A5057854320- Neuroscience and Neuropharmacology Research
- Ion channel regulation and function
- Mesenchymal stem cell research
- Genetics and Neurodevelopmental Disorders
- Receptor Mechanisms and Signaling
- RNA Research and Splicing
- Neuroinflammation and Neurodegeneration Mechanisms
- RNA and protein synthesis mechanisms
- Nerve injury and regeneration
- Epilepsy research and treatment
- Spinal Cord Injury Research
- Nicotinic Acetylcholine Receptors Study
- Photoreceptor and optogenetics research
- RNA regulation and disease
- Viral Infections and Immunology Research
- Cardiovascular Effects of Exercise
- Memory and Neural Mechanisms
- Neural dynamics and brain function
- Neonatal and fetal brain pathology
- Neurogenesis and neuroplasticity mechanisms
- Tissue Engineering and Regenerative Medicine
- Cardiomyopathy and Myosin Studies
- Pericarditis and Cardiac Tamponade
- Congenital heart defects research
- Photochromic and Fluorescence Chemistry
Carilion Roanoke Memorial Hospital
2024
Biomedical Research Institute
2021-2024
Virginia Tech
2018-2024
Virginia–Maryland College of Veterinary Medicine
2018-2024
Carilion Clinic
2018-2024
Emory University
2012-2023
Northwestern University
2021
MRC Laboratory of Molecular Biology
2021
Vanderbilt University
2021
National University of Singapore
2021
This study evaluates functional recovery after transplanting human bone marrow-derived stromal cells (BMSCs) into contusion models of spinal cord injury (SCI). The authors used a high-throughput process to expand BMSCs and characterized them by flow cytometry, ELISA, gene expression. They found that secrete neurotrophic factors cytokines with therapeutic potential for cell survival axon growth. In adult immune-suppressed rats, mild, moderate, or severe contusions were generated using the...
N-methyl-D-aspartate receptors (NMDARs), ligand-gated ionotropic glutamate receptors, play key roles in normal brain development and various neurological disorders. Here we use standing variation data from the human population to assess which protein domains within NMDAR GluN1, GluN2A GluN2B subunits show strongest signal for being depleted of missense variants. We find that this includes GluN2 pre-M1 helix linker between agonist-binding domain (ABD) first transmembrane (M1). then evaluate...
Microglia, the resident immune cells of central nervous system, exist in either a "resting" state associated with physiological tissue surveillance or an "activated" neuroinflammation. We recently showed that ATP is primary chemoattractor to damage vivo and elicits opposite effects on motility activated microglia vitro through activation adenosine A2A receptors. However, whether systemic inflammation affects microglial responses remains largely unknown. Using two-photon imaging mice, we show...
Polymicrogyria is a malformation of cortical development. The aetiology polymicrogyria remains poorly understood. Using whole-exome sequencing we found de novo heterozygous missense GRIN1 mutations in 2 57 parent-offspring trios with polymicrogyria. We nine further additional patients. Shared features the patients were extensive bilateral associated severe developmental delay, postnatal microcephaly, visual impairment and intractable epilepsy. encodes GluN1, essential subunit...
Developing cortical GABAergic interneurons rely on genetic programs, neuronal activity, and environmental cues to construct inhibitory circuits during early postnatal development. Disruption of these events can cause long-term changes in inhibition may be involved neurological disorders associated with circuit dysfunction. We hypothesized that tonic glutamate signaling the neonatal cortex contributes to, is necessary for, maturation interneurons. To test this hypothesis, we used mice both...
BACKGROUND: Viral cardiac infection represents a significant clinical challenge encompassing several etiological agents, disease stages, complex presentation, and resulting lack of mechanistic understanding. Myocarditis is major cause sudden death in young adults, where current knowledge the field dominated by later phases pathological immune responses. However, little known regarding how can acutely induce an arrhythmogenic substrate before Adenovirus leading myocarditis, but due to species...
Object. Stem cell therapy has been shown to have considerable therapeutic potential for spinal cord injuries (SCIs); however, most experiments in animals performed by injecting cells directly into the injured parenchyma. This invasive technique compromises cord, although it delivers hostile environment of acutely cord. In this study, authors tested possibility delivering stem using three different minimally techniques. Methods. Bone marrow stromal (BMSCs) are clinically attractive because...
Cell transplantation as a treatment for spinal cord injury is promising therapeutic strategy whose effective clinical application would be facilitated by non-invasive delivery protocols. Cells derived from the bone marrow are particularly attractive because they can obtained easily, expanded to large numbers and potentially used autologous well allogeneic transplantation. In this study we tested feasibility of novel minimally invasive method--lumbar puncture (LP)--for transplanting stromal...
Abstract Uncovering the mechanisms that regulate dendritic spine morphology has been limited, in part, by lack of efficient and unbiased methods for analyzing spines. Here, we describe an automated 3D morphometry method its application to remodeling live neurons abnormalities a disease model. We anticipate this approach will advance studies synapse structure function brain development, plasticity, disease.
Communication among neurons is mediated through synaptic connections between axons and dendrites, most excitatory synapses occur on actin-rich protrusions along dendrites called dendritic spines. Dendritic spines are structurally dynamic, synapse strength closely correlated with spine morphology. Abnormalities in the size, shape, number of prevalent neurologic diseases, including autism spectrum disorders, schizophrenia, Alzheimer disease. However, therapeutic targets that influence...
NMDA receptors are tetrameric complexes of GluN1, GluN2A-D, and GluN3A-B subunits involved in normal brain function neurologic disorders. We identified a novel class stereoselective pyrrolidinone (PYD) positive allosteric modulators for GluN2C-containing receptors, exemplified by methyl 4-(3-acetyl-4-hydroxy-1-[2-(2-methyl-1<i>H</i>-indol-3-yl)ethyl]-5-oxo-2,5-dihydro-1<i>H</i>-pyrrol-2-yl)benzoate. Here we explore the site mechanism action prototypical analog, PYD-106, which at 30 <i>μ</i>M...
The GluN2D subunit of the NMDA receptor is prominently expressed in basal ganglia and associated brainstem nuclei, including subthalamic nucleus (STN), globus pallidus, striatum, substantia nigra. However, little known about how GluN2D-containing receptors contribute to synaptic activity these regions. Using Western blotting STN tissue punches, we demonstrated that rat throughout development [age postnatal day 7 (P7)–P60] adult (age P120). Immunoelectron microscopy brain showed predominantly...
N-methyl-D-aspartate receptors (NMDARs) mediate slow excitatory postsynaptic transmission in the central nervous system, thereby exerting a critical role neuronal development and brain function. Rare genetic variants GRIN genes encoding NMDAR subunits segregated with neurological disorders. Here, we summarize clinical presentations for 18 patients harboring 12 de novo missense GRIN1, GRIN2A, GRIN2B that alter residues M2 re-entrant loop, region lines pore is intolerant to variation. These...
Thalamocortical network dysfunction contributes to seizures and sleep deficits in Dravet syndrome (DS), an infantile epileptic encephalopathy, but the underlying molecular cellular mechanisms remain elusive. DS is primarily caused by mutations SCN1A gene encoding voltage-gated sodium channel NaV1.1, which highly expressed GABAergic reticular thalamus (nRT) neurons as well glutamatergic thalamocortical neurons. We hypothesized that NaV1.1 haploinsufficiency alters somatosensory...
N-Methyl-d-aspartate receptors (NMDARs) are ionotropic glutamate that mediate excitatory synaptic transmission and have been implicated in numerous neurological disorders. NMDARs typically comprise two GluN1 GluN2 subunits. The four subtypes (GluN2A-GluN2D) distinct functional properties gene expression patterns, which contribute to diverse roles for the brain. Here, we present a series of GluN2C/2D-selective negative allosteric modulators built around N-aryl benzamide (NAB) core....