# Genomic and Circulating Predictors of PAH response

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $622,064

## Abstract

SUMMARY
Pulmonary arterial hypertension is a relentless disease characterized by vascular obliteration, right
heart failure and death. Although there are ten FDA-approved therapies in three classes for PAH,
none is curative and approximately 40% of patients are dead within 5 years of diagnosis. There is no
established approach to identify patients who will respond to a specific therapy and many patients
worsen while waiting for an effective therapy. The goals of this proposal are to improve outcomes in
PAH using the concepts of precision medicine through an advanced genetics and “Omics” approach
incorporating transcriptomics, proteomics and metabolomics. Within cohorts of unselected PAH
patients, there are two subsets with striking responses to therapy. One is a small subset that has a
marked reduction in pulmonary artery pressure acutely in response to vasodilators and a dramatic
long-term clinical response to calcium channel blocker therapy. We have recently published
peripheral blood transcriptomic and genomic signatures of calcium channel blocker responsive
patients differentiating them from non-responsive patients. The second subset is patients that have
marked improvement with parenteral prostacyclin therapy. We and others have reported
normalization of pulmonary arterial pressure in a subset of PAH patients treated with parenteral
prostacyclin therapy. In preliminary data, we have identified clinical predictors of long-term survival in
response to parenteral prostacyclin therapy and have found transcriptomic patterns that differentiate
these patients. We have also identified variability in expression of the prostacyclin receptor in
lymphoblastoids of control individuals and suppression of the receptor in PAH. We have preliminarily
identified genetic variants that regulate prostacyclin receptor expression and that differentiate patients
with good and poor responses to prostacyclin therapy. These data form the basis of our hypothesis
that peripheral blood-derived genetic and Omic profiles identify correlates of prostacyclin
responsiveness in PAH and can be exploited to understand mechanisms of drug efficacy and to
optimize patient care. In this grant we propose to 1) understand genetic variation contributing to
differential clinical response to prostacyclin therapy in PAH, 2) identify peripheral blood-derived Omic
profiles to identify patients with durable clinical responses to parenteral prostacyclin therapy, 3)
prospectively test our genetic and Omic profiles capacity to predict short-term responses to
prostacyclin therapy in PAH clinically treated with PPs. The long term goals of this proposal are to
better match a patient's unique biology to PP therapy, potentially improving survival in this highly
morbid disease.

## Key facts

- **NIH application ID:** 9926307
- **Project number:** 5R01HL142720-02
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Anna R Hemnes
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $622,064
- **Award type:** 5
- **Project period:** 2019-05-15 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9926307

## Citation

> US National Institutes of Health, RePORTER application 9926307, Genomic and Circulating Predictors of PAH response (5R01HL142720-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/9926307. Licensed CC0.

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