A recent discovery by scientists at OMRF could aid in the development of potential therapies for lymphedema.
Lymphedema is a disease characterized by dramatic and painful swelling in the limbs that occurs when there are defects in lymphatic vessels. It can result from mutations, surgery, radiation treatment for cancer or infection. There is no known cure.
OMRF scientist Sathish Srinivasan, Ph.D., and his team study the chains of events in cells that control the development of lymphatic vessels. When something goes wrong in one of these events, called a cell signaling pathway, it results in lymphedema — but signaling pathways can be targeted with medication.
In new research published in the Journal of Clinical Investigation Insight, Srinivasan and his colleagues have discovered that communication between three of these signaling pathways — VEGF-C, S1PR1 and shear stress — regulates healthy lymphatic vessel growth and development.
“Although the pathways were known, their interaction wasn’t. Understanding this communication could lead to the development of medications that can promote the regrowth of damaged lymphatic vessels and potentially lead to relief for people with lymphedema,” explained Srinivasan, whose lab is part of OMRF’s Cardiovascular Biology Research Program.
Srinivasan joined OMRF from St. Jude’s Children’s Research Hospital in 2013. His lab has identified several signaling pathways that regulate lymphatic vascular development.
“One of the most encouraging elements of this research is that one of the pathways, S1PR1, is a time-tested therapeutic target. A large number of drugs already exist that target it,” said Lijun Xia, M.D., Ph.D., who leads the Cardiovascular Biology Research Program at OMRF. “This work will provide mechanistic insights into lymphatic vessels that may lead to new therapeutic interventions for lymphedema.”
Srinivasan said his lab will now dissect the relationship between the pathways to see if they can promote lymphatic vessel growth in research models of lymphedema.
Other OMRF researchers who contributed to this research were Boksik Cha, Ph.D., Lijuan Chen, Ph.D., Xin Geng, Ph.D., Yen-Chun Ho, Ph.D., and Riaj Mahamud, Ph.D.
The work was supported by funding from the National Heart, Lung and Blood Institute (R01HL131652 and R01HL133216), National Institute of General Medical Sciences (P20 GM103441), the Oklahoma Center for Adult Stem Cell Research and the American Heart Association.