Tali Ben-Zur, Ph.D.
Calpain KO using the CRISPR- CAS9 as a potential treatment for Alzheimer Disease (AD)
Calpains - calcium-regulated cysteine proteases - are overexpressed in AD. Calpains control the trafficking of the amyloid precursor protein (APP) and regulate the phosphorylation and proteolysis of tau, both of them highly involved in the AD pathology. My objective is to induce knock out of Calpain in-vivo using the CRISPR-CAS9 system, which may constitute a potential treatment for AD.
Caspase-6 knock-out using CRISPR/Cas9 improves cognitive behavior in the 3xTg mouse model of Alzheimer’s disease
My research focuses on Alzheimer’s disease and the mechanisms that lead to its pathologies. I will investigate the role of Caspase 6 and attempt to inhibit its activity in order to suppress β-amyloid depositions and plaque formations. To this end, I will use CRISPR/Cas9 gene editing to knock-out theCaspase 6 gene In-Vivo.
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.
The Big Potential of the Small Nanovesicles
Numerous types of cells can communicate through the secretion of small nano-vesicles containing genetic information. This communication is crucial for the function of the cell and the organism. Mesenchymal stem cells are adult stem cells with unique therapeutic abilities such as tissue regeneration and immunomodulation. In my PhD, I am focusing on exosomes derived from Mesenchymal stem cells as therapeutic candidates to psychiatric, and neurodegenerative disorders.
Feasibility of CRISPR/Cas9 Knockout of PERK for Preventing Pathological Markers of Alzheimer’s Disease
ER stress triggers a protective cellular mechanism in which eukaryotic initiation factor-2α (eIF2α) is phosphorylated. A transient shutdown of general protein synthesis and enhancement of the translation of specific mRNAs associated with Alzheimer’s disease (AD) are the direct outcome of eIF2α phosphorylation. We hope to alleviate AD–related plasticity and memory deficits by the suppression of PERK, an eIF2α-phosphorylating kinase, using the CRISPR/Cas9 technique.
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.
Fragile X is charachterized by expansion of CGG repeats causing DNA hypermethylation and silencing of the FMR1 gene. Despite profound research, there is still no cure for FXS and the treatments are symptomatic. Hence, I plan to study different gene therapy methods, such as CRISPR/Cas9 system for FMR1 gene editing, in knock-out mice and human cells
In-vivo reprogramming towards dopaminergic fate
The regeneration of dopaminergic cells by genetic manipulations in damaged tissue is an innovative approach for a one-time treatment that addresses both the symptoms and the disease source. In my research I use transcription, growth and neurotrophic factors for in-vivo reprogramming towards dopaminergic cells. The aim of this study is to renew the dopamine levels in the dorsal striatum in a one-time treatment.
Alumni Lab Members
Development of nover gene therapy approach for neuroprotection in models of amyotrophic lateral sclerosis.
Mutant Huntingtin proteolysis regulation as a potential treatment for Huntington's disease.
New therapeutic approaches to promote functional outcome and recovery in mouse model of focal ischemic injury
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.