|  Gaps in the Field of Lymphatic Research  |  2026–27 Update  |  6
9. The Role of Lymphatics in Acute Injury, 
Chronic Disease, and Sex-Related Differences 
in Disease Outcomes 
• Better understanding of the lymphatic system  
and lymphatic valves in obesity, lipedema, and 
lymphedema.
• How does aging impact lymphatic biology and 
function? Do cells change (i.e., button junctions 
increasing)?
• Special emphasis on the impact of sex on lymphatic 
function and dysfunction as lymphatic diseases 
impact women.
• How are lymphatics involved in metabolic syndrome 
and chronic inflammation?
• How are lymphatics involved in the development  
of osteoarthritis?
• How are lymphatics involved in proper wound 
healing and fighting infections?
• How are lymphatics involved in neurological 
disorders such as stroke, dementia, and traumatic 
brain injury?
• Lymphatic involvement in musculoskeletal injury, 
repair, and regeneration.
• Investigating lymphatic physiology in the context of 
heart failure, lung disease, kidney disease.
• Impact of the restoration of lymph flow on healing 
and change in disease outcomes.
• Study how inflammatory bowel disease affects 
lymphatic vasculature and how it is associated  
with immunity.
10. Bench to Bedside Technologies
• Need to understand the gaps in pathological 
processes that have been identified such as 
inflammation and lymphangiogenesis. 
• Need to identify causative mutations in novel genes 
underpinning primary lymphedema and complex 
lymphatic and vascular anomalies in humans.
• Need for development of cell therapy or biomaterials 
that can improve lymphatic regeneration.
BASIC SCIENCE RESEARCH: 
GAPS AND NEEDS FOR RARE 
LYMPHATIC DISEASES
• How is the microenvironment altered in complex 
lymphatic anomaly (CLA) tissues and does it 
contribute to disease progression?
• What is the full complement of CLA-causing  
genetic mutations? Is it more than “one hit”  
that causes mutations?
• What makes the responsible somatic mutations for  
CLAs different from cancer causing mutations?
• What is the best method to genotype patients?  
Can we use cell-free DNA or circulating  
biomarkers to diagnose CLAs and monitor  
response to treatments?
• Are there other circulating diagnostic biomarkers  
for CLA?
• How do CLA-causing genetic mutations affect 
different LEC populations and do mutant LECs  
affect normal LECs?
• Do CLA-causing genetic mutations affect lymphatic 
vessel contractility and permeability?
• What other genes, factors, and pathways contribute  
to the pathogenesis of vascular and lymphatic 
anomalies?
• How do mutant endothelial cells affect normal 
endothelial cells?
• Why do lymphatics invade bone? Is it just  
by chance?
• What causes coagulopathy (trapping of platelets  
and clotting factors) in some patients presenting  
with complex lymphatic anomalies?
• What causes the LECs to become spindle shaped? 
Do these abnormal cells affect surrounding cells? 
How?
• Is crosstalk between LECs and osteoclasts important 
for the progression of CLAs?
• We need cell lines that will allow in vitro work and  
will allow in vivo xenografts or allografts. 
• We need genetically engineered animal models.
• We need a repository of biospecimens (blood,  
body fluids, and tissue).
• How does the chikungunya virus infect LECs and 
cause lymphatic injury, and can we create therapies 
against it?

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