# Retinoic Acid Induced Lymphangiogenesis for Post-Surgical Lymphedema

> **NIH NIH R01** · RUTGERS BIOMEDICAL AND HEALTH SCIENCES · 2024 · $645,721

## Abstract

Lymphedema is an incurable condition characterized by lymphatic obstruction, tissue swelling,
immune dysfunction, and fibrosis after lymphatic injury. Lymphedema affects 5 million Americans and
is associated with poor quality of life due to extremity disability, disfigurement, and risk for recurrent
limb-threatening infection. In the US, lymphedema is most commonly a consequence of lymph node
dissection for the treatment of solid tumors such as breast or pelvic cancer. Despite the fact that
lymphedema is common and morbid, there are currently no effective drug treatments. Using
preclinical rodent models of lymphedema, we have shown that 9-cis retinoic acid (RA) significantly
accelerates lymphatic regeneration following injury, restores functional lymphatic drainage, and
prevents development of lymphedema. Our overarching hypothesis is that RA-mediated
lymphangiogenesis is a promising therapy for secondary lymphedema. The objective of this proposal,
which is the first logical step towards implementing this treatment clinically, is to increase our
understanding of the mechanisms by which RAs regulate lymphangiogenesis and develop a
translational framework for the use of these compounds. The specific aims of this proposal include
Aim 1: Determine how RA selectively induces lymphangiogenesis; Aim 2: Elucidate the roles of FGFR
and VEGFR signaling in RA-mediated lymphangiogenesis; and Aim 3: Use early biomarkers of
lymphatic insufficiency to develop a predictive model that can guide initiation of RA therapy. Based
on the current lack of effective therapy, it is clear that there is a need to develop an etiology-focused
treatment for post-surgical lymphedema. The proposed studies will address important mechanistic
questions regarding RA mediated lymphangiogenesis and also develop an early biomarker based
predictive model that will guide treatment windows for RA therapy. The proposed work will
significantly improve our understanding of RA-mediated lymphangiogenesis as well as support clinical
translation of a RA as a preventative treatment regimen for post-surgical lymphedema.

## Key facts

- **NIH application ID:** 11063577
- **Project number:** 7R01HL157626-04
- **Recipient organization:** RUTGERS BIOMEDICAL AND HEALTH SCIENCES
- **Principal Investigator:** Alex K. Wong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $645,721
- **Award type:** 7
- **Project period:** 2021-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11063577

## Citation

> US National Institutes of Health, RePORTER application 11063577, Retinoic Acid Induced Lymphangiogenesis for Post-Surgical Lymphedema (7R01HL157626-04). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/11063577. Licensed CC0.

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