A5006257532- Hippo pathway signaling and YAP/TAZ
- Lymphatic System and Diseases
- Angiogenesis and VEGF in Cancer
- Protein Kinase Regulation and GTPase Signaling
- Sympathectomy and Hyperhidrosis Treatments
- Glaucoma and retinal disorders
- Cellular Mechanics and Interactions
- Cancer Cells and Metastasis
- Cellular transport and secretion
- Wnt/β-catenin signaling in development and cancer
- Dietary Effects on Health
- Corneal Surgery and Treatments
- FOXO transcription factor regulation
- Genetic and Kidney Cyst Diseases
- Retinal Development and Disorders
- TGF-β signaling in diseases
- Hydrogen's biological and therapeutic effects
- Ocular Oncology and Treatments
- Mesenchymal stem cell research
- HIV/AIDS drug development and treatment
- Spinal Dysraphism and Malformations
- HIV Research and Treatment
- Kruppel-like factors research
- Renal Diseases and Glomerulopathies
- Caveolin-1 and cellular processes
Northwestern University
2016-2024
Van Andel Institute
2024
Renal Research Institute
2019-2021
University of South Florida
2020
University of Missouri
2012-2017
Northwestern University
2017
The University of Texas Southwestern Medical Center
2016
Cincinnati Children's Hospital Medical Center
2016
University of Cincinnati
2016
University of North Carolina at Chapel Hill
2016
The Rho family of small GTPases has been shown to be required in endothelial cells (ECs) during blood vessel formation. However, the underlying cellular events controlled by different remain unclear. Here, we assess mechanisms which Cdc42 regulates mammalian vascular morphogenesis and maintenance. In vivo deletion embryonic ECs (Cdc42Tie2KO) results blocked lumen formation tearing, leading lethality mutant embryos E9-10 due failed circulation. Similarly, inducible (Cdc42Cad5KO) at...
The lymphatic vasculature is essential for maintaining interstitial fluid homeostasis, and dysfunctional lymphangiogenesis contributes to various pathological processes, including inflammatory disease tumor metastasis. Mutations in FOXC2 are dominantly associated with late-onset lymphedema; however, the precise role of a closely related factor, FOXC1, system remains largely unknown. Here we identified molecular cascade by which FOXC1 regulate ERK signaling vessel growth. In mice, endothelial...
Vascular tubulogenesis is essential to cardiovascular development. Within initial vascular cords of endothelial cells, apical membranes are established and become cleared cell-cell junctions, thereby allowing continuous central lumens open. Rasip1 (Ras-interacting protein 1) required for junction clearance, as well regulation Rho GTPase (enzyme that hydrolyzes GTP) activity. However, it remains unknown how activities different GTPases coordinated by direct tubulogenesis.The aim this study...
Mutations in the transcription factor FOXC2 are predominately associated with lymphedema. Herein, we demonstrate a key role for related FOXC1, addition to FOXC2, regulating cytoskeletal activity lymphatic valves. FOXC1 is induced by laminar, but not oscillatory, shear and inducible, endothelial-specific deletion impaired postnatal valve maturation mice. However, of Foxc2 degeneration, which exacerbated Foxc1; mutants. knockdown (KD) human endothelial cells increased focal adhesions actin...
Abstract Intestinal ischemia underlies several clinical conditions and can result in the loss of intestinal mucosal barrier. Ischemia‐induced damage to epithelium is repaired by stimulation stem cells (ISCs), paracrine signaling from vascular niche regulates regeneration. Here, we identify FOXC1 FOXC2 as essential regulators regeneration after ischemia–reperfusion (I/R) injury. Vascular endothelial cell (EC)‐ lymphatic EC (LEC)‐specific deletions Foxc1 , Foxc2 or both mice worsen I/R‐induced...
Rilpivirine (RPV) is a second generation nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) that efficiently inhibits HIV-1 resistant to first NNRTIs. Virological failure during therapy with RPV and emtricitabine associated the appearance of E138K M184I mutations in RT. Here we investigate biochemical mechanism RT inhibition resistance RPV. We used two transient kinetics approaches (quench-flow stopped-flow) determine how subunit-specific p66 or p51 affect association dissociation as...
A critical and understudied property of endothelial cells is their ability to form lumens tube networks. Although considerable information has been obtained concerning these issues, including the role Cdc42 Rac1 effectors such as Pak2, Pak4, Par6b, co-regulators integrins, MT1-MMP Par3; many key questions remain that are necessary elucidate molecular signaling requirements for this fundamental process. In work, we identify new small GTPase regulators EC tubulogenesis k-Ras, Rac2 Rap1b act in...
Abstract Angiogenesis, the growth of new blood vessels from pre-existing vasculature, is essential for development organ systems, but transcriptional control angiogenesis remains incompletely understood. Here we show that FOXC1 retinal angiogenesis. Endothelial cell (EC)-specific loss Foxc1 impairs vascular and expression Slc3a2 Slc7a5 , which encode heterodimeric CD98 (LAT1/4F2hc) amino acid transporter regulate intracellular transport acids activation mammalian target rapamycin (mTOR). EC-...
Impaired development and maintenance of Schlemm’s canal (SC) are associated with perturbed aqueous humor outflow intraocular pressure. The angiopoietin (ANGPT)/TIE2 signaling pathway regulates SC maintenance, whereas the molecular mechanisms crosstalk between neural crest (NC)-derived neighboring tissue, trabecular meshwork (TM), poorly understood. Here, we show NC-specific forkhead box ( Fox)c2 deletion in mice results impaired morphogenesis, loss identity, elevated Visible-light optical...
The Rho family of small GTPases has been shown to be required in endothelial cells (ECs) during blood vessel formation. However, the underlying cellular events controlled by different remain unclear. Here, we assess mechanisms which Cdc42 regulates mammalian vascular morphogenesis and maintenance. In vivo deletion embryonic ECs (Cdc42(Tie2KO)) results blocked lumen formation tearing, leading lethality mutant embryos E9-10 due failed circulation. Similarly, inducible (Cdc42(Cad5KO)) at...
Here, we examine known GTPase regulators of vesicle trafficking events to assess whether they affect endothelial cell (EC) lumen and tube formation. We identify novel roles for the small GTPases Rab3A, Rab3B, Rab8A, Rab11A, Rab27A, RalA, RalB caveolin-1 in co-regulating membrane that control EC siRNA suppression individual such as markedly inhibit tubulogenesis, while greater blockade is observed with combinations siRNAs Rab3A Rab8A RalA RalB. These also disrupt very early formation...
Here we examine the question of how endothelial cells (ECs) develop their apical membrane surface domain during lumen and tube formation. We demonstrate marked targeting activated Src kinases to this early late stages process. Immunostaining for phosphotyrosine or phospho-Src reveals staining in intracellular vacuoles initially. This is then followed by vacuole fusion events generate an luminal membrane, which similarly decorated with kinases. Functional blockade completely blocks EC...
4'-phosphopantetheinyl (4'PP) groups are essential co-factors added to target proteins by p hospho antetheinyl transferase (PPTase) enzymes. Although mitochondrial 4'PP-modified have been described for decades, a mitochondrially-localized PPTase has never found in mammals. We discovered that the cytoplasmic mino dipate s emialdehyde d ehydrogenase t ransferase (AASDHPPT) is required respiration and oxidative metabolism. Loss of AASDHPPT results failed 4'-PP modification acyl carrier protein...
Abstract Intestinal ischemia induces mucosal damage while simultaneously activating intestinal stem cells (ISCs), which subsequently regenerate the damaged epithelium. However, whether paracrine factors secreted from vascular endothelial (ECs) - blood and lymphatic ECs (BECs LECs, respectively) – regulate ISC-mediated regeneration have yet to be elucidated. Here, we identify FOXC1 FOXC2 as essential regulators of signaling in small intestine after ischemia-reperfusion (I/R) injury. EC-...