b'9. The Role of Lymphatics in Acute Injury,BASIC SCIENCE RESEARCH: Chronic Disease, and Sex-Related DifferencesGAPS AND NEEDS FOR RARE in Disease Outcomes Better understanding of the lymphatic system LYMPHATIC DISEASES and lymphatic valves in obesity, lipedema, andHow is the microenvironment altered in complexlymphedema. lymphatic anomaly (CLA) tissues and does itHow does aging impact lymphatic biology andcontribute to disease progression?function? Do cells change (i.e., button junctionsWhat is the full complement of CLA-causing increasing)? genetic mutations? Is it more than one hitSpecial emphasis on the impact of sex on lymphaticthat causes mutations? function and dysfunction as lymphatic diseasesWhat makes the responsible somatic mutations for impact women. CLAs different from cancer causing mutations?How are lymphatics involved in metabolic syndrome What is the best method to genotype patients? and chronic inflammation? Can we use cell-free DNA or circulatingHow are lymphatics involved in the development biomarkers to diagnose CLAs and monitor of osteoarthritis? response to treatments? How are lymphatics involved in proper woundAre there other circulating diagnostic biomarkershealing and fighting infections? for CLA?How are lymphatics involved in neurologicalHow do CLA-causing genetic mutations affectdisorders such as stroke, dementia, and traumaticdifferent LEC populations and do mutant LECsbrain injury? affect normal LECs?Lymphatic involvement in musculoskeletal injury, Do CLA-causing genetic mutations affect lymphatic repair, and regeneration. vessel contractility and permeability? Investigating lymphatic physiology in the context ofWhat other genes, factors, and pathways contributeheart failure, lung disease, kidney disease. to the pathogenesis of vascular and lymphatic Impact of the restoration of lymph flow on healinganomalies? and change in disease outcomes. How do mutant endothelial cells affect normalStudy how inflammatory bowel disease affectsendothelial cells? lymphatic vasculature and how it is associated Why do lymphatics invade bone? Is it just with immunity. by chance?What causes coagulopathy (trapping of platelets10. Bench to Bedside Technologiesand clotting factors) in some patients presentingNeed to understand the gaps in pathologicalwith complex lymphatic anomalies? processes that have been identified such asWhat causes the LECs to become spindle shaped?inflammation and lymphangiogenesis.Do these abnormal cells affect surrounding cells? Need to identify causative mutations in novel genesHow? underpinning primary lymphedema and complexIs crosstalk between LECs and osteoclasts importantlymphatic and vascular anomalies in humans. for the progression of CLAs?Need for development of cell therapy or biomaterialsWe need cell lines that will allow in vitro work andthat can improve lymphatic regeneration. 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 andcause lymphatic injury, and can we create therapies against it?|Gaps in the Field of Lymphatic Research|2024 Update|6'