A5040250816- Tuberous Sclerosis Complex Research
- Protease and Inhibitor Mechanisms
- Peptidase Inhibition and Analysis
- Cell Adhesion Molecules Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Neonatal Respiratory Health Research
- Sarcoma Diagnosis and Treatment
- Pulmonary Hypertension Research and Treatments
- Asthma and respiratory diseases
- Tumors and Oncological Cases
- Vascular Tumors and Angiosarcomas
- Renal and related cancers
- HER2/EGFR in Cancer Research
- Cancer Diagnosis and Treatment
- Respiratory Support and Mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- Adipose Tissue and Metabolism
- Pituitary Gland Disorders and Treatments
- Osteoarthritis Treatment and Mechanisms
- Neuroendocrine Tumor Research Advances
- Ion channel regulation and function
- Tuberculosis Research and Epidemiology
- Wnt/β-catenin signaling in development and cancer
- Signaling Pathways in Disease
International University of Health and Welfare
2019-2024
Columbia University
2010-2023
Keio University
2002-2017
New York University
2011-2017
New York Hospital Queens
2015
Columbia University Irving Medical Center
2015
NewYork–Presbyterian Hospital
2015
Max Planck Institute for Heart and Lung Research
2015
Nitobe Memorial Nakano General Hospital
2010
Cardiovascular Research Center
2008
Vascular endothelial growth factor (VEGF) is a strong angiogenic mitogen and plays important roles in angiogenesis under various pathophysiological conditions. The vivo activity of secreted VEGF may be regulated by extracellular inhibitors, because it also produced avascular tissues such as the cartilage. To seek binding inhibitors against VEGF, we screened chondrocyte cDNA library yeast two-hybrid system using VEGF165 bait identified connective tissue (CTGF) candidate. complex formation...
Mycobacterium tuberculosis can cause lung tissue damage to spread, but the mechanisms driving this immunopathology are poorly understood. The breakdown of matrix involves MMPs, which have a unique ability degrade fibrillar collagens at neutral pH. To determine whether MMPs play role in (TB), we profiled and their inhibitors, inhibitor metalloproteinases (TIMPs), sputum bronchoalveolar lavage fluid from patients with TB symptomatic controls. MMP-1 concentrations were significantly increased...
A central tenet of tuberculosis pathogenesis is that caseous necrosis leads to extracellular matrix destruction and bacterial transmission. We reconsider the underlying mechanism pathology demonstrate collagen may be a critical initial event, causing as opposed resulting from it. In human granulomas, regions map areas necrosis. mice, transgenic expression metalloproteinase 1 causes necrosis, pathological hallmark tuberculosis. Collagen principal difference between humanised mice wild-type...
ADAMs (a disintegrin and metalloproteinases) are multifunctional molecules involved in cell-cell fusion, cell adhesion, membrane protein shedding, proteolysis. In the present study, we examined mRNA expression of 13 different ADAM species with putative metalloproteinase activity human astrocytic tumors, nonneoplastic brain tissues, other intracranial tumors by reverse transcriptase-polymerase chain reaction, found that prototype membrane-anchored ADAM12 (ADAM12m) is predominantly expressed...
A disintegrin and metalloproteinases (ADAMs) are involved in various biological events including cell adhesion, fusion, membrane protein shedding, proteolysis. In the present study, our reverse transcription-PCR analysis showed that among 12 different ADAM species with a putative metalloproteinase motif, prototype membrane-anchored ADAM28m secreted-type ADAM28s selectively expressed human breast carcinoma tissues. By real-time quantitative PCR, their expression levels were significantly...
A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)1, 4, 5, 8, 9 15, members of the ADAMTS gene family, have ability to degrade a major cartilage proteoglycan, aggrecan, at specific sites, thus are called ‘aggrecanases’. The expression these species was examined in human osteoarthritic articular on reverse transcription–polymerase chain reaction. results demonstrated predominant ADAMTS4 cartilage, while ADAMTS5 constitutively expressed normal cartilage. ADAMTS9 mainly...
RationaleIdiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by excessive deposition of extracellular matrix (ECM). ObjectivesWe investigated the regulation metalloproteinases (MMPs) and their inhibitors (TIMPs) in lung fibrosis. MethodsMMP TIMP expression, collagenolytic activity collagen content was assessed IPF (n=16) versus donor (n=6) homogenates accomplished in-situ-zymography for gelatinolytic activities, combined with MMP antigen detection. Role MMP13 employing...
Matrix metalloproteinase-2 (MMP-2) is a stroma-derived MMP belonging to the type IV collagenase family. It believed mediate tumor cell behavior by degrading deposits of collagen, major component basement membrane. The membrane 1-MMP (MT1-MMP) highly potent activator MMP-2 and expressed in many stromal cells. However, roles played progression vivo remain poorly understood. We established colon epithelial line from an Mt1-mmp(-/-) mouse strain transfected these cells with inducible expression...
Idiopathic pulmonary fibrosis (IPF) is a chronically progressive interstitial lung disease of unknown etiology. Previously, we have demonstrated the selective upregulation macrophage-derived chemokine CCL22 and thymus activation-regulated CCL17 among chemokines, in rat model radiation pneumonitis/pulmonary preliminarily observed an increase bronchoalveolar (BAL) fluid levels IPF patients.We examined expression CCR4, specific receptor for CCL17, lavage cells, as well to elucidate their...
Disruption of the sarcolemma-associated dystrophin-glycoprotein complex underlies multiple forms muscular dystrophy, including Duchenne dystrophy and sarcoglycanopathies. A hallmark these disorders is muscle weakness. In a murine model mdx mice, cysteine-nitrosylation calcium release channel/ryanodine receptor type 1 (RyR1) on skeletal sarcoplasmic reticulum causes depletion stabilizing subunit calstabin1 (FKBP12) from RyR1 macromolecular complex. This results in reticular leak via defective...
Abstract Context.—Idiopathic pulmonary fibrosis (IPF) is characterized by diffuse interstitial inflammation and fibroblast proliferation with accelerated remodeling of extracellular matrix, which r...
Abstract Context.—Idiopathic pulmonary fibrosis (IPF) is characterized by diffuse interstitial inflammation and fibroblast proliferation with accelerated remodeling of extracellular matrix, which result in irreversible destruction the lung's architecture. Objective.—To elucidate production levels, tissue localization, activation matrix metalloproteinase 7 (MMP-7) lungs patients IPF. Design.—Bronchoalveolar lavage analysis was performed 17 IPF 6 healthy volunteers. Levels MMP-7 blood were...
The Wnt/β-catenin signaling pathway plays a central role during cardiac development and has been implicated in remodeling aging. However, the of Wnt modulators this process is unknown. In study, we examined inhibitor secreted frizzled-related protein-1 (sFRP-1) aged wild-type sFRP-1-deficient mice.sFRP-1 gene deletion mice were grossly normal with no difference mortality but developed abnormal structure dysfunction progressive age. Ventricular dilation hypertrophy addition to deterioration...
Enhancement of contractile force (inotropy) occurs in skeletal muscle following neuroendocrine release catecholamines and activation β-adrenergic receptors. Despite extensive study, the molecular mechanism underlying inotropic response is not well understood. Here we show that phosphorylation a single serine residue (S2844) sarcoplasmic reticulum (SR) Ca(2+) channel/ryanodine receptor type 1 (RyR1) by protein kinase A (PKA) critical for inotropy. Treating fast twitch from wild-type mice with...
ADAM (a disintegrin and metalloproteinases) are a recently discovered gene family of proteins with sequence similarity to the reprolysin snake venom metalloproteinases, about one-third members have catalytic site consensus in their metalloproteinase domains. We screened mRNA expression 11 different species putative activity human non-small cell lung carcinomas by RT-PCR, found that prototype membrane-anchored ADAM28 (ADAM28m) secreted (ADAM28s) predominantly expressed carcinoma tissues....
Membrane-type 1 matrix metalloproteinase (MT1-MMP/MMP-14) is an enzyme that promotes tumor cell invasion in tissues. Although the proteolytic activity of MT1-MMP indispensable for invasion, it also regulated by functions cytoplasmic tail. In this study we obtained a new human gene whose product binds to tail sequence yeast. The product, MTCBP-1, 19-kDa protein belongs newly proposed Cupin superfamily composed proteins with diverse functions. MTCBP-1 expressed cells formed complex and...
To investigate the anti-inflammatory and anti-angiogenic effects of telmisartan, an angiotensin II type 1 receptor (AT1-R) antagonist, on ischemia-induced retinal neovascularization.C57BL/6 neonatal mice were reared in 80% concentration oxygen from postnatal day (P)7 to P12, followed by room-air breathing until P17, induce ischemia-initiated neovascularization (i.e., a murine model ischemic retinopathy). Tissue localization AT1-R was examined immunohistochemistry for wholemounts human...