A5021766049- Cell Adhesion Molecules Research
- Angiogenesis and VEGF in Cancer
- Cancer, Hypoxia, and Metabolism
- Wnt/β-catenin signaling in development and cancer
- Cellular Mechanics and Interactions
- Caveolin-1 and cellular processes
- Pluripotent Stem Cells Research
- Kruppel-like factors research
- Renal and related cancers
- Cancer-related gene regulation
- Neonatal Respiratory Health Research
- Atherosclerosis and Cardiovascular Diseases
- Protease and Inhibitor Mechanisms
- Mesenchymal stem cell research
- Cancer, Lipids, and Metabolism
- Sphingolipid Metabolism and Signaling
- Protein Kinase Regulation and GTPase Signaling
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Signaling Pathways in Disease
- RNA modifications and cancer
- Nitric Oxide and Endothelin Effects
- NF-κB Signaling Pathways
- Immune cells in cancer
- Cancer-related molecular mechanisms research
University of Illinois Chicago
2015-2025
University of Illinois Urbana-Champaign
2007-2025
GTx (United States)
2022
Illinois College
2009-2019
University of Chicago
2009
Texas A&M University System
2003-2005
Texas A&M University
2005
Texas Medical Center
2003-2005
Memorial Sloan Kettering Cancer Center
1997-2003
Matrix Biology Institute
2003
We provide evidence that a class of integrins combines with the adaptor Shc and thereby Grb2. Coimmunoprecipitation mutagenesis experiments indicate recruitment is specified by extracellular or transmembrane domain integrin α subunit suggest this process mediated caveolin. Mutagenesis dominant-negative inhibition studies reveal necessary sufficient for activation MAP kinase pathway in response to ligation. Mitogens Shc-activating cooperate promote transcription from Fos serum element transit...
Activation of integrins upon binding to extracellular matrix proteins is believed be a crucial step for the regulation cell survival and proliferation. We have used integrin α1-null mice investigate role this collagen receptor in growth vivo. α1-deficient animals, which are viable fertile, hypocellular dermis deficiency dermal fibroblast proliferation as embryos. In vitro analysis embryonic fibroblasts has revealed that their rate markedly reduced when plated on collagenous substrata,...
It has been well established that the tumor microenvironment can promote cell adaptation and survival. However, mechanisms influence malignant progression have not clearly elucidated. We previously demonstrated cells cultured under hypoxic/anoxic conditions transformed in hypoxic areas of tumors activate a translational control program known as integrated stress response (ISR). Here, we show derived from K-Ras-transformed Perk(-/-) mouse embryonic fibroblasts (MEFs) are smaller exhibit less...
The extracellular matrix exerts a stringent control on the proliferation of normal cells, suggesting existence mitogenic signaling pathway activated by integrins, but not significantly growth factor receptors. Herein, we provide evidence that integrins cause significant and protracted activation Jun NH2-terminal kinase (JNK), while several factors more modest or no this enzyme. Integrin-mediated stimulation JNK required association focal adhesion (FAK) with Src p130CAS, phosphorylation...
Recent investigations have focused on characterizing the molecular components of podocyte intercellular junction, because several these components, including Nephrin, are functionally necessary for development normal structure and filter integrity. Accumulating evidence suggests that Nephrin-associated protein complex is a signaling nexus. As such, Nephrin-dependent might be mediated in part through Nephrin phosphorylation. Described biochemical mouse genetics experiments demonstrating...
Bone marrow (BM) is the major reservoir for endothelial progenitor cells (EPCs). Postnatal neovascularization depends on not only angiogenesis but also vasculogenesis, which mediated through mobilization of EPCs from BM and their recruitment to ischemic sites. Reactive oxygen species (ROS) derived Nox2-based NADPH oxidase play an important role in postnatal neovascularization; however, EPC function unknown. Here we show that hindlimb ischemia mice significantly increases Nox2 expression ROS...
Vascular endothelial barrier dysfunction underlies diseases such as acute respiratory distress syndrome (ARDS), characterized by edema and inflammatory cell infiltration. The transcription factor HIF2α is highly expressed in vascular cells (ECs) may regulate function. Here, we analyzed promoter sequences of genes encoding proteins that adherens junction (AJ) integrity determined protein tyrosine phosphatase (VE-PTP) a target. HIF2α-induced VE-PTP expression enhanced dephosphorylation...
It has been proposed that integrins activate ERK through the adaptor protein Shc independently of focal adhesion kinase (FAK) or FAK acting on multiple target effectors, including Shc. We show disruption actin cytoskeleton by cytochalasin D causes a complete inhibition but does not inhibit signaling and activation ERK. have then generated primary fibroblasts carrying targeted deletion segment β<sub>1</sub> subunit cytoplasmic domain required for FAK. Analysis these cells indicates is...
Vascular endothelial (VE)-cadherin localized at adherens junctions (AJs) regulates barrier function. Because WNT (wingless) signaling-induced activation of the transcription factor Krüppel-like (KLF)4 may have an important role in mediating expression VE-cadherin and AJ integrity, we studied function KLF4 regulating control function.The goal this study was to determine transcriptional function.Expression analysis, microscopy, chromatin immunoprecipitation, electrophoretic mobility shift...
The vascular endothelial growth factor-A (VEGF-A)-VEGFR2 pathway drives tumor vascularization by activating proangiogenic signaling in cells (ECs). Here, we show that EC-sphingosine-1-phosphate receptor 1 (S1PR1) amplifies VEGFR2-mediated angiogenic to enhance growth. We cancer induce S1PR1 activity ECs, and thereby, conditional deletion of ECs (EC-S1pr1−/− mice) impairs Mechanistically, engages the heterotrimeric G-protein Gi, which VEGF-VEGFR2 due an increase tyrosine kinase c-Abl1....
The streptococcal collagen-like proteins Scl1 and Scl2 are prokaryotic members of a large protein family with domains containing the repeating amino acid sequence (Gly-Xaa-Yaa)(n) that form triple-helical structure. Here, we test hypothesis Scl variant might interact mammalian collagen-binding integrins. We show recombinant p176 promotes adhesion spreading human lung fibroblast cells through an alpha2beta1 integrin-mediated interaction as shown in cell inhibition assays using...
Although trafficking of newly synthetized VEGFR2 to the plasma membrane is a key determinant angiogenesis, molecular mechanisms Golgi are unknown. Here we identified role kinesin family plus-end motor KIF13B in delivering cargo from endothelial cell surface. was shown interact directly with on microtubules. We also observed that over-expression binding domain interacting inhibited VEGF-induced capillary tube formation. depletion prevented VEGF-mediated migration, formation, and...
Endothelial biomechanics is emerging as a key factor in endothelial function. Here, we address the mechanisms of stiffening induced by oxidized LDL (oxLDL) and investigate role oxLDL lumen formation. We show that oxLDL-induced mediated CD36-dependent activation RhoA its downstream target, Rho kinase (ROCK), via inhibition myosin light-chain phosphatase (MLCP) (MLC)2 phosphorylation. The LC-MS/MS analysis identifies 7-ketocholesterol (7KC) major oxysterol oxLDL. Similarly to oxLDL, 7KC...
Identification of the genes and pathways associated with activation endothelial cells (ECs) could help uncover role ECs in wound healing, vascular permeability, blood brain barrier function, angiogenesis, diabetic retinopathy, atherosclerosis, psoriasis, growth solid tumors. Herein, we embedded 3D type I collagen gel, left unstimulated or stimulated VEGF165, subjected to suppression subtractive hybridization followed by differential display (SSHDD). Gene fragments obtained from SSHDD were...
Understanding epigenetic mechanisms regulating embryonic stem cell (ESC) differentiation to endothelial cells may lead increased efficiency of generation vessel wall needed for vascular engineering. Here we demonstrated that the histone demethylases KDM4A and KDM4C played an indispensable but independent role in mediating expression fetal liver kinase (Flk)1 VE-cadherin, respectively, thereby transition mouse ESCs (mESCs) cells. was shown bind histones associated with Flk1 promoter...