A5005737782- Adipose Tissue and Metabolism
- Virus-based gene therapy research
- Pancreatic function and diabetes
- Lysosomal Storage Disorders Research
- Neurotransmitter Receptor Influence on Behavior
- Sirtuins and Resveratrol in Medicine
- Regulation of Appetite and Obesity
- Viral Infectious Diseases and Gene Expression in Insects
- Nerve injury and regeneration
- Neuroscience and Neuropharmacology Research
- Nuclear Receptors and Signaling
- Adipokines, Inflammation, and Metabolic Diseases
- Memory and Neural Mechanisms
- Neuroinflammation and Neurodegeneration Mechanisms
- Hearing, Cochlea, Tinnitus, Genetics
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Zebrafish Biomedical Research Applications
- Retinal Development and Disorders
- bioluminescence and chemiluminescence research
- GDF15 and Related Biomarkers
- Hemophilia Treatment and Research
- Endoplasmic Reticulum Stress and Disease
- Aerosol Filtration and Electrostatic Precipitation
- Calpain Protease Function and Regulation
Spark Therapeutics (United States)
2021
The Ohio State University
2007-2017
Neurological Surgery
2010-2015
Cancer Genetics (United States)
2007-2011
Axon degeneration is a hallmark of neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Such not passive event but rather an active process mediated by mechanisms that are distinct from the canonical pathways programmed cell death mediate destruction soma. Little known diverse involved, particularly those retrograde axon degeneration. We have previously observed in living animal models nigrostriatal projection constitutively form kinase, myristoylated Akt...
Abstract Objective: A prevailing concept in neuroscience has been that the adult mammalian central nervous system is incapable of restorative axon regeneration. Recent evidence, however, suggested reactivation intrinsic cellular programs regulated by protein kinase B (Akt)/mammalian target rapamycin (mTor) signaling may restore this ability. Methods: To assess possibility brain, we have examined ability adenoassociated virus (AAV)‐mediated transduction dopaminergic neurons substantia nigra...
Abstract Mucopolysaccharidosis (MPS) IIIB is a lysosomal storage disease with severe neurological manifestations due to α‐ N ‐acetylglucosaminidase (NaGlu) deficiency. The mechanism of neuropathology in MPS unclear. This study investigates the role immune responses mice. By means gene expression microarrays and real‐time quantitative reverse transcriptase–polymerase chain reaction, we demonstrated significant up‐regulation numerous immune‐related genes mouse brain involving broad range cells...
Abstract Living in an enriched environment (EE) decreases adiposity, increases energy expenditure, causes resistance to diet induced obesity, and induces brown-like (beige) cells white fat via activating a hypothalamic-adipocyte axis. Here we report that EE stimulated vascular endothelial growth factor (VEGF) expression depot-specific manner prior the emergence of beige cells. The VEGF up-regulation was independent hypoxia but required intact sympathetic tone adipose tissue. Targeted...
In Parkinson's disease, long-term dopamine replacement therapy is complicated by the appearance of l -DOPA-induced dyskinesia (LID). One major hypothesis that LID results from an aberrant transcriptional program in striatal neurons induced -DOPA and triggered activation ERK. To identify these genes, we performed transcriptome analyses striatum 6-hydroxydopamine-lesioned mice. A time course analysis (0–6 h after treatment with -DOPA) identified acute signature 709 among which genes involved...
Adipose tissue plays an essential role in metabolic homeostasis and holds promise as alternative depot organ gene therapy. However, efficient methods of transfer into adipose vivo have yet to be established. Here, we assessed the transduction efficiency fat depots by a family novel engineered hybrid capsid serotypes (Rec1∼4) recombinant adeno-associated viral (AAV) vectors comparison with natural AAV1, AAV8, AAV9. Rec2 serotype led widespread both brown white highest among seven tested. As...
Mucopolysaccharidosis type VII is a lysosomal storage disease caused by deficiency of the acid hydrolase beta-glucuronidase. MPS mice develop progressive accumulation glycosaminoglycans within multiple organs, including brain. Using this animal model, we investigated whether gene transfer mediated recombinant adeno-associated virus (rAAV) 2 vector capable reversing progression in adult mice. We engineered an rAAV2 to carry murine beta-glucuronidase cDNA under transcriptional direction human...
Recombinant adeno-associated virus (rAAV) vectors are attractive vehicles for gene therapy. Gene delivery to the adipose tissue using naturally occurring AAV serotypes is less successful compared liver and muscle. Here, we demonstrate that oral administration of an engineered serotype Rec2 led preferential transduction brown fat with absence in gastrointestinal track. Among six natural being compared, was most efficient achieving high level at a dose 1~2 orders lower than reported doses...
Activation-induced cytidine deaminase (AID) is an enzyme essential for the generation of Ab diversity in B cells and considered to be a general gene mutator. In addition, AID expression was also implicated pathogenesis human cell malignancies associated with poor prognosis. this study, we report that small interfering RNA silencing plasmacytoma dramatically increased its susceptibility immunotherapy by CTLs. did not decrease mutation frequencies tumor Ag P1A. Gene-array analysis showed...
Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in learning, we tested whether cells this region play a role CPP. We found that intracranial injections adenoassociated virus (AAV) expressing wild-type (WT) into mPFC KO rescued and injection AAV dominant negative form (NarpN) WT These findings suggest mediates
Extensive clinical data from liver-mediated gene therapy trials have shown that dose-dependent immune responses against the vector capsid may impair or even preclude transgene expression if not managed successfully with prompt suppression. The goal of this preclinical study was to generate an adeno-associated viral (AAV) capable expressing therapeutic levels B-domain deleted factor VIII (FVIII) at lowest possible dose minimize potential Risk a capsid-mediated response in setting. Here, we...
Dopamine signaling in the nucleus accumbens is critical mediating effects of cocaine. There are two splice variants dopamine D2 receptors, D2L and D2S, which believed to have different functional roles. Here, we show, that knocking down selectively using viral-mediated short-hairpin RNA led a slight but significant decrease basal locomotor activity with no change cocaine-induced stimulation locomotion. The knockdown appears produce trend reduced conditioned place preference cocaine...
The medial prefrontal cortex (mPFC) plays a key role in extinction learning. Previously, we found that expression of neuronal activity-regulated pentraxin (Narp) dominant-negative construct the mPFC mice blocked morphine-conditioned place preference. To further investigate Narp drug seeking, tested whether is necessary for heroin self-administration rats. Specifically, injected an adeno-associated viral vector expressing form (NarpN) into infralimbic region rats and compared lever presses...
Background The combination of gene therapy and plastic surgery may have the potential to improve specificity that is needed achieve clinically applicable treatment regimens. Our goal was develop a method for modification would yield sustainable production products but be less time consuming than existing protocols. Methods An adenoassociated virus used deliver pectoralis muscle flaps. Gene accomplished via either direct injection or novel fat grafting techniques. Results product observable...
Mucopolysaccharidosis type VII (MPS VII; Sly disease) is a lysosomal storage disease (LSD) caused by deficiency of the acid hydrolase β-glucuronidase. Deficiency this enzyme results in accumulation glycosaminoglycans most organs, including brain. In mouse model disorder, widespread correction central nervous system manifestations has not been observed with peripherally administered therapies adult animals. The objective study was to evaluate effect peripheral administration an rAAV vector on...