# Novel molecular and cardiac imaging paradigms for precision medicine in aortopathy

> **NIH NIH R01** · INDIANA UNIVERSITY INDIANAPOLIS · 2024 · $583,322

## Abstract

PROJECT SUMMARY/ABSTRACT
Thoracic aortic aneurysm (TAA) is a degenerative aortopathy that affects children and adults and predisposes
to sudden thoracic aortic dissection. Patients with TAA require lifelong cardiac care intended to prevent
progressive dilation or dissection. Cardiac decision-making requires projection of future risk, but the status quo
for establishing prognosis is not personalized and lacks precision. The basis for rapid progression versus stability
or improvement over time is not understood nor predictable using current approaches. Novel methods to classify
risk for disease progression upon diagnosis are urgently needed. Our long-term objective is to leverage
molecular and image analysis tools to create novel methods to classify risk of aortopathy progression precisely
and identify mechanisms amenable to future therapeutic targeting. Our first aim is to identify genetic variants
that are associated with increased or decreased longitudinal rate of aortic dilation, hypothesizing that single
nucleotide polymorphisms (SNPs) regulate inter-individual variability in TAA progression. We will perform whole
genome sequencing (WGS) in study participants who are receiving longitudinal pediatric aortopathy care.
Enrollment will occur at two pediatric cardiac centers with subspecialty aortopathy programs: Indiana University
Health’s Riley Hospital and Children’s Healthcare of Atlanta. We will test SNPs for their association with rates of
aortic dilation using mixed model analysis of serial aortic diameter measurements. In our second aim, we will
leverage our unique aortopathy tissue biobank to identify novel candidate SNPs in transcriptional regulatory
elements that contribute to TAA pathogenesis. We will perform deep RNA sequencing of flash frozen human
TAA tissues and controls and integrate these data with WGS to identify genes with differential allele-specific
expression in TAA. We will directly test the impacts of candidate SNPs in 3’-untranslated regions and enhancers
on allelic transcription using our high-throughput reporter assays in cultured human aortic smooth muscle cells.
For our third aim, in collaboration with biomedical engineers at Purdue University, we have pioneered a novel
automated algorithm that tracks aortic root kinematics across cardiac cycles and extracts morphological and
functional metrics using clinical echocardiography. We will establish a large normative data set of novel metrics
in young healthy subjects and compare metrics between TAA cases and matched controls. We hypothesize that
abnormal metrics portend increased rate of aortic dilation at follow-up, helping us predict clinical outcomes. Upon
completion, these aims will elucidate a genetic basis for transcriptional dysregulation in TAA, identify SNPs that
modify TAA progression, and advance echocardiographic phenotyping of the aortic root. Creation of a novel
classifier to predict risk for TAA progression, without significantly modifying existing clinical ...

## Key facts

- **NIH application ID:** 10779066
- **Project number:** 1R01HL171631-01
- **Recipient organization:** INDIANA UNIVERSITY INDIANAPOLIS
- **Principal Investigator:** Benjamin John Landis
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $583,322
- **Award type:** 1
- **Project period:** 2023-12-01 → 2028-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10779066

## Citation

> US National Institutes of Health, RePORTER application 10779066, Novel molecular and cardiac imaging paradigms for precision medicine in aortopathy (1R01HL171631-01). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10779066. Licensed CC0.

---

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