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Research Expertise & Professional Interests Dr. Wolozin’s research examines the pathophysiology of neurodegenerative diseases, including Alzheimer’s disease, Amyotrophic Lateral Sclerosis and Parkinson’s disease. His laboratory is currently focused on the role of RNA binding proteins and translational regulation in disease processes. Parkinson’s disease: The research on Parkinson Disease focuses on genetic factors implicated in Parkinson’s disease, including LRRK2, a-synuclein, parkin, PINK1 and DJ-1. Research in our laboratory suggests that genetic mutations linked to Parkinson’s disease act by converging on a biological system that integrates the stress response, regulating autophagy, protein translation and mitochondrial function. Using genetically modified cells (e.g., primary neuronal cultures or cell lines) and genetically modified animals (C. elegans and mice), we have demonstrated that a-synuclein and LRRK2 enhance the sensitivity of dopaminergic neurons to mitochondrial dysfunction. Our work points to particular biochemical pathways mediating the actions of LRRK2. We have recently demonstrated that LRRK2 binds to MKK6, a kinase that lies upstream of p38 and regulates the stress response. LRRK2 regulates membrane localization of its binding proteins, including MKKs, JIPs, rac1 (a small GTPase) and other important proteins mediating the stress response. This work has direct relevance to therapy because it points to chemicals that might protect dopaminergic neurons and modify the course of Parkinson’s disease. For instance, we are investigating the action of SirT1 agonists (such resveratrol, the compound found in red wine or SRT1720, produced by Sirtris Pharmaceuticals), which stimulate synthesis of anti-oxidant enzymes and appear to offer protection in animal models of Parkinson’s disease. We are also investigating the action of brain penetrant analogues of rapamycin, which stimulate the neuron to remove protein aggregates, and offer neuroprotection through mechanisms complementary to SirT1. Amyotrophic Lateral Sclerosis (ALS): Our current work focuses on a protein, TDP-43, that was recently shown to be the predominant protein that accumulates during the course of the disease. We have shown that TDP-43 is a stress granule protein, and that TDP-43 pathology co-localizes with other stress granule markers in spinal cords of subjects with ALS, as well as those with Frontotemporal Dementia. We are currently examining how TDP-43 and disease-linked mutations in TDP-43 modify synaptic function in neuronal arbors. We are using protein binding assays (immunoprecipitation, mass spectrometry) and imaging assay (fixed cells and live cell imaging) to determine the effects of TDP-43 and its mutations. We use cell lines, primary cultures of hippocampal neurons and human brain samples for our studies. We also have an active drug discover program related to TDP-43. This program utilizes cells that inducibly over-express TDP-43, as well as lines of C. elegans expressing TDP-43 and studies in primary cultures of hippocampal neurons. We examine the compounds using imaging (in collaboration with Marcie Glicksman at LDDN) and biochemistry. Alzheimer disease (AD): We have recently extended our work on stress granules to Alzheimer’s disease. As with ALS, we have shown that tau pathology (neurofibrillary tangles) in the AD brain co-localizes with stress granule markers. The amount of stress granule pathology in the AD brain is very striking. Proteins such as TIA-1, G3BP and TTP, strongly accumulate. Interestingly, though, the pattern of accumulation differs based on the stress granule protein. The pathology appears to correlate with binding to tau protein. TIA-1 and TTP both bind to tau, while G3BP does not bind tau. Stress granules might also directly modulate tau pathology, because co-transfecting TIA-1 with tau induces formation of phosphorylated tau inclusions. The work on AD and stress granules uses biochemical/immunochemical studies focusing on proteins implicated in AD (e.g., antibodies to tau) and on stress granule markers. The work also uses extensive imaging assays (fixed cells, live cell imaging, confocal microscopy). We use studies of hippocampal neurons grown culture, transgenic mice expressing P301L tau and human tissues.

One or more keywords matched the following items that are connected to Wolozin, Benjamin

Item TypeName
Concept Protein Kinase C
Concept Protein Kinases
Concept Protein-Tyrosine Kinases
Concept Protein-Serine-Threonine Kinases
Concept Phosphotransferases (Alcohol Group Acceptor)
Concept Calcium-Calmodulin-Dependent Protein Kinases
Concept Phosphatidylinositol 3-Kinases
Concept Mitogen-Activated Protein Kinase 1
Concept Mitogen-Activated Protein Kinases
Concept Mitogen-Activated Protein Kinase Kinases
Concept MAP Kinase Signaling System
Concept Glycogen Synthase Kinases
Concept Glycogen Synthase Kinase 3
Concept Protein Kinase Inhibitors
Concept JNK Mitogen-Activated Protein Kinases
Concept Extracellular Signal-Regulated MAP Kinases
Concept p38 Mitogen-Activated Protein Kinases
Concept Mitogen-Activated Protein Kinase 3
Concept MAP Kinase Kinase 2
Concept MAP Kinase Kinase 6
Concept MAP Kinase Kinase 4
Concept Focal Adhesion Protein-Tyrosine Kinases
Concept Focal Adhesion Kinase 1
Concept Protein Kinase C-alpha
Academic Article Isolation of a cDNA encoding the human brain serotonin transporter.
Academic Article Human olfactory neuroepithelial cells: tyrosine phosphorylation and process extension are increased by the combination of IL-1beta, IL-6, NGF, and bFGF.
Academic Article Physiologic levels of beta-amyloid activate phosphatidylinositol 3-kinase with the involvement of tyrosine phosphorylation.
Academic Article Physiological levels of beta-amyloid peptide stimulate protein kinase C in PC12 cells.
Academic Article Amyloid precursor protein requires the insulin signaling pathway for neurotrophic activity.
Academic Article Beta-amyloid augments platelet aggregation: reduced activity of familial angiopathy-associated mutants.
Academic Article Regulation of apoptosis by presenilin 1.
Academic Article Presenilin 1 associates with glycogen synthase kinase-3beta and its substrate tau.
Academic Article alpha-Synuclein shares physical and functional homology with 14-3-3 proteins.
Academic Article Regulation of amyloid precursor protein processing by presenilin 1 (PS1) and PS2 in PS1 knockout cells.
Academic Article Presenilin 1 regulates beta-catenin-mediated transcription in a glycogen synthase kinase-3-independent fashion.
Academic Article Differential expression of cholesterol hydroxylases in Alzheimer's disease.
Academic Article Tau phosphorylation increases in symptomatic mice overexpressing A30P alpha-synuclein.
Academic Article Investigating convergent actions of genes linked to familial Parkinson's disease.
Academic Article Leucine-rich repeat kinase 2 induces alpha-synuclein expression via the extracellular signal-regulated kinase pathway.
Academic Article The Parkinson's disease associated LRRK2 exhibits weaker in vitro phosphorylation of 4E-BP compared to autophosphorylation.
Academic Article LRRK2 modulates vulnerability to mitochondrial dysfunction in Caenorhabditis elegans.
Academic Article MKK6 binds and regulates expression of Parkinson's disease-related protein LRRK2.
Academic Article LRRK2 and the stress response: interaction with MKKs and JNK-interacting proteins.
Academic Article Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue.
Academic Article Rac1 protein rescues neurite retraction caused by G2019S leucine-rich repeat kinase 2 (LRRK2).
Academic Article Regulation of physiologic actions of LRRK2: focus on autophagy.
Academic Article Redox proteomics analyses of the influence of co-expression of wild-type or mutated LRRK2 and Tau on C. elegans protein expression and oxidative modification: relevance to Parkinson disease.
Academic Article The heat shock transcription factor Hsf1 is downregulated in DNA damage-associated senescence, contributing to the maintenance of senescence phenotype.
Academic Article Physiological levels of beta-amyloid increase tyrosine phosphorylation and cytosolic calcium.
Academic Article Mutations in LRRK2 potentiate age-related impairment of autophagic flux.
Academic Article A Parkinson''s disease gene regulatory network identifies the signaling protein RGS2 as a modulator of LRRK2 activity and neuronal toxicity.
Academic Article Interaction of LRRK2 with kinase and GTPase signaling cascades.
Academic Article LRRK2 and RAB7L1 coordinately regulate axonal morphology and lysosome integrity in diverse cellular contexts.
Academic Article Syk and Yea Shall Find.
Academic Article Interaction of tau with the RNA-Binding Protein TIA1 Regulates tau Pathophysiology and Toxicity.

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