A5062626387- Ion channel regulation and function
- Neurogenetic and Muscular Disorders Research
- Cancer, Hypoxia, and Metabolism
- Amyotrophic Lateral Sclerosis Research
- Mitochondrial Function and Pathology
- Cellular transport and secretion
- Neuroscience and Neural Engineering
- Prenatal Screening and Diagnostics
- Myasthenia Gravis and Thymoma
- Neuroscience and Neuropharmacology Research
- Muscle Physiology and Disorders
- Adipose Tissue and Metabolism
- Neuroinflammation and Neurodegeneration Mechanisms
- Autoimmune Neurological Disorders and Treatments
- Dermatological and COVID-19 studies
- Epigenetics and DNA Methylation
- Cardiac Structural Anomalies and Repair
- bioluminescence and chemiluminescence research
- Parvovirus B19 Infection Studies
- Genetic Syndromes and Imprinting
- biodegradable polymer synthesis and properties
- Cancer, Lipids, and Metabolism
- Mechanical Circulatory Support Devices
- Ubiquitin and proteasome pathways
- Autophagy in Disease and Therapy
University of Pittsburgh
2022-2024
University of Kansas Medical Center
2017-2024
University of Kansas
2012-2021
The Ohio State University Wexner Medical Center
2018
Abstract Presynaptic active zones play a pivotal role as synaptic vesicle release sites for transmission, but the molecular architecture of in mammalian neuromuscular junctions (NMJs) at sub-diffraction limited resolution remains unknown. Bassoon and Piccolo are zone specific cytosolic proteins essential assembly NMJs, ribbon synapses brain synapses. These thought to colocalize share some functions zones. Here, we report an unexpected finding non-overlapping localization these two mouse NMJs...
Motor neurons in amyotrophic lateral sclerosis (ALS) patients and animal models show degeneration from the nerve terminal, known as dying-back neuropathy. To investigate mechanism underlying this neuropathy, we analyzed neuromuscular junctions (NMJs) motor neuron cell bodies SOD1G93A mice using electron microscopy. NMJs of exhibited significantly higher numbers autophagosomes degenerated mitochondria compared to wild-type controls. Mitophagosomes were identified NMJ presynaptic terminals...
Human parvovirus B19 (B19V) infection of human erythroid progenitor cells (EPCs) induces a DNA damage response and cell cycle arrest at late S phase, which facilitates viral replication. However, it is not clear exactly cellular factors are employed by this single-stranded virus. Here, we used microarrays to systematically analyze the dynamic transcriptome EPCs infected with B19V. We found that metabolism, replication, repair, response, cycle, pathways were significantly regulated after B19V...
Stroke is a major neurological disorder characterized by an increase in the Glu (glutamate) concentration resulting excitotoxicity and eventually cellular damage death brain. HIF-1 (hypoxia-inducible factor-1), transcription factor, plays important protective role promoting adaptation to hypoxic conditions. It known that HIF-1α, regulatable subunit of HIF-1, expressed astrocytes under severe ischaemia. However, effect on following toxicity during ischaemia has not been well studied. We...
Hypoxia inducible factor-1 (HIF-1) is a key regulator in hypoxia and can determine the fate of brain cells during ischemia. However, mechanism HIF-1 regulation still not fully understood ischemic brains. We tested hypothesis that both 26S 20S proteasomal pathways were involved HIF-1α degradation under conditions. Using vitro model (oxygen glucose deprivation) mouse middle cerebral artery occlusion, we effects inhibitors proteasomes prolyl hydroxylase (PHD) on stability injury observed 30 60...
Ischemia initiates a complicated biochemical cascade of events that triggers neuronal death. This study focuses on glutamate-mediated tolerance to ischemia–reperfusion. We employed an animal model lifelong excess release glutamate, the glutamate dehydrogenase 1 transgenic (Tg) mouse, as in vivo preconditioning. Nine- and twenty-two-month-old Tg wild-type (wt) mice were subjected 90 min middle cerebral artery occlusion, followed by 24 hr reperfusion. The suffered significantly reduced...
Spinal muscular atrophy (SMA) is a monogenic disease that clinically manifests as severe muscle weakness owing to neurotransmission defects and motoneuron degeneration. Individuals affected by SMA experience neuromuscular impacts functional activities of daily living. We have used mouse model (SMNΔ7) test whether calcium channel gating modifier (GV-58), alone or in combination with potassium antagonist (3,4-diaminopyridine; 3,4-DAP), can improve function this model. Bath application GV-58...
Amyotrophic lateral sclerosis (ALS) remains a devastating motor neuron disease with limited treatment options. Oxaloacetate has neuroprotective effect in rodent models of seizure and neurodegeneration. Therefore, we treated the ALS model superoxide dismutase 1 (SOD1) G93A mice oxaloacetate evaluated their neuromuscular function lifespan. Treatment beginning presymptomatic stage significantly improved strength measured during symptomatic injected compared to non-treated group. starting...
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune-mediated neuromuscular disease thought to be caused by autoantibodies against P/Q-type voltage-gated calcium channels (VGCCs), which attack and reduce the number of VGCCs within transmitter release sites (active zones; AZs) at junction (NMJ), resulting in weakness. However, patients with LEMS also have antibodies other neuronal proteins, about 15% are seronegative for VGCCs. We hypothesized that a reduction alone not sufficient...
Abstract Despite prior efforts to understand and target dynapenia (age‐induced loss of muscle strength), this condition remains a major challenge that reduces the quality life in aged population. We have focused on neuromuscular junction (NMJ) where changes structure function rarely been systematically studied as dynamic progressive process. Our cross‐sectional study found neurotransmission at male mouse NMJ be biphasic, displaying an early increase followed by later decrease, phenotype was...
Amyotrophic lateral sclerosis (ALS) patients lack effective treatments to maintain motor and neuromuscular function. This study aimed evaluate the effect of a home-based exercise program on muscle strength, ALS scores, transcriptome in patients, Clinical Trials.gov #NCT03201991 (28/06/2017). An open-label, non-randomized pilot clinical trial was conducted seven individuals with early-stage ALS. Participants were given 3 months resistance focusing quadriceps muscles. The strength exercised...
SPECC1L cytoskeletal protein is known to associate with microtubules via its second coiled coil domain and actin filaments a C-terminal calponin homology (CHD). Autosomal dominant point mutations in cluster these two domains result range of defects, including craniofacial malformations, omphalocele, as well intellectual disability autism. To study function, we generated many mouse alleles, one truncation the 510 amino acids that also removes CHD (ΔC510). Homozygous ΔC510 mutants are...