# Identification of immunotherapeutic targets in cardiovascular disease

> **NIH NIH R00** · WASHINGTON UNIVERSITY · 2020 · $249,000

## Abstract

Project Summary.
Myocardial infarction (MI) and neointimal hyperplasia (NH) are common comorbidities in patients with coronary
heart disease - an insidious condition that comprises the majority of all cardiovascular disease (CVD)-related
mortality. Following acute MI, occlusion of the coronary vasculature leads to persistent cardiac fibrosis and im-
paired cardiac function. Restoration of coronary blood flow is often achieved by stent placement, but rates of
excessive cellular ingrowth and pathologic NH formation remain high. Thus, optimal treatment strategies for
acute MI must focus on reducing both cardiac fibrosis and neointima formation. Increasing evidence suggests
inflammation regulates CVD progression, but little work has focused on the development of targeted immuno-
modulatory therapies. Therefore, the objectives of this proposal are: 1) develop novel experimental and compu-
tational approaches to identify and evaluate targeted immunotherapeutic treatment strategies in CVD and 2)
establish a concentrated period of training that will equip Dr. Bersi with the expertise needed to transition to an
independent research position. In the mentored K99 phase, Dr. Bersi will investigate how expression of the cell-
cell adhesion protein cadherin-11 (CDH11) in diverse cellular lineages regulates inflammation and tissue remod-
eling associated with MI and NH (Aim 1). By leveraging the immunomodulatory potential of CDH11, he will cor-
relate tissue-specific remodeling with immune cell localization and cytokine secretion following concomitant car-
diovascular injury. Experimentally-informed computational models of immune-mediated collagen deposition and
smooth muscle cell proliferation will be used to identify the primary molecular and cellular drivers of tissue-
specific injury responses (Aim 2). In the independent R00 phase, Dr. Bersi will utilize the proposed in silico
models to generate novel immunotherapeutic hypotheses (Aim 2) and will evaluate model predictions by as-
sessing the efficacy of rationally-designed immunotherapeutic treatments on the reduction of pathologic tissue
remodeling in MI and NH (Aim 3). Though Dr. Bersi has significant expertise in soft tissue biomechanics and
computational modeling, additional intellectual and technical training will be needed to realize his career goals
of investigating the multiscale relationship between mechanics and inflammation in CVD. The Merryman and
Harrison labs are ideal locations to acquire such training as Dr. Merryman is an expert in cardiopulmonary mech-
anobiology and Dr. Harrison is an expert in cardiovascular immunology and pharmacology. The training received
throughout this award will allow Dr. Bersi to successfully transition to an independent research position and lead
a multi-faceted, R01-funded, research laboratory focused on mechanics, modeling, and inflammation in CVD. In
summary, Dr. Bersi will utilize this K99/R00 award to establish multiscale experimental and computational tech-...

## Key facts

- **NIH application ID:** 10199268
- **Project number:** 4R00HL146951-02
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** MATTHEW Ryan BERSI
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $249,000
- **Award type:** 4N
- **Project period:** 2020-09-04 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10199268

## Citation

> US National Institutes of Health, RePORTER application 10199268, Identification of immunotherapeutic targets in cardiovascular disease (4R00HL146951-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10199268. Licensed CC0.

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