# Pathobiology of lymphatic function: in vivo near-infrared lymphatic imaging

> **NIH NIH F32** · BOSTON CHILDREN'S HOSPITAL · 2020 · $15,541

## Abstract

Project Summary/Abstract
The lymphatic system, with its intrinsic physiologic functions in cellular homeostasis, immune cell trafficking, and
lipid absorption, contributes significantly to the pathogenesis of metabolic disorders. Lymphatic dysfunction
shows strong positive correlation with obesity and results in increased susceptibility to lymphedema. Defective
lymphatic vessels by lacking one allele of Prox1, a transcription factor that regulates lymphatic endothelial cell
differentiation, induces adult-onset obesity, suggesting that lymphatic dysfunction directly contributes to the
development of metabolic disorders. In contrast, metabolic diseases exhibit lymphatic dysregulation that
contributes to the development of further pathological conditions including inflammation, impaired lipid absorption,
or elevated chyle accumulation coupled with increased susceptibility of edema. However, how lymphatic
dysfunctions aggravate metabolic diseases, and conversely, how metabolic disorders induce lymphatic
dysfunctions are unknown but highly relevant medical questions. Our preliminary data show that deficiency of
Foxc2, a critical regulator of lymphangiogenesis, elevates VEGFR3 signaling and causes an increase in
lymphangiogenesis both in vivo and in vitro. In addition, loss of lymphatic endothelial Foxc2 enhanced collecting
lymphatic function and lymph flow in adult mice. Hence, we will identify 1) the therapeutic potential of targeting
Foxc2 in lymphatic dysfunction in metabolic disorders and 2) the underlying molecular mechanisms by which
Foxc2 regulates adult lymphangiogenesis and lymphatic function. Using the innovative conditional lymphatic
endothelial specific Foxc2 gain-of-function or Foxc2 loss-of-function mice, we will test the direct role of Foxc2 in
pathophysiological lymphatic regeneration and function in metabolic diseases. In addition, we will utilize highly
sensitive NIR imaging approaches to assess in vivo lymph transport in our live transgenic animals. Finally, we
will determine underlying molecular mechanisms by which Foxc2 regulates lymphangiogenesis and lymphatic
function. We will use Chip, immunoblotting, co-immunoprecipitation, and luciferase reporters to complete this in-
depth investigation. Thus, this proposal will identify important targets that modulate lymphangiogenesis and
lymphatic function in mature lymphatic vessels, which could potentially provide diagnostic tools or therapies to
improve lymph transport and, consequently mitigate lymphatic dysfunctions in patients with Metabolic Syndrome
or secondary lymphedema.

## Key facts

- **NIH application ID:** 10023173
- **Project number:** 5F32HL149326-02
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Yang Lee
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $15,541
- **Award type:** 5
- **Project period:** 2019-09-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023173

## Citation

> US National Institutes of Health, RePORTER application 10023173, Pathobiology of lymphatic function: in vivo near-infrared lymphatic imaging (5F32HL149326-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10023173. Licensed CC0.

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