A5025121973- Lymphatic System and Diseases
- Sympathectomy and Hyperhidrosis Treatments
- Advanced Differential Geometry Research
- Lymphatic Disorders and Treatments
- Hippo pathway signaling and YAP/TAZ
- Wnt/β-catenin signaling in development and cancer
- Congenital heart defects research
- Cardiovascular and Diving-Related Complications
- Vascular Malformations and Hemangiomas
- Angiogenesis and VEGF in Cancer
- Planarian Biology and Electrostimulation
- Cardiac Valve Diseases and Treatments
- Kruppel-like factors research
- Neonatal Respiratory Health Research
Oklahoma Medical Research Foundation
2015-2022
University of Oklahoma Health Sciences Center
2016-2022
Lymphatic vasculature regulates fluid homeostasis by returning interstitial to blood circulation. endothelial cells (LECs) are the building blocks of entire lymphatic vasculature. LECs originate as a homogeneous population predominantly from embryonic veins and undergo stepwise morphogenesis become capillaries, collecting vessels or valves. The molecular mechanisms underlying remain be fully understood. Here we show that canonical Wnt/β-catenin signaling is necessary for vascular...
Lymph is returned to the blood circulation exclusively via four lymphovenous valves (LVVs). Despite their vital importance, architecture and development of LVVs poorly understood. We analyzed formation at molecular ultrastructural levels during mouse embryogenesis identified three critical steps. First, LVV-forming endothelial cells (LVV-ECs) differentiate from PROX1+ progenitors delaminate luminal side veins. Second, LVV-ECs aggregate, align perpendicular direction lymph flow establish...
Wnt/β-catenin signaling is necessary for lymphatic vascular development. Oscillatory shear stress (OSS) enhances in cultured endothelial cells (LECs) to induce expression of the lymphedema-associated transcription factors GATA2 and FOXC2. However, mechanisms by which OSS regulates FOXC2 are unknown. We show that activates autocrine LECs vitro. Tissue-specific deletion Wntless, required secretion Wnt ligands, reveals smooth muscle complementary sources ligands regulate development vivo....
During the growth of lymphatic vessels (lymphangiogenesis), endothelial cells (LECs) at growing front sprout by forming filopodia. Those tip are not exposed to circulating lymph, as they lumenized. In contrast, LECs that trail shear stress, become quiescent, and remodel into stable vessels. The mechanisms coordinate opposed activities sprouting maturation remain poorly understood. Here, we show canonical cell marker Delta-like 4 (DLL4) promotes lymphangiogenesis enhancing VEGF-C/VEGF...
Impaired lymphangiogenesis is a complication of chronic complex diseases, including diabetes. VEGF-C/VEGFR3 signaling promotes lymphangiogenesis, but how this pathway affected in diabetes remains poorly understood. We previously demonstrated that loss epsins 1 and 2 lymphatic endothelial cells (LECs) prevented VEGF-C–induced VEGFR3 from endocytosis degradation. Here, we report attenuated corneal micropocket Matrigel plug assays WT mice not with inducible lymphatic-specific deficiency...
Lymphatic vasculature is an integral part of digestive, immune and circulatory systems. The homeobox transcription factor PROX1 necessary for the development lymphatic vessels, valves (LVs) lymphovenous (LVVs). We others previously reported a feedback loop between vascular endothelial growth factor-C (VEGF-C) signaling. promotes expression VEGF-C receptor VEGFR3 in cells (LECs). In turn, signaling maintains LECs. However, mechanisms PROX1/VEGF-C remain poorly understood. Whether LV LVV also...
Mutations in the transcription factor GATA2 cause lymphedema. is necessary for development of lymphatic valves and lymphovenous valves, patterning vessels. Here, we report that not valvular endothelial cell (VEC) differentiation. Instead, required VEC maintenance morphogenesis. also expression junction molecules VE-cadherin claudin 5 We identified miR-126 as a target GATA2, miR-126-/- embryos recapitulate phenotypes mice lacking GATA2. Primary human cells (HLECs) (HLECΔGATA2) have altered...
ABSTRACT Mutations in the transcription factor GATA2 cause lymphedema. is necessary for development of lymphatic valves (LVs) and lymphovenous (LVVs), patterning vessels. Here, we report that not valvular endothelial cell (VEC) differentiation. Instead, required VEC maintenance morphogenesis. also expression junction molecules VE-Cadherin Claudin5 We identified miR-126 as a target GATA2, −/− embryos recapitulate phenotypes mice lacking GATA2. Primary human cells (HLECs) (GATA2 ΔHLEC ) have...
Abstract Introduction Lymphatic vessels collect interstitial fluid, immune cells, and digested lipids return these bodily fluids to blood through two pairs of lymphovenous valves (LVVs). Like other cardiovascular LVVs prevent the backflow into lymphatic vessels. In addition LVVs, platelets are necessary entry Platelet thrombi observed at suggesting that function in synergy regulate blood/lymphatic separation. Objectives The primary objective this work is determine whether can blood/lymph...
Abstract During the growth of lymphatic vessels (lymphangiogenesis), endothelial cells (LECs) at growing front sprout by forming filopodia. Those tip are not exposed to circulating lymph, as they lumenized. In contrast, LECs that trail shear stress, become quiescent and remodel into stable vessels. The mechanisms coordinate opposed activities sprouting maturation remain poorly understood. Here we show canonical cell marker Delta-Like 4 (DLL4) promotes lymphangiogenesis enhancing Vascular...
Wnt/β-catenin signaling is necessary for lymphatic vascular patterning and the development of valves. Oscillatory shear stress (OSS) enhances in cultured endothelial cells (LECs) to induce expression lymphedema-associated transcription factors GATA2 FOXC2. However, mechanisms by which OSS regulates FOXC2 are unknown. We show that activates autocrine LECs vitro. Tissue-specific deletion Wntless, required secretion Wnt ligands, reveals smooth muscle complimentary sources ligands regulate vivo....