# Precision nanomedicine targeting novel endothelial mechano-sensing mechanisms

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2023 · $811,040

## Abstract

PROJECT SUMMARY
 Endothelial mechano-transduction mechanisms are instrumental to vascular health and disease but
targeting disease-causing mechano-sensing pathways remains extremely challenging. For instance,
atherosclerosis preferentially develops at arterial curvatures and bifurcations where disturbed blood flow
activates endothelium; however, current atherosclerosis therapies mainly target systematic risk factors but not
the vasculature per se. This underscores the significance and unique opportunity to identify and target novel
mechanosensitive mechanisms in activated endothelium subjected to disturbed flow. This proposal aims to first
delineate novel endothelial mechano-sensing mechanisms and moreover, devise innovative precision
nanomedicine approaches targeting these disease-causing mechano-sensitive pathways.
 This R35 mechanism will provide us a unique opportunity to synergistically combine our efforts in
endothelial biology (R01 HL136765) and vascular nanomedicine (R01 HL138223), testing paradigm shift
hypotheses related to endothelial mechanotransduction and addressing an unmet medical need in vascular
therapies. Specifically, seminal work from us and colleagues along with our unpublished data identified three
new layers of molecular controls of endothelial mechano-transduction: epi-genome (DNA chemical
modification), epi-transcriptome (mRNA chemical modifications) and metabolism (glycolysis and oxidative
phosphorylation). The overall goals of this project are to 1) identify novel regulators governing the endothelial
epi-genomic, epi-transcriptomic, and metabolic responses to blood flow and 2) engineer innovative
nanoparticles which target each of these pathways treating vascular complications in vivo. The scientific
premise is that innovative nanoparticles can effectively deliver therapeutic nucleotides targeting these
mechano-sensitive pathways in activated endothelium.
 This proposal addresses a significant knowledge gap in endothelial biology and an uncharted territory
in vascular medicine, research directions being pursued by only a small number of laboratories world-wide.
Our team has laid much the groundwork in developing multidisciplinary knowledge, technologies, and animal
models necessary to investigate new endothelial mechanotransduction paradigms and moreover, devise
precision nanomedicine strategies for future tailor-made vascular therapies. Successful completion of the
proposal will establish a proof of concept of targeted nanomedicine in vascular wall-based therapies. The
proposed studies should further preclinical development and eventual clinical testing of new therapeutic
strategies to treat vascular diseases.

## Key facts

- **NIH application ID:** 10630052
- **Project number:** 5R35HL161244-02
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Yun Fang
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $811,040
- **Award type:** 5
- **Project period:** 2022-06-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10630052

## Citation

> US National Institutes of Health, RePORTER application 10630052, Precision nanomedicine targeting novel endothelial mechano-sensing mechanisms (5R35HL161244-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10630052. Licensed CC0.

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