# Regeneration and remodeling of collecting lymphatic vessels post-injury

> **NIH NIH F32** · MASSACHUSETTS GENERAL HOSPITAL · 2021 · $65,994

## Abstract

SUMMARY
Many surgical insults—such as lymph node dissection and lymph node biopsy —can cause damage to the
lymphatic vessels, particularly when combined with radiotherapy, resulting in long-term lymphatic dysfunction
and the formation of lymphedema. Understanding the mechanisms of lymphatic regeneration after surgery and
cancer treatment is crucial to prevent lymphedema and develop efficient lymphedema therapy. Despite the
prevalence of lymphedema, it is not clear whether collecting vessels remodel/regenerate post-injury and
mechanisms of such growth and remodeling response are unknown. A disrupted lymphatic network induces
sustained fluid loads in the remaining network that drives lymphatic dysfunction. Improper collateralization and
collecting vessel remodeling due to sustained loads can cause a maladaptive remodeling response. Here I aim
to develop an understanding of lymphatic vessel remodeling, repair and dysfunction in the context of a disrupted
network using sophisticated lymphatic imaging, complex mouse models, and computational modeling. I will
investigate the mechanisms and modes by which lymph flow drives lymphatic remodeling and regrowth. I will
test whether collecting lymphatic vessels regrow/remodel following injury and determine the effect of lymph flow
on this response (Aim 1). I will also test whether there is a causal relationship between altered lymph flow and
activation of lymphangiogenic pathways using genetic mouse models. Further, I will determine the dynamics of
collateral growth at the injury site in the context of a disrupted network and altered lymph flow in our mouse
model (Aim 2). I will also use a 3D culture system to study the dynamics of collateral growth from pre-existing
collecting vessels under flow and pressure conditions in vitro. Computational modeling will complement Aim 2 to
better understand the relationship between structural remodeling and alteration of lymph flow dynamics. With
the completion of this project, I will provide insight into preventive strategies and better therapeutic interventions
for lymphedema therapy.
I have extensive training in lymphatic bioengineering, lymphatic imaging, image processing, isolated lymphatic
vessel experiments and computational modeling from my doctoral training. This project will leverage this training
in the labs of my postdoctoral advisors—Dr. Padera and Dr. Munn—who are leaders in the field of lymphatic
research and biology. Dr Padera’s lab has developed state-of-the-art lymphatic imaging tools to precisely
measure lymph flow rate, dynamic intravital microscopy of lymph nodes and animal models of lymphatic
diseases. Dr Munn’s lab has developed in vitro models of angiogenesis, computational models of angiogenesis
and lymphatic transport, bioengineered cell-culture systems and image processing tools to track cells. This
unique training environment will allow me to successfully complete the aims of this proposal.

## Key facts

- **NIH application ID:** 10156902
- **Project number:** 1F32HL156654-01
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Mohammad Razavi Rizi
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $65,994
- **Award type:** 1
- **Project period:** 2021-12-01 → 2024-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10156902

## Citation

> US National Institutes of Health, RePORTER application 10156902, Regeneration and remodeling of collecting lymphatic vessels post-injury (1F32HL156654-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10156902. Licensed CC0.

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