A5085653330- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Neurobiology and Insect Physiology Research
- Lipid Membrane Structure and Behavior
- Genetic Neurodegenerative Diseases
- Developmental Biology and Gene Regulation
- Cellular Mechanics and Interactions
- Extracellular vesicles in disease
- Cardiomyopathy and Myosin Studies
- RNA Interference and Gene Delivery
- Coenzyme Q10 studies and effects
- Mosquito-borne diseases and control
- Neuroscience and Neuropharmacology Research
- Insect symbiosis and bacterial influences
- Luminescence and Fluorescent Materials
- Amyotrophic Lateral Sclerosis Research
- Muscle Physiology and Disorders
- Advanced biosensing and bioanalysis techniques
- Neurological disorders and treatments
- Skin and Cellular Biology Research
- Supramolecular Self-Assembly in Materials
- Photoreceptor and optogenetics research
- RNA regulation and disease
- Autophagy in Disease and Therapy
- Hippo pathway signaling and YAP/TAZ
Brandeis University
2015-2024
Tufts University
2012-2018
Concord Consortium
2008
Boston University
2005-2006
Geriatric Research Education and Clinical Center
2005
Bedford VA Research Corporation
2005
Abstract Genetic murine models play an important role in the study of human neurological disorders by providing accurate and experimentally accessible systems to pathogenesis test potential therapeutic treatments. One most widely employed Huntington's disease (HD) is R6/2 transgenic mouse. To characterize this model further, we have performed behavioral neuropathological analyses that provide a foundation for use mice preclinical trials. Behavioral mouse reveal age‐related impairments...
Despite the advancement of molecular imaging techniques, there is an unmet need for probes direct membrane dynamics live cells. Here we report a novel type active (or enzyme responsive) to directly image cells with high spatial and temporal resolution over extended time scales areas. Because lipid rafts enrich cholesterols GPI-anchored enzymes (e.g., ectophosphatases), design that consist enzymatic trigger, fluorophore, cholesterol are affinitive cell membrane. Being water-soluble as...
Release of mitochondrial cytochrome c resulting in downstream activation cell death pathways has been suggested to play a role neurologic diseases featuring death. However, the specific biologic importance release not demonstrated Huntington's disease (HD). To evaluate release, we screened drug library identify new inhibitors from mitochondria. Drugs effective at level purified mitochondria were evaluated cellular model HD. As proof principle, one was chosen for depth evaluation vitro and...
Recent evidence suggests that transcriptional dysregulation may play a role in the pathogenesis of amyotrophic lateral sclerosis (ALS). The histone deacetylase inhibitor, sodium phenylbutyrate (NaPB), is neuroprotective and corrects aberrant gene transcription ALS mice has recently been shown to be safe tolerable patients while improving hypoacetylation. Since many are already on riluzole, it important ensure any proposed therapy does not result negative synergy with riluzole. combined...
Synaptic membrane-remodeling events such as endocytosis require force-generating actin assembly. The endocytic machinery that regulates these and membrane dynamics localizes at high concentrations to large areas of the presynaptic membrane, but assembly productive are far more restricted in space time. Here we describe a mechanism whereby autoinhibition clamps limit discrete functional events. We found collective interactions between Drosophila proteins Nwk/FCHSD2, Dap160/intersectin, WASp...
Extracellular vesicles (EVs) are released by many cell types, including neurons, carrying cargoes involved in signaling and disease. It is unclear whether EVs promote intercellular or serve primarily to dispose of unwanted materials. We show that loss multivesicular endosome-generating endosomal sorting complex required for transport (ESCRT) machinery disrupts release EV from Drosophila motor neurons. Surprisingly, ESCRT depletion does not affect the activities cargo Synaptotagmin-4 (Syt4)...
Most of the peptides used for promoting cellular uptake bear positive charges. In our previous study, we reported an example taurine (bearing negative charges in physiological conditions) D-peptides. Taurine, conjugated to a small D-peptide via ester bond, promotes this D-peptide. Particularly, intracellular carboxylesterase (CES) instructs self-assemble and form nanofibers, which largely disfavors efflux further enhances accumulation D-peptide, as supported by that addition CES inhibitors...
Lowe Syndrome is a developmental disorder characterized by eye, kidney, and neurological pathologies, caused mutations in the phosphatidylinositol-5-phosphatase OCRL. OCRL plays diverse roles endocytic endolysosomal trafficking, cytokinesis, ciliogenesis, but it unclear which of these cellular functions underlie specific patient symptoms. Here, we show that mutation Drosophila causes cell-autonomous activation hemocytes, are macrophage-like cells innate immune system. Among many cell...
Following exocytosis at active zones, synaptic vesicle membranes and membrane-bound proteins must be recycled. The endocytic machinery that drives this recycling accumulates in the periactive zone (PAZ), a region of synapse adjacent to but organization within PAZ, how PAZ composition relates release properties, remains unknown. is also enriched for cell adhesion proteins, their function these sites poorly understood. Here, using Airyscan stimulated emission depletion imaging Drosophila...
Abstract Synaptic membrane-remodeling events such as endocytosis require force-generating actin assembly. The endocytic machinery that regulates these and membrane dynamics localizes at high concentrations to large areas of the presynaptic membrane, but assembly productive are far more restricted in space time. Here we describe a mechanism whereby autoinhibition clamps limit discrete functional events. We found collective interactions between Drosophila proteins Nwk/FCHSD2,...
Extracellular vesicles (EVs) are released by many cell types including neurons, carrying cargoes involved in signaling and disease. It is unclear whether EVs promote intercellular or serve primarily to dispose of unwanted materials. We show that loss multivesicular endosome-generating ESCRT (endosomal sorting complex required for transport) machinery disrupts release EV from Drosophila motor neurons. Surprisingly, depletion does not affect the activities cargo Synaptotagmin-4 (Syt4) only...
1. Abstract Following exocytosis at active zones, synaptic vesicle membranes and membrane-bound proteins must be recycled. The endocytic machinery that drives this recycling accumulates in the periactive zone (PAZ), a region of synapse adjacent to but organization within PAZ, how PAZ composition relates release properties remains unknown. is also enriched for cell adhesion proteins, their function these sites poorly understood. Here, using Airyscan STED imaging Drosophila synapses, we...