# Mouse Models for Systems Therapeutics Degenerative Diseases

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2020 · $522,028

## Abstract

Project summary
Thoracic aortic aneurysms (TAA) are life-threatening pathologies characterized by progressive dilation
associated with smooth muscle cell dysfunction and destructive extracellular matrix remodeling that ultimately
lead to tear and rupture of the vessel wall. Current management of TAA relies on early detection by routine
imaging and prophylactic repair by surgical procedures. The main goal of this proposal is to use systems
therapeutics as an unbiased tissue-level strategy to identify combinatorial treatments with repurposed
drugs that can efficaciously target TAA-related signaling pathways in mice with early onset,
progressively severe Marfan syndrome (MFS). This genetic model of TAA was chosen because the mutated
protein (fibrillin-1) regulates several key aspects of arterial function and homeostasis, including tissue integrity,
endothelial cell mechanotransduction, and angiotensin II and TGFβ signaling. Our proposal is organized into
two specific aims that combine experimental and computational approaches to elucidate the pathogenic
contributions of multiple signaling pathways and cell types in the fibrillin-1-deficient aortas of MFS mice (Aim
1); and predict and validate combinatorial drug treatments targeting disease-associated signals within and
across distinct wall compartments (Aim 2). Our system therapeutics strategy is expected to transform
MFS from a deadly arterial disease that requires surgical intervention to a chronic condition that can
be managed medically.

## Key facts

- **NIH application ID:** 9939459
- **Project number:** 5R01AR069307-04
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Srinivas Ravi V Iyengar
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $522,028
- **Award type:** 5
- **Project period:** 2017-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9939459

## Citation

> US National Institutes of Health, RePORTER application 9939459, Mouse Models for Systems Therapeutics Degenerative Diseases (5R01AR069307-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9939459. Licensed CC0.

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