# Mechanisms of fibrosis in post-surgical lymphedema

> **NIH NIH R01** · SLOAN-KETTERING INST CAN RESEARCH · 2020 · $897,335

## Abstract

Project Summary
This proposal is significant because we aim to develop novel treatments for secondary lymphedema, a common
and morbid complication of cancer treatment. This is important because current therapies for this disease are
palliative and inadequate. In our previous studies, we have shown that the pathology of lymphedema is
secondary to progressive fibrosis and is mediated by chronic T-helper (CD4+) cell inflammation and T-helper 2
(Th2) differentiation. We have used this information to develop novel therapies for the treatment of secondary
lymphedema and have recently translated our work from the bench to the bedside in an investigator-initiated trial
using Th2 cytokine neutralizing antibodies.
 The objective of this application is to identify the cellular mechanisms that initiate CD4+ cell inflammatory
responses following lymphatic injury. This objective is a logical extension of our previous work and should identify
additional targets that can be targeted pharmacologically to treat/prevent lymphedema. Our long-term objective
is to use the information we gain from this basic understanding of lymphedema to develop therapies that disrupt
the cycle of events that promote progressive fibrosis and lymphatic dysfunction. Our approach is innovative
since we use a combination of mouse models and clinical specimens to dissect the cellular mechanisms of
lymphedema pathology. Our group is uniquely positioned to accomplish our goals on the basis of our
multidisciplinary team, our access to clinical tissues, and our novel mouse models. We plan to achieve our
objectives using 2 specific aims:
Aim 1. Determine how lymphatic injury activates CD4+ cells. This aim will use clinical samples and mouse
models to test the hypothesis that keratinocytes play a key role in the activation and migration of CD4+ cells to
lymphedematous tissues. In addition, we will test the hypothesis that single nucleotide polymorphisms in immune
response genes will increase the risk of lymphedema.
Aim 3. Determine how inflammation impairs lymphatic function. This aim will test the hypothesis that
inflammatory responses in lymphedema impair lymphatic function by multiple effects, including tissue and
lymphatic fibrosis, perilymphatic inflammation, and impaired formation of collateral lymphatic vessels.

## Key facts

- **NIH application ID:** 9872198
- **Project number:** 5R01HL111130-08
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** Babak J Mehrara
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $897,335
- **Award type:** 5
- **Project period:** 2012-09-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9872198

## Citation

> US National Institutes of Health, RePORTER application 9872198, Mechanisms of fibrosis in post-surgical lymphedema (5R01HL111130-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9872198. Licensed CC0.

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