A5074336094- Proteoglycans and glycosaminoglycans research
- Protease and Inhibitor Mechanisms
- Microbial metabolism and enzyme function
- Peptidase Inhibition and Analysis
- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- Developmental Biology and Gene Regulation
- Connective tissue disorders research
- Genomics and Chromatin Dynamics
- Tissue Engineering and Regenerative Medicine
- Muscle Physiology and Disorders
- Fibroblast Growth Factor Research
- Congenital heart defects research
- Tendon Structure and Treatment
- Congenital limb and hand anomalies
- Cancer Cells and Metastasis
- Wnt/β-catenin signaling in development and cancer
- Renal cell carcinoma treatment
- Cancer Immunotherapy and Biomarkers
- Corneal Surgery and Treatments
- Hippo pathway signaling and YAP/TAZ
- Protein Tyrosine Phosphatases
- Intracranial Aneurysms: Treatment and Complications
- Biochemical Acid Research Studies
- RNA Research and Splicing
Technion – Israel Institute of Technology
2011-2024
Rappaport Family Institute for Research in the Medical Sciences
2023
Génétique et biologie du développement
2023
The Francis Crick Institute
2007
Hebrew University of Jerusalem
2001-2004
Abstract Monoclonal antibodies (mAbs) hold promise in treating Parkinson's disease (PD), although poor delivery to the brain hinders their therapeutic application. In current study, it is demonstrated that brain‐targeted liposomes (BTL) enhance of mAbs across blood‐brain‐barrier (BBB) and into neurons, thereby allowing intracellular extracellular treatment PD brain. BTL are decorated with transferrin improve targeting through overexpressed transferrin‐receptors on BBB during PD. loaded...
Proper functioning of the musculoskeletal system requires precise integration bones, muscles, and tendons. Complex morphogenetic events ensure that these elements are linked together in appropriate three-dimensional configuration. It has been difficult, however, to tease apart mechanisms regulate tissue morphogenesis. We find deletion Tbx5 forelimbs (or Tbx4 hindlimbs) specifically affects muscle tendon patterning without disrupting skeletal development, thus suggesting distinct cues...
Vertebrate muscles and tendons are derived from distinct embryonic origins yet they must interact in order to facilitate muscle contraction body movements. How robust tendon junctions (MTJs) form be able withstand forces is still not understood. Using techniques at a single cell resolution we reexamine the classical view of identities for tissues composing musculoskeletal system. We identify fibroblasts that have switched on myogenic program demonstrate these dual identity cells fuse into...
Abstract Metastasis is the main cause of cancer-related mortality. Despite intense efforts to understand mechanisms underlying metastatic process, treatment cancer still challenging. Here we describe a chemotherapy-induced, host-mediated mechanism that promotes remodeling extracellular matrix (ECM), ultimately facilitating cell seeding and metastasis. Paclitaxel (PTX) chemotherapy enhanced rapid ECM mechanostructural changes in lungs tumor-free mice, protein expression activity enzyme lysyl...
Muscle is an integrated tissue composed of distinct cell types and extracellular matrix. While much emphasis has been placed on the factors required for specification cells that comprise muscle, little known about crosstalk between them enables development a patterned functional tissue. We find in mice deletion lysyl oxidase (Lox), enzyme regulating collagen maturation organization, uncouples balance amount myofibers muscle connective (MCT). show Lox secreted from attenuates TGFβ signaling,...
Mutations in key transcription factors SOX2 and P63 were linked with developmental defects postnatal abnormalities such as corneal opacification, neovascularization, blindness. The latter phenotypes suggest that may be involved epithelial regeneration. Although has been shown to a regulator of limbal stem cells, the expression pattern function adult cornea remained unclear. Here, we show regulates control stem/progenitor cell function. co-expressed compartments murine vivo undifferentiated...
The cell fate decisions of stem cells (SCs) largely depend on signals from their microenvironment (niche). However, very little is known about how biochemical niche cues control behavior in vivo. To address this question, we focused the corneal epithelial SC model which niche, as limbus, spatially segregated differentiation compartment. We report that unique biomechanical property limbus supports nuclear localization and function Yes-associated protein (YAP), a putative mediator...
Tbx5 is essential for initiation of the forelimb, and its deletion in mice results failure forelimb formation. Misexpression dominant-negative forms limb truncations,suggesting also required outgrowth. Here we show that expressed throughout mesenchyme progenitors cartilage, tendon muscle. Using a tamoxifeninducible Cre transgenic line, map time frame during which development. We subsequent to does not impair Furthermore, distinguish two distinct phases development: Tbx5-dependent phase,...
In this minireview, we briefly revisit the Drosophila Notch and epidermal growth factor receptor pathways, relate to relationship between them. We then mainly focus on involvement of Groucho (Gro)/TLE, a global developmental corepressor, in these pathways. particular, discuss Gro/TLE's role at junction two signal transduction cascades.
Drosophila Groucho (Gro) is a member of family metazoan corepressors with widespread roles in development. Previous studies indicated that conserved domain Gro, termed the Q domain, was required for repression cultured cells and mediated homotetramerization. Evidence presented here suggests contains two coiled-coil motifs oligomerization vivo. Mutagenesis putative hydrophobic faces these motifs, but not hydrophilic faces, prevents formation both tetramers higher order oligomers. context...
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...
Fibronectin fibrillogenesis and mechanosensing both depend on integrin-mediated force transmission to the extracellular matrix. However, is in itself dependent fibrillogenesis, fibronectin fibrils are found soft embryos where high forces cannot be applied, suggesting that sole initiator of fibrillogenesis. Here, we identify a nucleation step prior transmission, driven by oxidation mediated lysyl oxidase enzyme family members. This induces clustering, which promotes early adhesion, alters...
Brain-Targeted Liposomes In article number 2304654, Avi Schroeder and co-workers describe a targeted nanotechnology drug delivery system for treating Parkinson's disease. Brain-targeted liposomes—nanoparticles engineered with transferrin on their surface carry therapeutic antibodies, cross the blood–brain barrier effectively treat brain neurodegeneration. This approach reduces pathological alpha-synuclein aggregation improves motor skills, demonstrating its potential neurodegenerative diseases.
SUMMARY Fibroblasts are the most common cell type found in connective tissues, known to play major roles development, homeostasis, regeneration and disease. Although specific fibroblast subpopulations were associated with different biological processes, mechanisms unique activities underlying their diversity has not been thoroughly examined. Turning skeletal muscle we set dissect variation of muscle-resident fibroblasts (mrFibroblasts). Our results demonstrate mrFibroblasts diversify...
Abstract Crosstalk between multiple components underlies the formation of mature vessels. Although players involved in angiogenesis have been identified, mechanisms underlying crosstalk them are still unclear. Using ex vivo aortic ring assay, we set out to dissect interactions two key angiogenic signaling pathways, vascular endothelial growth factor (VEGF) and transforming β (TGFβ), with members lysyl oxidase (LOX) family matrix modifying enzymes. We find an interplay VEGF, TGFβ, LOXs is...
Abstract Distinct, seemingly independent, cellular pathways affecting intracellular machineries or extracellular matrix (ECM) deposition and organization, have been implicated in aneurysm formation. One of the key genes associated with pathology both humans mice is Lysyl oxidase (LOX), a secreted ECM-modifying enzyme, highly expressed medial vascular smooth muscle cells. To dissect mechanisms leading to development, we conditionally deleted Lox We find that cytoskeletal organization lost...