Tali Ben-Zur, Ph.D.
The Role of Exosomes in the Progression and Pathology of Parkinson’s Diseases
Recent in-vitro and in-vivo studies support the idea of transcellular spread of misfolded alpha-synuclein in a prion-like transmission of protein aggregation. It has been established that pathogenic alpha-synuclein can pass from cell to cell via exosome secretion. To better understand the implications of alpha-synuclein propagation via exosomes we would like to inhibit exosome synthesis by chemical and genetic methods such as CRISPR/Cas9 system to reduce alpha-synuclein spread as a therapeutic target and halt the progression of the disease.
Therapeutic effect and mechanism of mesenchymal stem cells-derived exosomes in genetically modified autism model mice Shank3.
Exosomes are small nanovesicles containing molecular information of proteins and RNAs. It has been shown that exosomes derived from mesenchymal stem cells (MSC-Exo) are candidate sources for the therapeutic purposes of various neurological and psychiatric conditions, including autism spectrum disorder (ASD). In my study, I examine the effects of MSC-Exo administration on the behavioral symptoms in the Shank3 mouse model of autism and investigate the molecular mechanism of the MSC-Exo on Shank3 mice.
The role of glutamatergic dysfunction in schizophrenia models
Schizophrenia involves impairments in cognition, perception and motivation.
Recent evidence implicate alterations in glutamatergic neurotransmission in the pathology of schizopgrenia. Our research focuses on this glutamatergic system dysfunction and its role in the pathophysiology of the disease. By utilizing different mouse models for schizophrenia as well as human tissue from individuals with schizophrenia, we aim to offer insight into the pathophysiological processes underlying schizophrenia, and point to future therapeutic targets or biomarkers.
Effects of Modified Mesenchymal Stem Cell-Derived Exosomes in Murine Models of Stroke
Stroke is the second most common cause of death, and the third most common cause of disability worldwide.Research shows MSC-derived exosomes retain some of the characteristics of their parent MSCs, such as immune system modulation, regulation of neurite outgrowth, promotion of angiogenesis, and the ability to repair damaged tissue. In my research a modified MSC-derived exosomes system will be established, in which different molecular agents will be encapsulated into exosomes. Protective effects and therapeutic potential of the modified MSC-derived exosomes will be assessed both in vitro and in various murine models of stroke in vivo
Assessing the role of Neutrophils in Alzheimer's
Recent studies implicate neutrophils in mediating secondary tissue damage in alzheimer's disease. In this work we aim at assesing the role of key neutrophil proteins implicated in the pathologesis of alzheimer's.
Allele-specific correction of disease causing mutations: The CRISPR/Cas system can be employed to specifically target a pathogenic allele and generate an allele-specific double-stranded break. In heterozygous patients such breaks may be corrected by gene conversion as the homologous chromosome serves as the correction template. Otherwise the break will lead to knockout of the pathogenic allele via NHEJ repair pathway. To increase the specificity of the CRISPR system to a single nucleotide we design the gRNAs according to the SNP-derived PAM approach.
Bioinformatic tools for gRNA design: The tools CrisPam and BE-FF were developed from the need of experimentalist researchers to treat specific single-nucleotide variations (SNVs). CrisPam identifies novel PAMs generated by SNVs to design allele-specific alleles. BE-FF (Base editors Functional Finder) identifies base editors that can precisely correct SNVs. Both tools are available as online web tools and were used to generate databases of human pathogenic SNPs that can be edited by SNP-derived PAM or base editing.
The Endocannabinoid (EC) system acts as a neuromodulating network involved in the regulation of emotional responses, behavioral reactivity to context, and social interaction. In addition, medical cannabis was proven as beneficial in several studies for the treatment of chronic pain, emesis and pain in cancer, relieving epilepsy seizures etc. In my research I study the effects of cannbinoid singaling enhancement in mouse models for ASD and pain.
Alumni Lab Members
Caspase-6 knock-out using CRISPR/Cas9 improves cognitive behavior in the 3xTg mouse model of Alzheimer’s disease
The Big Potential of the Small Nanovesicles
Calpain KO using the CRISPR- CAS9 as a potential treatment for Alzheimer Disease (AD)
In-vivo reprogramming towards dopaminergic fate
Development of nover gene therapy approach for neuroprotection in models of amyotrophic lateral sclerosis.
New therapeutic approaches to promote functional outcome and recovery in mouse model of focal ischemic injury
Mutant Huntingtin proteolysis regulation as a potential treatment for Huntington's disease.
Development of genetic and pharmacological approaches for enhancing neuroprotection and nerve regeneration.
Netta Shraga (Blondheim)
Potential Use of Bone Marrow Derived Mesenchymal Stem Cells for Treatment of Multiple Sclerosis
Neurotrophic factors-secreting Mesenchymal stem cells for the therapy of neurodegenerative disease models
Induction of dopaminergic differentiation on human bone marrow stem cells as possible cellular therapy for Parkinson's disease.
Induction of human bone-marrow derived Mesenchymal stem cells differentiation towards dopaminergic fates.