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Search Results to Benjamin Wolozin, MD, PhD

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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.
Self-Described Keywords gene over-expression
Self-Described Keywords gene knockdown

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

Item TypeName
Concept Alleles
Concept Amino Acid Sequence
Concept Base Sequence
Concept Gene Expression Regulation
Concept Genes
Concept Lac Operon
Concept Molecular Sequence Data
Concept Sequence Homology, Nucleic Acid
Concept Gene Library
Concept Calcitonin Gene-Related Peptide
Concept Gene Expression
Concept Gene Expression Regulation, Enzymologic
Concept Open Reading Frames
Concept Consensus Sequence
Concept Gene Deletion
Concept Sequence Homology
Concept Sequence Homology, Amino Acid
Concept Genes, Reporter
Concept Transgenes
Concept Gene Regulatory Networks
Concept Gene Knockdown Techniques
Concept Transcriptome
Academic Article Requirement of the familial Alzheimer's disease gene PS2 for apoptosis. Opposing effect of ALG-3.
Academic Article Changes in gene transcription during a beta-mediated cell death.
Academic Article Regional brain expression of serotonin transporter mRNA and its regulation by reuptake inhibiting antidepressants.
Academic Article Direct association of presenilin-1 with beta-catenin.
Academic Article FMR1 gene expression in olfactory neuroblasts from two males with fragile X syndrome.
Academic Article alpha-Synuclein shares physical and functional homology with 14-3-3 proteins.
Academic Article A fluid connection: cholesterol and Abeta.
Academic Article Continuous culture of neuronal cells from adult human olfactory epithelium.
Academic Article Parkin protects against the toxicity associated with mutant alpha-synuclein: proteasome dysfunction selectively affects catecholaminergic neurons.
Academic Article Differential expression of carboxyl terminal derivatives of amyloid precursor protein among cell lines.
Academic Article Serotonin (5-HT) receptor, 5-HT transporter and G protein-effector expression: implications for depression.
Academic Article Aggregated and monomeric alpha-synuclein bind to the S6' proteasomal protein and inhibit proteasomal function.
Academic Article Differential expression of cholesterol hydroxylases in Alzheimer's disease.
Academic Article Similar patterns of mitochondrial vulnerability and rescue induced by genetic modification of alpha-synuclein, parkin, and DJ-1 in Caenorhabditis elegans.
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 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 Tar DNA binding protein-43 (TDP-43) associates with stress granules: analysis of cultured cells and pathological brain tissue.
Academic Article Pathogenic LRRK2 mutations do not alter gene expression in cell model systems or human brain tissue.
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 Correction: Pathogenic LRRK2 Mutations Do Not Alter Gene Expression in Cell Model Systems or Human Brain Tissue.
Academic Article Neuronal-specific overexpression of a mutant valosin-containing protein associated with IBMPFD promotes aberrant ubiquitin and TDP-43 accumulation and cognitive dysfunction in transgenic mice.
Academic Article Norepinephrine, serotonin and vesicular monoamine transporter in depression and bipolar disorder
Academic Article Genes, Behaviour and Health
Academic Article DJ-1 Expression Increases in Mice Over-Expressing A30P a-Synuclein
Academic Article Development of neuropathology similar to Alzheimer's Disease in transgenic mice overexpressing the 717V-F b-amyloid precursor protein
Academic Article Fluoxetine modulates G protein alpha s, alpha q, and alpha 12 subunit mRNA expression in rat brain.
Academic Article Organization of the human serotonin transporter gene.
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 A high-content screen identifies novel compounds that inhibit stress-induced TDP-43 cellular aggregation and associated cytotoxicity.
Academic Article Increased cytoplasmic TDP-43 reduces global protein synthesis by interacting with RACK1 on polyribosomes.
Academic Article Amylin receptor ligands reduce the pathological cascade of Alzheimer''s disease.
Academic Article Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo.
Academic Article Directed evolution of a picomolar-affinity, high-specificity antibody targeting phosphorylated tau.

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