A5033396587- Neurogenetic and Muscular Disorders Research
- RNA modifications and cancer
- Muscle Physiology and Disorders
- RNA Research and Splicing
- Congenital Anomalies and Fetal Surgery
- Virus-based gene therapy research
- CRISPR and Genetic Engineering
- Genetic Neurodegenerative Diseases
- Cardiomyopathy and Myosin Studies
- RNA and protein synthesis mechanisms
- Cancer-related gene regulation
- Cardiac Structural Anomalies and Repair
- Muscle metabolism and nutrition
- Genetics and Neurodevelopmental Disorders
- Microfluidic and Capillary Electrophoresis Applications
- Ion channel regulation and function
- RNA Interference and Gene Delivery
- Muscle activation and electromyography studies
- Nuclear Structure and Function
- Silk-based biomaterials and applications
- Viral Infections and Immunology Research
- Amyotrophic Lateral Sclerosis Research
- Advanced Proteomics Techniques and Applications
- Exercise and Physiological Responses
- Protein Tyrosine Phosphatases
The Ohio State University
2015-2024
The Ohio State University Wexner Medical Center
2013-2024
Bexley Hall
2023
State Library of Ohio
2020
Columbus Oncology and Hematology Associates
2013-2017
Nationwide Children's Hospital
2016-2017
Ohio University
2015
Neurological Surgery
2013
deCODE Genetics (Iceland)
2008
Faculty of Public Health
2005
Spinal muscular atrophy type 1 (SMA1) is a progressive, monogenic motor neuron disease with an onset during infancy that results in failure to achieve milestones and death or the need for mechanical ventilation by 2 years of age. We studied functional replacement mutated gene encoding survival (SMN1) this disease.Fifteen patients SMA1 received single dose intravenous adeno-associated virus serotype 9 carrying SMN complementary DNA missing protein. Three low (6.7×1013 vg per kilogram body...
Spinal muscular atrophy (SMA) is an autosomal recessive disorder in humans which results the loss of motor neurons. It caused by reduced levels survival neuron (SMN) protein as a result or mutation SMN1 gene. SMN encoded two genes, and SMN2, essentially differ single nucleotide exon 7. As result, majority transcript from SMN2 lacks 7 (SMNΔ7). SMNΔ7 may be toxic detrimental SMA, which, if true, could lead to adverse effects with drugs that stimulate expression SMN2. To determine role we...
Myoblast transfer has been proposed as a technique to replace dystrophin, the skeletal-muscle protein that is deficient in Duchenne's muscular dystrophy. Donor myoblasts injected into muscles of affected patients can fuse with host muscle fibers, thus contributing their nuclei, which are potentially capable replacing gene products. Previous controlled trials involving single have unsuccessful.
Spinal muscular atrophy (SMA) is an autosomal recessive disorder characterized by a loss of α motoneurons in the spinal cord. SMA caused low levels ubiquitously expressed survival motor neuron (Smn) protein. As it unclear how Smn specifically affect motoneurons, we have modeled zebrafish, vertebrate model organism with well-characterized motoneuron development. Using antisense morpholinos to reduce throughout entire embryo, found axon–specific pathfinding defects. Reduction individual...
Objective Infantile‐onset spinal muscular atrophy (SMA) is the most common genetic cause of infant mortality, typically resulting in death preceding age 2. Clinical trials this population require an understanding disease progression and identification meaningful biomarkers to hasten therapeutic development predict outcomes. Methods A longitudinal, multicenter, prospective natural history study enrolled 26 SMA infants 27 control aged <6 months. Recruitment occurred at 14 centers over 21...
Significance Direct conversion is a recently established method to generate neuronal progenitor cells (NPCs) from skin fibroblasts in fast and efficient manner. In this study, we show that can be used model neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). Because the origin of ALS mainly sporadic with unknown cause, methods disease are urgently needed. The produced NPCs differentiated into astrocytes, which involved motor neuron death ALS. Strikingly, skin-derived...
Adeno-associated virus type 9 (AAV9) is a powerful tool for delivering genes throughout the central nervous system (CNS) following intravenous injection. Preclinical results in pediatric models of spinal muscular atrophy (SMA) and lysosomal storage disorders provide compelling case advancing AAV9 to clinic. An important translational step demonstrate efficient CNS targeting large animals at various ages. In present study, we tested systemically injected cynomolgus macaques, administered...
Spinal muscular atrophy (SMA) is a motor neuron disease caused by reduced levels of the survival (SMN) protein. SMN together with Gemins2-8 and unrip proteins form macromolecular complex that functions in assembly small nuclear ribonucleoproteins (snRNPs) both major minor splicing pathways. It not known whether spliceosomal snRNPs are decreased SMA. Here we analyzed consequence deficiency on snRNP metabolism spinal cord mouse models SMA differing phenotypic severities. We demonstrate...
Spinal muscular atrophy (SMA) is the most frequent lethal genetic neurodegenerative disorder in infants. The disease caused by low abundance of survival motor neuron (SMN) protein leading to degeneration and progressive paralysis. We previously demonstrated that a single intravenous injection (IV) self-complementary adeno-associated virus-9 carrying human SMN cDNA (scAAV9-SMN) resulted widespread transgene expression spinal cord neurons SMA mice as well nonhuman primates complete rescue...
Spinal muscular atrophy (SMA) is an autosomal-recessive disorder characterized by α-motor neuron loss in the spinal cord anterior horn. SMA results from deletion or mutation of Survival Motor Neuron 1 gene (SMN1) and retention SMN2. A single nucleotide difference between SMN1 SMN2 exclusion exon 7 majority transcripts, leading to decreased SMN protein levels development SMA. series splice enhancers silencers regulate incorporation 7; these motifs can be blocked with antisense oligomers...
Spinal muscular atrophy (SMA), the leading genetic cause of infant mortality, arises from survival motor neuron (SMN) protein insufficiency resulting
Spinal muscular atrophy (SMA) is an inherited motor neuron disease caused by mutation of the telomeric copy survival gene (SMN1). Although a centromeric (SMN2) retained in all patients with SMA, it differs from SMN1 at critical nucleotide such that majority SMN2 transcripts lack exon 7 and encode unstable, truncated protein. Here, we show valproic acid increases levels 7-containing SMN transcript protein type I SMA patient-derived fibroblast cell lines. Valproic may increase both activating...
Duchenne muscular dystrophy (DMD) and its less severe form Becker (BMD) are allelic disorders. It has been suggested that in the mutations involving BMD, translational reading frame of messenger RNA is maintained a smaller, though partially functional, protein produced. In order to test this, exon-intron boundaries first ten exons DMD gene were determined, 29 patients analyzed. number BMD (mild BMD), was not maintained. On basis these findings, model for reinitiation from an internal start...
Spinal muscular atrophy (SMA) is caused by loss of the survival motor neuron gene (SMN1) and retention SMN2 gene. The copy number affects amount SMN protein produced severity SMA phenotype. While mouse Smn embryonic lethal, two copies prevents this lethality resulting in a with severe that dies 5 days after birth. Here we show expression full-length under prion promoter (PrP) rescues mice. PrP results high levels neurons at day 15. Mice homozygous for PrP-SMN lacking survive an average 210...