A5061886627- Cell Adhesion Molecules Research
- Wnt/β-catenin signaling in development and cancer
- Atherosclerosis and Cardiovascular Diseases
- Angiogenesis and VEGF in Cancer
- Mitochondrial Function and Pathology
- Cancer-related gene regulation
- Immune cells in cancer
- RNA modifications and cancer
- Protease and Inhibitor Mechanisms
- Nitric Oxide and Endothelin Effects
- Galectins and Cancer Biology
- Transplantation: Methods and Outcomes
- RNA Research and Splicing
- Neuroinflammation and Neurodegeneration Mechanisms
- Folate and B Vitamins Research
- Macrophage Migration Inhibitory Factor
- Ubiquitin and proteasome pathways
- Hippo pathway signaling and YAP/TAZ
- Adipose Tissue and Metabolism
- Cardiomyopathy and Myosin Studies
- Cancer-related Molecular Pathways
- Kruppel-like factors research
- Cancer, Hypoxia, and Metabolism
- Renin-Angiotensin System Studies
- Connective tissue disorders research
Albert Einstein College of Medicine
2016-2025
Montefiore Medical Center
2020-2024
Yeshiva University
2020
St Nicholas Hospital
2012-2017
CVPath Institute
2017
Baylor College of Medicine
2002
Rice University
2002
Brigham and Women's Hospital
1996-2000
Harvard University
1995-2000
Harvard University Press
1996-1999
To examine the role of heme oxygenase (HO)-1 in pathophysiology vascular diseases, we generated mice deficient both HO-1 and apolipoprotein E (HO-1-/-apoE-/-). Despite similar total plasma cholesterol levels response to hypercholesterolemia, HO-1-/-apoE-/- mice, comparison with HO-1+/+apoE-/- had an accelerated more advanced atherosclerotic lesion formation. In addition greater lipid accumulation, these lesions from contained macrophages smooth muscle alpha-actin-positive cells. We further...
Homocysteine is an important and independent risk factor for arteriosclerosis. We showed previously that homocysteine stimulates vascular smooth muscle cell proliferation, a hallmark of show here serum increased DNA synthesis synergistically in both human rat aortic cells (RASMCs). Treatment quiescent RASMCs with 1 mM or 2% calf 36 h cyclin A mRNA levels by 8- 14-fold, respectively, whereas plus 40-fold, indicating synergistic induction mRNA. did not increase the half-life (2.9 h), but it...
Abstract Steroid-resistant nephrotic syndrome (SRNS) causes 15% of chronic kidney disease (CKD). Here we show that recessive mutations in FAT1 cause a distinct renal entity four families with combination SRNS, tubular ectasia, haematuria and facultative neurological involvement. Loss results decreased cell adhesion migration fibroblasts podocytes the is partially reversed by RAC1/CDC42 activator. Podocyte-specific deletion Fat1 mice induces abnormal glomerular filtration barrier development,...
Significance Cardiovascular diseases remain the leading cause of death worldwide, with atherosclerosis being most common source clinical events. Metabolic changes aging associate concurrent increased risk both type 2 diabetes and cardiovascular disease, former further raising latter. The activity a selective autophagy, chaperone-mediated autophagy (CMA), decreases age or upon dietary excesses. Here we study whether reduced CMA increases in mouse models. We have identified that is...
Activated macrophages are critical cellular participants in inflammatory disease states. Transforming growth factor (TGF)-β1 is a with pleiotropic effects including inhibition of immune cell activation. Although the pathway gene activation by TGF-β1 via Smad proteins has recently been elucidated, suppression expression remains poorly understood. We found that Smad1–Smad7, Smad3 alone was able to inhibit markers macrophage (inducible nitric-oxide synthase and matrix metalloproteinase-12)...
Matrix metalloproteinases (MMP) have been identified in vulnerable areas of atherosclerotic plaques and may contribute to plaque instability through extracellular matrix degradation. Human metalloelastase (MMP-12) is a macrophage-specific MMP with broad substrate specificity capable degrading proteins found the atheromas. Despite its potential importance, little known about regulation MMP-12 expression context atherosclerosis. In this study, we report that human peripheral blood-derived...
Lewis-to-F344 rat cardiac allografts develop chronic rejection and arteriosclerotic lesions rich in mononuclear cells (especially macrophages). This study was performed to determine whether cytokine pathways associated with macrophage activation are upregulated hearts undergoing rejection. Gene transcript levels for IFN-gamma, monocyte chemoattractant protein-1 (MCP-1), IL-6 were measured reverse-transcription PCR assays optimized each gene. products confirmed by immunohistology. For all...
Significance Abnormal microglia–neuron interaction is increasingly implicated in neurodevelopmental and neuropsychiatric conditions, such as autism spectrum disorders schizophrenia, well neurodegenerative disorders, Alzheimer’s disease. This study demonstrates that the deletion of microglia-specific protein Iba1, which has long been utilized a selective microglial marker but whose role remained unidentified, results structural functional impairments significantly impact synaptic development...
Canonical Wnt and sphingosine-1-phosphate (S1P) signaling pathways are highly conserved systems that contribute to normal vertebrate development, with key consequences for immune, nervous, cardiovascular system function; despite these functional overlaps, little is known about Wnt/β-catenin-S1P cross-talk. In the vascular system, both Wnt/β-catenin S1P signals affect vessel maturation, stability, barrier function, but information regarding their potential coordination scant. We report an...
To identify genes involved in vascular remodeling, we applied differential mRNA display analysis to the rat carotid artery balloon injury model. One polymerase chain reaction product showing increased expression at days 2 14 after was nearly identical mouse alpha 1 of type VIII collagen, a heterotrimeric short-chain collagen uncertain function expressed by limited number cell types. By Northern analysis, both chains heterotrimer increased: (VIII) almost 4-fold higher than control 7 injury,...
The significance of cadherin superfamily proteins in vascular smooth muscle cell (VSMC) biology is undefined. Here we describe recent studies the Fat1 protocadherin. expression VSMCs increases significantly after arterial injury or growth factor stimulation. knockdown decreases VSMC migration vitro, but surprisingly, enhances cyclin D1 and proliferation. Despite limited similarity to classical cadherins, intracellular domain (Fat1IC) interacts with β-catenin, inhibiting both its nuclear...
Abstract Undifferentiated pleomorphic sarcoma (UPS) is among the most common soft tissue sarcomas (STS) in adults. For decades, little therapeutic progress has been made for STSs, including UPSs. Targeted therapies tumors driven by specific genetic mutations have proven to be more effective than standard chemotherapies. However, molecular pathogenesis of UPSs remains unknown, hindering development targeted Approximately 65% harbor TP53 mutations, but somatic mutation Trp53 alone insufficient...
Abstract Undifferentiated pleomorphic sarcoma (UPS) is among the most common soft tissue sarcomas (STS) in adults. For decades, little therapeutic progress has been made for STSs, including UPSs. Targeted therapies tumors driven by specific genetic mutations have proven to be more effective than standard chemotherapies. However, molecular pathogenesis of UPSs remains unknown, hindering development targeted Approximately 65% harbor TP53 mutations, but somatic mutation Trp53 alone insufficient...
Although several cytokines and growth factors have been shown to regulate vascular endothelial factor (VEGF) production, little is known about how VEGF may that mitogenic chemotactic actions on mesenchymal cells (which are involved in the maturation of angiogenic process). We investigated effect heparin-binding epidermal factor-like (HB-EGF) expression human umbilical vein cells. HB-EGF mRNA was induced by 8-fold after 2 h stimulation, it returned base line within 6 h. did not alter...
Abstract Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary formation remain ill-defined. Here we identify an angiogenic cell population for in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis, these cells generate mature arteries. The NOTCH modulator POFUT1 critically regulates this axis. inactivation disrupts events and results excessive proliferation plexus formation, leading to anomalous...
Background and aimsAllograft inflammatory factor-1 (AIF1) has been characterized as a pro-inflammatory molecule expressed primarily in the monocyte/macrophage (MP) lineage positively associated with various forms of vascular disease, including atherosclerosis. Studies AIF1 atherosclerosis have relied on mouse models which was overexpressed either myeloid or smooth muscle cells, resulting increased atherosclerotic plaque burden. How physiologic expression contributes to MP biology...
Recent studies implicate macrophages in regulation of thermogenic, sympathetic neuron-mediated norepinephrine (NE) signaling adipose tissues, but understanding such non-classical macrophage activities is incomplete. Here we show that male mice lacking the allograft inflammatory factor-1 (AIF1) protein resist high fat diet (HFD)-induced obesity and hyperglycemia. We link this phenotype to higher NE levels stem from decreased monoamine oxidase A (MAOA) expression clearance by AIF1-deficient...
Abstract —Proteins of the LIM family are critical regulators development and differentiation in various cell types. We have described cloning cysteine-rich protein 2/smooth muscle (CRP2/SmLIM), a LIM-only expressed differentiated vascular smooth cells. As first step toward understanding potential functions CRP2/SmLIM, we analyzed its expression after gastrulation developing mice compared CRP2/SmLIM with that other 2 members CRP subclass, CRP1 CRP3/MLP. In situ hybridization whole-mount...