NIH-backed project will investigate new treatments for lymphedema

Darci Fink, a researcher in South Dakota State University's Biosystems Networks and Transformative Research-Insight into Inflammation Center of Biomedical Research Excellence (BioSNTR-II COBRE) received a flagship grant from the National Institutes of Health to explore the underlying causes of lymphedema, a disfiguring disease that affects 10 million people in the U.S. 

A South Dakota State University researcher's discovery of two proteins critical to lymphatic valve formation has earned a highly competitive National Institutes of Health R01 grant to explore whether those proteins could unlock the first targeted treatments for lymphedema.

The chronic and incurable disease causes swelling, disfigurement and weakened immune surveillance and affects millions of people worldwide.

In the human body, the lymphatic system is a network of vessels that collects fluid leaking from blood capillaries into surrounding tissues. The lymphatic system filters this fluid — known as lymph — to be screened for pathogens by immune cells in the lymph nodes. The fluid is then returned to the bloodstream in a continuous cycle.

The lymphatic system is like a drainage system in the human body that prevents this leakage from causing significant damage. For the system to work effectively, it relies on lymphatic valves to keep fluid moving in the right direction. When these valves fail, excess fluid accumulates, which can lead to lymphedema and other immune system defects.

"Although lymphatics are essential for immune surveillance and fluid balance, we still have much to learn about how they work and what leads to dysfunction in disease," said Darci Fink, associate professor in SDSU's  Department of Chemistry, Biochemistry and Physics and the primary investigator on the project. "I am so grateful to my fantastic lab team, collaborators, colleagues, and mentors in the COBRE research center who helped build the foundation for this project. We are thrilled to have the opportunity to test our hypotheses and contribute insights that could one day improve patient care."

Lymphedema is one of the most common chronic diseases in the world, affecting an estimated 250 million. In the U.S., roughly 10 million people are dealing with this condition that is currently considered "incurable." While some are born with the condition, far more develop what is called "secondary lymphedema" following cancer treatment. Those undergoing breast cancer treatment are particularly at risk because surgery and radiation therapy often damage the lymphatic system.

Fink and her team previously discovered a small structure on lymphatic cells called the primary cilium. The cilium is like an antenna that can detect physical and chemical signals from the cell’s environment. The team identified lymphatic functions for two transport proteins – IFT20 and IFT74 – that help build the cilium and play connected roles in detecting fluid flow, triggering valve development, and trafficking other molecules to stabilize and mature the valves.

In this project, Fink and her research team will dive deeper into how these proteins function and aim to build a comprehensive molecular model of how these proteins create and stabilize lymphatic valves. The research team believes that by understanding the fundamental role of these proteins, they may identify new targets for treatments to restore valve function in lymphedema patients.

Currently, no cure exists for lymphedema. Those afflicted can only manage symptoms through compression and massage therapy. Worse, due to its destruction of immune surveillance, lymphedema can create an environment ripe for bacterial infections. The research being conducted at SDSU will open new pathways for finding treatments that target the disease's underlying causes.

"Obtaining an NIH R01 grant is an outstanding achievement, firmly launching Dr. Fink’s biomedical research career," said Adam Hoppe, professor and director of SDSU's Biosystems Networks and Transformative Research-Insight into Inflammation Center of Biomedical Research Excellence. "Her innovative and rigorous approaches supported by this grant will lay the foundation for future biomedical therapies impacting lymphedema and immune regulation."

The five-year project is being funded through a $2 million grant from NIH's National Heart, Lung, and Blood Institute. SDSU's BioSNTR-II COBRE center is the university's first NIH-backed research center and is designed to strengthen the nation's research capacity in biomedical studies. 

Research reported in this publication was supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number P20GM135008 and the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number R01HL175395.  

The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.