How two factors cause lymphatic malformations

“Two-hit” model for lymphatic malformations.

NIH-funded research Ut Southwestern Medical Center · NIH-11247922

This project looks at whether a KRAS gene change together with a growth signal causes lymphatic malformations in people with complex lymphatic anomalies.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionUt Southwestern Medical Center NIH-funded
Lab location1 site (Dallas, United States)
Project IDNIH-11247922 on NIH RePORTER

What this research studies

The team is using a new mouse model that turns on an active KRAS gene in lymphatic cells to mimic what is seen in patients with complex lymphatic anomalies (CLAs). They will compare effects in developing (newborn) versus adult lymphatic vessels and give lymphangiogenic signals like VEGF-C to see if both a genetic hit and an environmental growth signal are needed to form malformations. Researchers will examine tissues and cells to map the molecular pathways that drive disease and identify points drugs might target. Results are intended to point toward safer, more targeted treatments and to clarify when and how these malformations begin.

Who could benefit from this research

Good fit: People with complex lymphatic anomalies such as central conducting lymphatic anomaly (CCLA), generalized lymphatic anomaly (GLA), Gorham-Stout disease (GSD), or kaposiform lymphangiomatosis (KLA), especially those known to have KRAS mutations, are most relevant to this research.

Not a fit: Patients whose lymphatic disease is caused by unrelated gene changes or non-KRAS mechanisms may not benefit directly from this work.

Why it matters

Potential benefit: Could reveal why lymphatic malformations form and identify drug targets for safer, more effective treatments for people with CLAs.

How similar studies have performed: Prior work found KRAS mutations in CLA patients and mouse models showed KRAS can drive malformations in newborns, but testing the combined 'two-hit' role of KRAS plus growth signals is a new approach.

Where this research is happening

Dallas, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.