A5001736006- Bone and Dental Protein Studies
- Cardiovascular Disease and Adiposity
- Angiogenesis and VEGF in Cancer
- Developmental Biology and Gene Regulation
- Cell Adhesion Molecules Research
- Fibroblast Growth Factor Research
- Adipose Tissue and Metabolism
- CRISPR and Genetic Engineering
- Kruppel-like factors research
- dental development and anomalies
- Protease and Inhibitor Mechanisms
- TGF-β signaling in diseases
- Epigenetics and DNA Methylation
- Congenital heart defects research
- MicroRNA in disease regulation
- Cerebrovascular and genetic disorders
- bioluminescence and chemiluminescence research
- Atherosclerosis and Cardiovascular Diseases
- Adipokines, Inflammation, and Metabolic Diseases
- Connective tissue disorders research
- Pluripotent Stem Cells Research
- Cancer-related molecular mechanisms research
- Bone health and treatments
- Kidney Stones and Urolithiasis Treatments
- Urological Disorders and Treatments
University of Maine
2014-2025
MaineHealth
2021-2025
Center for Genomic Science
2024
Maine Medical Center Research Institute
2014-2023
Tufts University
2015-2022
University of Southern Maine
2021-2022
Maine Medical Center
2012-2021
Hospital Pulau Pinang
2017
Center for Molecular Medicine and Immunology
2012-2014
Food Industry Research and Development Institute
2008
Osteopontin (OPN) is an arginine-glycine-aspartate (RGD)- containing glycoprotein encoded by the gene secreted phosphoprotein 1 (spp1). spp1 expressed during embryogenesis, wound healing, and tumorigenesis; however, its in vivo functions are not well understood. Therefore, OPN null mutant mice were generated targeted mutagenesis embryonic stem cells. In mice, embryogenesis occurred normally, fertile. Since shares receptors with vitronectin (VN), we tested for compensation creating lacking...
Osteopontin is an arginine-glycine-aspartate containing acidic glycoprotein postulated to mediate adhesion, migration, and biomineralization in diverse tissues. The mechanisms explaining this multifunctionality are not well understood, although it known that one osteopontin receptor the alpha v beta 3 integrin. In work, we studied human smooth muscle cells varying levels identify additional receptors. We report that, addition 3, both 5 1 Moreover, presence or absence of on cell surface...
Osteopontin (OPN) is a secreted phosphoprotein shown to function in wound healing, inflammation, and tumor progression. Expression of OPN often co-localized with members the matrix metalloproteinase (MMP) family. We report that novel substrate for two MMPs, MMP-3 (stromelysin-1) MMP-7 (matrilysin). Three cleavage sites were identified human OPN, those also cleaved by MMP-7. These include hydrolysis Gly166-Leu167, Ala201-Tyr202 (MMP-3 only), Asp210-Leu211 peptide bonds. Only N-terminal...
Osteopontin is an Arg-Gly-Asp-containing acidic phosphoprotein recently shown to be upregulated in vascular smooth muscle during rat arterial neointima formation and human atherosclerotic plaques. Functional studies showed that osteopontin promoted adhesion of both cultured aortic endothelial cells cells. Adhesion was dose dependent half maximal when solutions containing 7 30 nmol/L were used coat wells for cells, respectively. Smooth adherent spread after 60 minutes, whereas remained round,...
Homologous recombination-based gene targeting using Mus musculus embryonic stem cells has greatly impacted biomedical research. This study presents a powerful new technology for more efficient and less time-consuming in mice injection of zinc-finger nucleases (ZFNs), which generate site-specific double strand breaks, leading to insertions or deletions via DNA repair by the nonhomologous end joining pathway. Three individual genes, multidrug resistant 1a (Mdr1a), jagged 1 (Jag1), notch...
Osteopontin (OPN) is abundantly expressed in human calcified arteries. To examine the role of OPN vascular calcification, mutant mice were crossed with matrix Gla protein (MGP) mice. Mice deficient MGP alone (MGP−/− OPN+/+) showed calcification their arteries as early 2 weeks (wk) after birth (0.33 ± 0.01 mmol/g dry weight), and expression was greatly up-regulated compared wild-types. accumulated adjacent to mineral colocalized surrounding cells media. Cells synthesizing lacked smooth muscle...
Abstract —Osteopontin (OPN), an extracellular matrix protein, is expressed in the myocardium with hypertrophy and failure. We tested hypothesis that OPN plays a role left ventricular (LV) remodeling after myocardial infarction (MI). Accordingly, expression LV structural functional were determined wild-type (WT) knockout (KO) mice 4 weeks MI. Northern analysis showed increased infarcted region, peaking 3 days MI gradually decreasing over next 28 days. In remote LV, was biphasic, peaks at situ...
ABSTRACT. Calcium nephrolithiasis is the most common form of renal stone disease, with calcium oxalate (CaOx) being predominant constituent stones. Current in vitro evidence implicates osteopontin (OPN) as one several macromolecular inhibitors urinary crystallization potentially important actions at stages CaOx crystal formation and retention. To determine importance OPN vivo, hyperoxaluria was induced mice targeted for deletion gene together wild-type control mice. Both groups were given 1%...
Bone morphogenetic protein 8B (BMP8B) is a member of the TGFbeta superfamily growth factors. In mouse, Bmp8b expressed in male germ cells testis and trophoblast placenta, suggesting that it has role spermatogenesis reproduction. To investigate these possibilities, we have generated mice with targeted mutation Bmp8b. Here, show homozygous Bmp8b(tm1blh) mutant males exhibit variable degrees germ-cell deficiency infertility. Detailed analysis reveals two separable defects testes. First, during...
Collagen triple helix repeat containing 1 ( Cthrc1 ) was identified in a screen for differentially expressed sequences balloon-injured versus normal arteries. expression not detectable However, on injury it transiently by fibroblasts of the remodeling adventitia and smooth muscle cells neointima. It also found matrix calcifying human atherosclerotic plaques. CTHRC1 is secreted 28-kDa protein that glycosylated highly conserved from lower chordates to mammals. A short collagen motif with 12...
Adhesive interactions are recognized requirements for cellular proliferation, migration and differentiation during normal morphogenesis as well disease. By differential cloning, osteopontin was identified an adhesive protein upregulated vascular remodeling neointima formation in both rat models human diseases including atherosclerosis restenosis. In functional studies, purified promoted adhesion, focal contact formation, of smooth muscle endothelial cells. Utilizing neutralizing antibodies,...
Abstract The regulatory elements of the Tie2 / Tek promoter are commonly used in mouse models to direct transgene expression endothelial cells. Tunica intima kinase 2 ( ) is also expressed hematopoietic cells, although this has not been fully characterized. We determine lineages adult cells derived from ‐expressing populations using Tie2‐Cre;Rosa26R‐EYFP mice. In mice, analysis bone marrow showed Cre‐mediated recombination 85% population. and spleen, we analyzed subclasses early progenitors,...
Notch and transforming growth factor-beta (TGFbeta) play pivotal roles during vascular development the pathogenesis of disease. The interaction these two pathways is not fully understood. present study utilized primary human smooth muscle cells (SMC) to examine molecular cross-talk between TGFbeta1 signaling on contractile gene expression. Activation using intracellular domain or Jagged1 ligand induced alpha-actin (SM actin), myosin heavy chain, calponin1, expression downstream effectors...
Activation of Notch signaling by Jagged-1 (Jag-1) in vascular smooth muscle cells (VSMC) promotes a differentiated phenotype characterized increased expression contractile proteins. Recent studies show that microRNAs (miR)-143/145 regulates VSMC phenotype. The serum response factor (SRF)/myocardin complex binds to CArG sequences activate miR-143/145 transcription, but no other regulators are known VSMC. Using miR arrays, we found induced following constitutively active Notch1 intracellular...
Infarcted regions of the brain after stroke are segregated from intact by scar tissue comprising both fibrous and glial components. The extent quality scarring is influenced inflammation. matricellular glycoprotein osteopontin (OPN) strongly induced in myeloid cells may contribute to repair ischemic lesions. To elucidate role OPN formation, we photothrombotic infarction, characterized circumscribed cortical infarctions with a well-defined border zone toward parenchyma. cellular source...
ABSTRACT The murine Bmp8a and Bmp8b genes are tightly linked on mouse chromosome 4 have similar expression during reproduction. Previous studies shown that targeted mutagenesis of causes male infertility due to germ cell degeneration. To investigate the function Bmp8a, we inactivated gene by homologous recombination. Heterozygous homozygous mutants reveal normal embryonic postnatal development. Despite high levels in deciduum, mutant females fertility, suggesting is not essential for female...
Abstract Osteopontin is an Arg-Gly-Asp (RGD)–containing acidic glycoprotein postulated to mediate cellular adhesion and migration in a growing number of normal pathological conditions through interaction with integrin molecules. In this report, we have investigated the potential contributions osteopontin one its receptors, α v β 3 integrin, endothelial regenerative processes by using both vivo vitro models. vivo, uninjured rat arterial endothelium had undetectable levels -integrin mRNA situ...