A5071077412- Proteoglycans and glycosaminoglycans research
- Fibroblast Growth Factor Research
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Protease and Inhibitor Mechanisms
- Protein Tyrosine Phosphatases
- Cell Adhesion Molecules Research
- Angiogenesis and VEGF in Cancer
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Wnt/β-catenin signaling in development and cancer
- Carbohydrate Chemistry and Synthesis
- Cancer-related gene regulation
- Platelet Disorders and Treatments
- PI3K/AKT/mTOR signaling in cancer
- T-cell and B-cell Immunology
- Pancreatic function and diabetes
- HER2/EGFR in Cancer Research
- Hippo pathway signaling and YAP/TAZ
- Multiple Myeloma Research and Treatments
- Immunotherapy and Immune Responses
- S100 Proteins and Annexins
- Diabetes Management and Research
- Occupational and environmental lung diseases
- Alzheimer's disease research and treatments
Technion – Israel Institute of Technology
2009-2025
Rambam Health Care Campus
2023
Rappaport Family Institute for Research in the Medical Sciences
2010-2017
Bacterial superantigen toxins bind directly to the dimer interface of CD28, principal co-stimulatory receptor, induce a lethal cytokine storm, and peptides that prevent this binding can suppress lethality.
Heparanase has been implicated in cancer but its contribution to the early stages of development is uncertain. In this study, we utilized nontransformed human MCF10A mammary epithelial cells and two genetic mouse models [Hpa-transgenic (Hpa-Tg) knockout mice] explore heparanase function at tumor development. overexpression resulted significantly enlarged asymmetrical acinar structures, indicating increased cell proliferation decreased organization. This phenotype was enhanced by coexpression...
Heparan sulfate proteoglycans (HSPGs) mediate essential interactions throughout the extracellular matrix (ECM), providing signals that regulate cellular growth and development. Altered HSPG composition during tumorigenesis strongly aids cancer progression. Heparanase (HPSE) is principal enzyme responsible for heparan catabolism markedly up-regulated in aggressive cancers. HPSE overactivity degrades HSPGs within ECM, facilitating metastatic dissemination releasing mitogens drive...
Heparanase 2 (Hpa2, HPSE2) is a close homolog of heparanase. Hpa2, however, lacks intrinsic heparan sulfate (HS)-degrading activity, the hallmark heparanase enzymatic activity. Mutations HPSE2 were identified in patients diagnosed with urofacial syndrome (UFS), rare genetic disorder that exhibits abnormal facial expression and bladder voiding dysfunction, leading to renal damage eventually failure. In order reveal role tissue homeostasis, we established conditional Hpa2-KO mouse....
Heparanase, the heparan sulfate polysaccharide degrading endoglycosidase enzyme, has been correlated with tumor angiogenesis and metastasis therefore become a potential target for anticancer drug development. In this systematic study, sulfation pattern of pendant disaccharide moiety on synthetic glycopolymers was synthetically manipulated to achieve optimal heparanase inhibition. Upon evaluation, glycopolymer 12 repeating units determined be most potent inhibitor (IC50 = 0.10 ± 0.36 nM)....
Mammalian cells express a single functional heparanase, an endoglycosidase that cleaves heparan sulfate and thereby promotes tumor metastasis, angiogenesis, inflammation. Malignant mesothelioma is highly aggressive has poor prognosis because of the lack markers for early diagnosis resistance to conventional therapies. The purpose this study was elucidate mode action biological significance heparanase in test efficacy inhibitors treatment malignancy. involvement investigated by applying mouse...
Expression and activity of heparanase, an endoglycosidase that cleaves heparan sulfate (HS) side chains proteoglycans, is associated with progression poor prognosis many cancers which makes it attractive drug target in cancer therapeutics. In the present work, we report vitro screening a library 150 small molecules scaffold bearing quinolones, oxazines, benzoxazines, isoxazoli(di)nes, pyrimidinones, quinolines, 4-thiazolidinones, thiadiazolo[3,2-a]pyrimidin-5-one,...
Heparanase is an endo‐β‐ d ‐glucuronidase that cleaves heparan sulfate (HS) side chains of proteoglycans. Compelling evidence tie heparanase levels with all steps tumor formation including initiation, growth, metastasis and chemo‐resistance, likely involving augmentation signaling pathways gene transcription. In order to reveal the molecular mechanism(s) underlying protumorigenic properties heparanase, we established inducible (Tet‐on) system in U87 human glioma cells applied array...
The emerging role of heparanase in tumor initiation, growth, metastasis, and chemoresistance is well recognized, encouraging the development inhibitors as anticancer drugs. Unlike function cancer cells, little attention has been given to contributed by cells composing microenvironment. Here, we focused on cross-talk between macrophages, chemotherapy, combined effect progression. Macrophages were markedly activated chemotherapeutics paclitaxel cisplatin, evidenced increased expression...
The endoglycosidase heparanase specifically cleaves the heparan sulfate (HS) side chains on proteoglycans, an activity that has been implicated strongly in tumor metastasis and angiogenesis. Heparanase-2 (Hpa2) is a close homolog of lacks intrinsic HS-degrading but retains capacity to bind HS with high affinity. In head neck cancer patients, Hpa2 expression was markedly elevated, correlating prolonged time disease recurrence inversely cell dissemination regional lymph nodes, suggesting...
Abstract Curative therapy for medulloblastoma and other pediatric embryonal brain tumors has improved, but the outcome still remains poor current treatment causes long-term complications. Malignant infiltrate healthy tissue and, thus despite resection, cells that have already migrated cause rapid tumor regrowth. Heparan sulfate proteoglycans (HSPG), major components of extracellular matrix (ECM), modulate activities a variety proteins. The enzyme degrades HS, heparanase (HPSE), is an...
Tumor cell–platelet interactions are regarded as an initial crucial step in hematogenous metastasis. Platelets protect tumor cells from immune surveillance the blood, mediate vascular arrest, facilitate extravasation, growth, and finally angiogenesis metastatic foci. aggregate platelets bloodstream by activation of plasmatic coagulation cascade direct contact formation. Antimetastatic activities unfractionated or low molecular weight heparin (UFH/LMWH) can undoubtedly be related to...
Heparanase (Hpa1) is expressed by tumor cells and of the microenvironment functions to remodel extracellular matrix (ECM) regulate bioavailability ECM-bound factors that support growth. expression upregulated in human carcinomas, sarcomas, hematological malignancies, correlating with increased metastasis, vascular density, shorter postoperative survival cancer patients, encouraging development heparanase inhibitors as anti-cancer drugs. Among these are heparin/HS mimetics, only...
Heparanase is a mammalian endo-beta-d-glucuronidase that can cleave heparan sulfate side chains, an activity strongly implicated in tumor cell dissemination. The current study aimed to identify and characterize heparanase splice variants. LEADS, Compugen's alternative splicing modeling platform (Compugen, Tel Aviv, Israel), was used search for variants silico; tumor-derived lines (i.e., CAG myeloma) biopsies were utilized validate T5 expression vivo; signaling Src phosphorylation) evaluated...
Heparanase up-regulation was documented in an increasing number of human carcinomas, associated with poor prognosis. The purpose the current study to identify mechanisms responsible for heparanase induction. We provide evidence that expression is regulated at post-transcriptional level by sequences 3' untranslated region (3' UTR) gene. Constructing UTR immediately following cDNA reduces enzymatic activity and protein levels, resulting decreased cellular invasion capacity. further identified...
Cyclic peptides containing unnatural amino acids can modulate Lys-48 ubiquitin chains in cells and animals.