# Vascular-targeting genomic and genetic strategies for acute chest syndrome

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2021 · $588,405

## Abstract

ABSTRACT
The PI of this application is a physician-scientists with a career focus on developing improved care for patients
with sickle cell disease (SCD). The acute chest syndrome (ACS) represents a serious, potentially fatal
inflammatory lung injury syndrome occurring in patients with SCD. ACS shares many features of the
inflammatory lung injury associated with acute lung injury and is the second most common cause of SCD
hospitalization, is a major cause of acute and chronic SCD morbidity and mortality, is the leading cause of SCD
ICU admission and premature death. There is increasing appreciation that ACS is an acute hypoxia-induced
lung injury syndrome targeting the lung endothelium in response to multiple exogenous insults or triggers
leading to pulmonary erythrocyte sequestration, an exaggerated inflammatory response, increased expression
of adhesion molecules and impairment of pulmonary vascular function. In this highly translational proposal we
will address the hypothesis that vascular-targeted genetic and genomic strategies for ACS will lead to better
understanding of the pathobiology of ACS, generate novel ACS biomarkers in SCD patients and produce
vascular-specific therapies for ameliorating this devastating health disparity. To address this hypothesis, in
Specific Aim #1 we will identify and validate potentially functional novel single nucleotide polymorphisms
(SNPs) and epigenetic modifiers that modulate ACS susceptibility. Specific Aim #2 will interrogate necroptosis
as a molecular and therapeutic target in murine ACS. In Specific Aim #3 discover and validate biochemical and
genetic necroptosis-centric biomarkers of ACS risk and a genomic signature for mortality in SCD patients.
Together, these highly translational approaches hold the promise to identify novel targets and biomarkers that
may lead to better treatment options for patients with ACS.

## Key facts

- **NIH application ID:** 10213108
- **Project number:** 5R01HL111656-09
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Roberto F. Machado
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $588,405
- **Award type:** 5
- **Project period:** 2013-02-05 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10213108

## Citation

> US National Institutes of Health, RePORTER application 10213108, Vascular-targeting genomic and genetic strategies for acute chest syndrome (5R01HL111656-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10213108. Licensed CC0.

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