autosomal dominant Heritable
Pulmonary Arterial Hypertension (HPAH), a rare genetic disorder of lungs. HPAH is a lethal disorder without
effective treatment options. The predominant cause of HPAH is mutations in BMPR2 gene. HPAH is a
progressive, fatal disease characterized by small pulmonary arterial remodeling involving vascular endothelium
and smooth muscle cells, which obliterate the vascular lumen. These remodeled vessels are always
surrounded by large numbers of bone marrow-derived cells (BMC) however, we do not fully understand the
exact role of these cells in HPAH pathogenesis. We have recently shown that transplant of Bmpr2 mutant
BMCs caused PAH in control (Ctrl) mice and transplant of Ctrl BMC in Bmpr2 mutant mice resulted in
attenuation of PAH. These data indicate that counter to what was previously thought, BMCs may have a causal
role in PAH. However we do not know the key cell type in the total BM population that is important, we do not
know mechanistically how the lineage-committed BMC in the lungs contribute to HPAH and further more and
importantly the extent of the therapeutic potential of these cells in reversing the HPAH lung phenotype. We
hypothesize that specific mutant BMC populations cause HPAH, and specific WT BMCs play a role in
disease attenuation and recovery. We propose to explore these hypotheses in 3 specific aims. 1) Test the
hypothesis that specific BMC populations have a causal role in HPAH. 2) Investigate the hypothesis that BM
cell transplantation can prevent or reverse established HPAH. 3) Determine the mechanism by which lineage
committed BMC populations contribute to the pathogenesis of HPAH. Our proposal sits at the intersection of
lung biology and BMC biology and is a collaborative effort between lung biologists, stem-cell biologists, and
clinicians and will produce a synergistic effect that is not easily matched by a single investigator. The rationale
for the proposed research is that better understanding of the role of BMCs in HPAH will lead to not only
significantly improved insight into disease pathogenesis but also whether BMCs are a useful therapeutic
option—an important point considering that effective long-term treatment options for HPAH are severely
limited. While this proposal is translational in scope it also presents an innovative paradigm that integrates
stem cell biology with lung biology. It is our expectation that we will: 1) develop a better understanding of the
role of BMC in HPAH; 2) determine the full therapeutic potential of BMCs in HPAH.

## Key facts

- **NIH application ID:** 9934000
- **Project number:** 5R01HL136748-04
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** RIZWAN HAMID
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $634,580
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9934000

## Citation

> US National Institutes of Health, RePORTER application 9934000, Role of bone marrow cells in pathogenesis and therapy of heritable pulmonary arterial hypertension (5R01HL136748-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9934000. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*