# Reciprocal VEGFC/VEGFR3-CDH5 regulation of lymphatic and sinusoidal vascular growth

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2024 · $602,142

## Abstract

Project Summary
Sinusoidal and lymphatic vessel regeneration are predicted to improve treatment of
hematopoietic diseases and lymphedema, but are presently limited by an incomplete
understanding of the molecular and genetic pathways that control growth of these
specialized vascular beds. Prior studies by us and others have demonstrated that
VEGFC is required for fetal liver hematopoiesis, but a clear mechanism for this
requirement has not been identified. Our preliminary studies demonstrate that loss of
VEGFC/VEGFR3 function or gain of CDH5 function confers identical defects in
sinusoidal and lymphatic vascular growth. Further, our genetic studies demonstrate that
partial loss of CDH5 rescues both the anemia and edema conferred by the loss
sinusoidal and lymphatic vascular growth, respectively, in VEGFR3-deficient animals.
We hypothesize that a reciprocal VEGFC/VEGFR3-CDH5 regulatory loop controls
sinusoidal and lymphatic vascular growth. This proposal will test this hypothesis in vivo
and in vitro, investigate the molecular mechanism of this co-regulatory axis, and
determine whether manipulation of CDH5 can be used to stimulate sinusoidal and
lymphatic regeneration in mature animals. These studies are predicted to provide
fundamental new insights into sinusoidal and lymphatic vessel growth that may be
leveraged to treat patients with hematopoietic and lymphatic vascular diseases.

## Key facts

- **NIH application ID:** 10832012
- **Project number:** 5R01HL162795-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** MARK L KAHN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $602,142
- **Award type:** 5
- **Project period:** 2022-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832012

## Citation

> US National Institutes of Health, RePORTER application 10832012, Reciprocal VEGFC/VEGFR3-CDH5 regulation of lymphatic and sinusoidal vascular growth (5R01HL162795-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10832012. Licensed CC0.

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