A5069459067- Proteoglycans and glycosaminoglycans research
- Cell Adhesion Molecules Research
- Protease and Inhibitor Mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- Fibroblast Growth Factor Research
- Nanoparticle-Based Drug Delivery
- Nanoplatforms for cancer theranostics
- Advanced biosensing and bioanalysis techniques
- Cancer-related Molecular Pathways
- Sarcoma Diagnosis and Treatment
- CAR-T cell therapy research
- Platelet Disorders and Treatments
- Corneal Surgery and Treatments
- Virus-based gene therapy research
- Thyroid Cancer Diagnosis and Treatment
- Gold and Silver Nanoparticles Synthesis and Applications
- Angiogenesis and VEGF in Cancer
- Cancer, Hypoxia, and Metabolism
- Connexins and lens biology
- Wnt/β-catenin signaling in development and cancer
- Kruppel-like factors research
- Bone health and treatments
- Monoclonal and Polyclonal Antibodies Research
- Melanoma and MAPK Pathways
- Biochemical and Structural Characterization
Touro College
2020
Baruch College
2020
Kettering University
2010-2017
Icahn School of Medicine at Mount Sinai
2000-2010
Memorial Sloan Kettering Cancer Center
2008-2010
Hebrew University of Jerusalem
1993-2002
Hadassah Academic College
1990-2001
Max Planck Institute of Biochemistry
1992
Hadassah Medical Center
1992
Weizmann Institute of Science
1989
Nanoparticle-based materials, such as drug delivery vehicles and diagnostic probes, currently under evaluation in oncology clinical trials are largely not tumor selective. To be clinically successful, the next generation of nanoparticle agents should selective, nontoxic, exhibit favorable targeting clearance profiles. Developing probes meeting these criteria is challenging, requiring comprehensive vivo evaluations. Here, we describe our full characterization an approximately 7-nm diameter...
Cell lines derived from human cancers provide critical tools to study disease mechanisms and develop novel therapies. Recent reports indicate that up 36% of cell are cross- contaminated.We evaluated 40 reported thyroid cancer-derived using short tandem repeat single nucleotide polymorphism array analysis.Only 23 tested have unique genetic profiles. The following groups likely derivatives the same line: BHP5-16, BHP17-10, BHP14-9, NPA87; BHP2-7, BHP10-3, BHP7-13, TPC1; KAT5, KAT10, KAT4,...
Sprouty was genetically identified as an antagonist of fibroblast growth factor signaling during tracheal branching in Drosophila. In this study, we provide a functional characterization mammalian Sprouty1 and Sprouty2. Sprouty2 inhibited events downstream multiple receptor tyrosine kinases regulated both cell proliferation differentiation. Using NIH3T3 lines conditionally expressing or Sprouty2, found that these proteins specifically inhibit the Ras/Raf/MAP kinase pathway by preventing Ras...
Esterolytically inactive diisopropyl fluorophosphate-conjugated thrombin (DIP-alpha-thrombin) stimulated 3H-thymidine incorporation and proliferation of growth-arrested vascular smooth muscle cells (SMCs), similar to native alpha-thrombin. Half-maximal mitogenic response SMCs was obtained at 1 nM specifically blocked by the leech-derived, high-affinity inhibitor, hirudin. Native a variety species that were chemically modified alter procoagulant or esterolytic functions found induce extent....
Context: Mutually exclusive mutations of RET, RAS, or BRAF are present in about 70% papillary thyroid carcinomas, whereas only the latter two seen poorly differentiated and anaplastic cancers. Although signal output common to these oncoproteins is ERK, a recent report showed that consistently predicted responsiveness MAPK kinase (MEK) inhibitors. Objectives: Here we investigated whether sensitivity MEK inhibition was determined by oncogene status 13 human cancer cell lines: four with...
Breast cancer 1, early onset (BRCA1) expression is often reduced in sporadic breast tumors, even the absence of BRCA1 genetic modifications, but molecular basis for this unknown. In study, we identified homeobox A9 (HOXA9) as a gene frequently downregulated human cancers and tumor cell lines noted that HOXA9 transcript levels associated with aggression, metastasis, patient mortality. Experiments revealed loss promoted mammary epithelial growth survival perturbed tissue morphogenesis....
Although a large body of literature exists on the potential use nanoparticles for medical applications, number probes translated into human clinical trials is remarkably small. A major challenge particle probe development and their translation elucidation safety profiles associated with structural complexity, not only in terms size distribution heterogeneities composition but also effects biological activities relationship between structure pharmacokinetics. Here, we report synthesis,...
Fibroblasts and myofibroblasts both participate in wound healing. Transforming growth factor beta (TGFbeta) induces fibroblasts to differentiate into myofibroblasts, whereas fibroblast heparin (FGF/h) induce "de-differentiate" fibroblasts. TGFbeta expression of smooth muscle alpha actin (SMalphaA) incorporation stress fibers, a phenotype differentiated myofibroblasts. Additionally, the fibronectin integrins. Fibronectin-generated signals contribute TGFbeta-mediated myofibroblast...
The poor prognosis associated with malignant melanoma has not changed substantially over the past 30 years. Targeted molecular therapies, such as immunotherapy, have shown promise but suffer from resistance and off-target toxicities, underscoring need for alternative therapeutic strategies that can be used in combination existing protocols. Moreover, peptides targeting melanoma-specific markers, like melanocortin-1 receptor (MC1-R), imaging therapy exhibit high renal uptake limits clinical...
BRCA1 is a tumor suppressor gene mutated in cases of hereditary breast and ovarian cancer. protein involved apoptosis growth/tumor suppression. In this study, we present evidence that p65/RelA, one the two subunits transcription factor NF-kappaB, binds to protein. Treatment 293T cells with cytokine necrosis factor-alpha induces an interaction between endogenous p65/RelA BRCA1. GST-protein affinity assay experiments reveal Rel homology domain subunit NF-kappaB interacts multiple sites within...
Dasatinib, a new-generation Src and platelet-derived growth factor receptor (PDGFR) inhibitor, is currently under evaluation in high-grade glioma clinical trials. To achieve optimum physicochemical and/or biologic properties, alternative drug delivery vehicles may be needed. We used novel fluorinated dasatinib derivative (F-SKI249380), combination with nanocarrier metabolic imaging tools (microPET) to evaluate uptake B (PDGFB)-driven genetically engineered mouse model (GEMM) of glioma....
BRCA1, a breast and ovarian cancer susceptibility gene, encodes 220-kDa protein whose precise biochemical function remains unclear. BRCA1 contains an N-terminal RING finger that mediates protein-protein interaction. The C-terminal domain of (BRCT) can activate transcription interacts with RNA polymerase holoenzyme. Using the yeast two-hybrid system, we identified interaction between ATF1, member cAMP response element-binding protein/activating factor (CREB/ATF) family. We demonstrate ATF1...
Cellular and molecular‐level interactions of nanoparticles with biological systems are a rapidly evolving field requiring an improved understanding endocytic trafficking as the principal driver regulator signaling events cellular responses. An these processes is vital to nanomedicine applications. Studies investigating complex interplay their relationship targeted exploiting pathways notably lacking. It known that integrins traffic through endosomal pathway participate in diverse roles...
Proliferation of bovine aortic smooth muscle cells (SMCs) induced by thrombin, basic fibroblast growth factor, or serum is inhibited anionic, nonsulfated aromatic compounds that mimic many the effects heparin. Among these are aurintricarboxylic acid (ATA) and a newly synthesized polymer 4-hydroxyphenoxy acetic (compound RG-13577). Iodinated- 14C-labeled compound RG-13577 binds to cultured SMCs in highly specific saturable manner. Scatchard analysis binding data revealed presence an estimated...
To explore the roles of ZO-1 in corneal fibroblasts and myofibroblasts a model wounding.Antibodies were used to identify cultured rabbit by immunocytochemistry, Western blot analysis, immunoprecipitation. For colocalization studies, antibodies beta-catenin, cadherins, connexins, integrins, alpha-actinin, cortactin used. G- F-actin identified DNase rhodamine phalloidin, respectively. study localization during cell migration, confluent subjected scrape-wounding evaluated immunocytochemistry.As...
Background: The purpose of our study was to find a novel targeted imaging and drug delivery vehicle for inflammatory bowel disease (IBD). IBD is common troublesome that still lacks effective therapy options. As an attempt improve the treatment, we tested αMSH targeting nanoliposomes sites. αMSH, endogenous tridecapeptide, binds melanocortin-1 receptor (MC1-R) has anti-inflammatory immunomodulating effects. MC1-R found on macrophages, neutrophils renal tubule system. We formulated liposomal...
Abstract A series of nine synthetic polyaromatic compounds were synthesized by polymerization aromatic ring monomers with formaldehyde, which yield substantially ordered backbones different functional anionic groups (hydroxyl and carboxyl) on the phenol ring. These tested for their heparin‐mimicking activity: (1) inhibition heparanase activity; (2) SMC proliferation; (3) release bFGF from ECM. We demonstrate that have two hydroxyl para ortho to carboxylic group a at distance carbons inhibit...
purpose. Within the multidomain structure of ZO-1 are motifs responsible for ZO-1's localization to intercellular junctions and its newly demonstrated leading edge lamellipodia in corneal fibroblasts. Since also has two nuclear signals, this study was undertaken determine whether stimuli associated with wounding would induce translocation methods. Immunocytochemistry immunoblot analysis were used localize endogenous exogenous cytoplasmic sites fibroblasts 293T fibroblasts, without myc-ZO-1...
A synthetic heparin-mimicking polyaromatic anionic compound RG-13577 (polymer of 4-hydroxyphenoxy acetic acid and formaldehyde ammonium salt, Mr∼5800) exhibits specific binding to vascular smooth muscle cells (SMCs) inhibits their proliferative response growth promoting factors. Receptor 14C-RG-13577 was efficiently competed by apolipoprotein E3 (apoE), lactoferrin, the LRP (LDL receptor-related protein) receptor associated 39 kDa protein (RAP). Unlike cell surface apoE, SMCs not affected...