# Diversity Supplement:  Systems Pharmacology Model of Cardiac Hypertrophy

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $50,330

## Abstract

SUMMARY OF THE FUNDED PARENT GRANT
Heart failure is defined as the inability of cardiac output to meet demand. Cardiac hypertrophy,
defined as an increase in cardiomyocyte size and heart muscle mass, leads to maladaptive
remodeling and is a significant precursor of heart failure. We aim to overcome the past
obstacles of focusing on a single signaling molecule by employing a systems approach that
considers the more extensive network of signaling interactions and FDA-approved drugs that
are viable candidates for drug repurposing. Our overall goal is to identify drugs and network
mechanisms as therapeutic targets to control cardiac hypertrophy. To achieve this goal, we will
test the overall hypothesis that a systems pharmacology network model can accurately
predict the context-dependent effects of drugs on cardiomyocyte hypertrophy in vitro
and in vivo. In Specific Aim 1, we will apply a systems pharmacology model to predict drugs
and drug combinations that cause context-dependent regulation of cardiomyocyte hypertrophy.
We will develop a computational model that integrates the cardiomyocyte signaling network with
the pharmacologic mechanisms of FDA-approved drugs. We will then use this model to predict
the drug combinations and network mechanisms that inhibit cardiomyocyte hypertrophy under
distinct environmental contexts. In Specific Aim 2, we will validate our model predictions of
candidate drugs using cultured rat and human cardiomyocytes to test the context-dependent
inhibition of cardiomyocyte hypertrophy. In Specific Aim 3, we will translate the model and cell-
based experimental data to in vivo mouse models of cardiac hypertrophy and determine
whether the modeling accurately predicts the effects of drugs in a context-dependent manner.
Overall, these studies will establish a systems pharmacology model, new computational insights
into how drugs modulate cardiac hypertrophy, and a wealth of new experimental data that will
validate these predictions.

## Key facts

- **NIH application ID:** 11098995
- **Project number:** 3R01HL162925-03S1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Jeffrey J. Saucerman
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $50,330
- **Award type:** 3
- **Project period:** 2022-04-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11098995

## Citation

> US National Institutes of Health, RePORTER application 11098995, Diversity Supplement:  Systems Pharmacology Model of Cardiac Hypertrophy (3R01HL162925-03S1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/11098995. Licensed CC0.

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