A5066065134- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Histone Deacetylase Inhibitors Research
- Neurobiology and Insect Physiology Research
- Nerve injury and regeneration
- Neurological disorders and treatments
- Cholinesterase and Neurodegenerative Diseases
- CRISPR and Genetic Engineering
- Neuropeptides and Animal Physiology
- Genetics and Neurodevelopmental Disorders
- Signaling Pathways in Disease
- Vascular Malformations and Hemangiomas
- Genetic Neurodegenerative Diseases
- Plant and fungal interactions
- Fungal Biology and Applications
- Mycorrhizal Fungi and Plant Interactions
- Ubiquitin and proteasome pathways
- Viral Infections and Immunology Research
- Invertebrate Immune Response Mechanisms
- Plant Molecular Biology Research
- Insect Utilization and Effects
- Cytomegalovirus and herpesvirus research
- Retinal Development and Disorders
- Forensic Entomology and Diptera Studies
- Heat shock proteins research
Massey University
1999-2024
Neurology, Inc
2007-2010
University of Auckland
2001-2006
Jefferson College
2003
Thomas Jefferson University
2002
The motor abnormalities of Parkinson's disease (PD) are caused by alterations in basal ganglia network activity, including disinhibition the subthalamic nucleus (STN), and excessive activity major output nuclei. Using adeno-associated viral vector–mediated somatic cell gene transfer, we expressed glutamic acid decarboxylase (GAD), enzyme that catalyzes synthesis neurotransmitter GABA, excitatory glutamatergic neurons STN rats. transduced neurons, when driven electrical stimulation, produced...
The brain is generally considered immunoprivileged, although increasing examples of immunological responses to antigens, neuronal expression major histocompatibility class I genes, and neurological autoimmunity have been recognized. An adeno-associated virus (AAV) vaccine generated autoantibodies that targeted a specific protein, the NR1 subunit N -methyl- d -aspartate (NMDA) receptor. After peroral administration AAV vaccine, transgene persisted for at least 5 months was associated with...
We report the characterization of a new rapid-onset model Huntington's disease (HD) generated by adeno-associated virus (AAV) vector–mediated gene transfer N-terminal huntingtin (htt) constructs into rat striatum. Expression exon 1 mutant htt containing 70 CAG repeats rapidly led to neuropathological features associated with HD. In addition, we novel data relating neuronal transduction AAV vectors that modulated phenotype observed in this model. Quantitative reverse transcriptase–polymerase...
Parkinson's disease (PD) is associated with increased excitatory activity within the subthalamic nucleus (STN). We sought to inhibit STN output in hemiparkinsonian macaques by transfection adeno-associated virus (AAV) containing gene for glutamic acid decarboxylase (GAD). In total, 13 were rendered right intracarotid 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine injection. Seven animals injected AAV-GAD into STN, and six received an AAV green fluorescent protein (GFP). Videotaped motor...
A growing body of research indicates that pharmacological inhibition histone deacetylases (HDACs) correlates with enhancement long-term memory and current is concentrated on determining the roles individual HDACs play in cognitive function. Here, we investigate role HDAC4 formation Drosophila. We show overexpression adult mushroom body, an important structure for formation, resulted a specific impairment courtship memory, but had no affect short-term memory. Overexpression catalytic mutant...
Diabetes and its concurrent complications impact a significant proportion of the population US create large financial burden on American health care system. FDA-approved maggot debridement therapy (MDT), application sterile laboratory-reared Lucilia sericata (green bottle fly) larvae to wounds, is cost-effective successful treatment for diabetic foot ulcers other medical conditions. Human platelet derived growth factor-BB (PDGF-BB) secreted dimeric peptide factor that binds PDGF receptor....
Recombinant adeno-associated viruses (rAAV) are highly efficient vectors for gene transfer into the central nervous system (CNS). However, a major hurdle delivery to mammalian brain is achieve high-level transduction in target cells beyond immediate injection site. Therefore, addition improvements expression cassettes and viral titers, optimal parameters need be defined. Here, we show that previous studies of somatic cell have used suboptimal parameters, with even lowest reported perfusion...
Histone deacetylase four (HDAC4) undergoes dynamic nucleocytoplasmic shuttling, which is important in the regulation of its activity. However, aberrant nuclear accumulation HDAC4 associated with both neurodevelopmental and neurodegenerative disease, our Drosophila model, impairs normal neuronal development. Upon accumulation, forms biomolecular condensates, previously termed aggregates, that correlate severity defects development mushroom body adult eye. Here we determined condensation...
There is increasing evidence that regulation of local chromatin structure a critical mechanism underlying the consolidation long-term memory (LTM), however considerably less understood about specific mechanisms by which these epigenetic effects are mediated. Furthermore, importance histone acetylation in Drosophila has not been reported. The deacetylase (HDAC) Rpd3 abundant adult fly brain, suggesting post-mitotic function. Here, we investigated role courtship Drosophila. We found while...
HDAC4 is a potent memory repressor with overexpression of wild type or nuclear-restricted mutant resulting in deficits. Interestingly, reduction also impairs via an as yet unknown mechanism. Although histone deacetylase family members are important mediators epigenetic mechanisms neurons, predominantly cytoplasmic the brain and there increasing evidence for interactions nonhistone proteins, suggesting has roles beyond transcriptional regulation. To that end, we performed genetic interaction...
Moesin is a cytoskeletal adaptor protein that plays an important role in modification of the actin cytoskeleton. Rearrangement cytoskeleton drives both neuronal morphogenesis and structural changes neurons are required for long-term memory formation. has been identified as candidate gene Drosophila, however, whether it formation not evaluated. Here, we investigate short- courtship suppression assay, model associative memory. We found knockdown overexpression led to defects axon growth...
Summary Cell–cell fusion in fungi is required for colony formation, nutrient transfer and signal transduction. Disruption of genes hyphal Epichloë festucae , a mutualistic symbiont Lolium grasses, severely disrupts the host interaction phenotype. They examined whether symB symC E. homologs Podospora anserina self‐signaling IDC2 IDC3 are symbiosis. Deletion mutants these were defective cell fusion, formed intra‐hyphal hyphae, had enhanced conidiation. SymB‐GFP SymC‐mRFP1 localize to plasma...
Summary In both Sordaria macrospora and Neurospora crassa , components of the conserved STRIPAK (striatin‐interacting phosphatase kinase) complex regulate cell–cell fusion, hyphal network development fruiting body formation. Interestingly, a number Epichloë festucae genes that are required for such as noxA noxR proA mpkA mkkA also establishment mutualistic symbiotic interaction with Lolium perenne . To determine whether MobC, homologue component MOB3 in S. N. is E. fusion symbiosis, mobC...
Spatial and temporal control of gene expression in Drosophila is essential elucidating function. facilitated by the UAS/GAL4 system, this can be coupled with additional adaptations for precise fine tuning levels. Here we directly compare level pan-neuronal transgene governed nSyb-GAL4 elav-GAL4, as well mushroom body-specific alongside OK107-GAL4. We also modulation neurons auxin-inducible system (AGES) regional targeting (TARGET) systems.
Dysregulation of the histone deacetylase HDAC4 is associated with both neurodevelopmental and neurodegenerative disorders, a feature common to many these disorders impaired cognitive function. shuttles between nucleus cytoplasm in vertebrates invertebrates alterations amounts nuclear and/or cytoplasmic have been implicated diseases. In Drosophila, also plays critical role regulation memory, however, mechanisms through which it acts are unknown. Nuclear cytoplasmically-restricted mutants were...
Dysregulation of HDAC4 expression and/or nucleocytoplasmic shuttling results in impaired neuronal morphogenesis and long-term memory Drosophila melanogaster. A recent genetic screen for genes that interact the same molecular pathway as identified cytoskeletal adapter Ankyrin2 (Ank2). Here we sought to investigate role Ank2 morphogenesis, learning memory. We found is expressed widely throughout brain where it localizes predominantly axon tracts. Pan-neuronal knockdown mushroom body, a region...