A5020375219- Pluripotent Stem Cells Research
- Alzheimer's disease research and treatments
- Amyotrophic Lateral Sclerosis Research
- Neuroinflammation and Neurodegeneration Mechanisms
- CRISPR and Genetic Engineering
- Genomics and Rare Diseases
- Neurogenesis and neuroplasticity mechanisms
- Immune cells in cancer
- Neurogenetic and Muscular Disorders Research
- Epigenetics and DNA Methylation
- 3D Printing in Biomedical Research
- Neonatal Respiratory Health Research
- TGF-β signaling in diseases
- Renal and related cancers
- RNA Interference and Gene Delivery
- Cancer Genomics and Diagnostics
- Bioinformatics and Genomic Networks
- RNA Research and Splicing
- Tissue Engineering and Regenerative Medicine
- Macrophage Migration Inhibitory Factor
- Single-cell and spatial transcriptomics
- Dementia and Cognitive Impairment Research
- Prenatal Screening and Diagnostics
- Congenital heart defects research
- Forensic and Genetic Research
The Ohio State University
2004-2024
Nationwide Children's Hospital
2012-2024
The Ohio State University Wexner Medical Center
2020-2024
Rasmussen College
2021-2022
Battelle
2012-2016
Cancer Genetics (United States)
2004-2005
Recent studies have shown the importance of dynamic tumor microenvironment (TME) in high-grade gliomas (HGGs). In particular, myeloid cells are known to mediate immunosuppression glioma; however, it is still unclear if play a role low-grade glioma (LGG) malignant progression. Here, we investigate cellular heterogeneity TME using single-cell RNA sequencing murine model that recapitulates progression LGG HGG. LGGs show increased infiltrating CD4
Stem cell-derived motor neurons (MNs) are increasingly utilized for modeling disease in vitro and developing cellular replacement strategies spinal cord injury diseases such as muscular atrophy (SMA) amyotrophic lateral sclerosis (ALS). Human embryonic stem cell (hESC) differentiation into MNs, which involves retinoic acid (RA) activation of the sonic hedgehog (SHH) pathway is inefficient requires up to 60 days develop MNs with electrophysiological properties. This prolonged process has...
Accumulating evidence suggests that adult hippocampal neurogenesis relies on the controlled and continued proliferation of neural progenitor cells (NPCs). With age, decreases through mechanisms remain unclear but are believed to involve changes in NPC microenvironment. Here, we provide brain is part regulated by astrocytes via Wnt signaling this cellular cross-talk modified aging brain, leading decreased NPCs. Furthermore, show regulate cell cycle acting expression levels survivin, a known...
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of the motor system. Recent work in rodent models ALS has shown that insulin-like growth factor-1 (IGF-1) slows progression when delivered at onset. However, IGF-1's mechanism action along neuromuscular axis remains unclear. In this study, symptomatic mice received IGF-1 through stereotaxic injection an IGF-1-expressing viral vector to deep cerebellar nuclei (DCN), region cerebellum with extensive brain stem and spinal...
Cerebral organoids (COs) are rapidly accelerating the rate of translational neuroscience based on their potential to model complex features developing human brain. Several studies have examined electrophysiological and neural network COs; however, no study has comprehensively investigated developmental trajectory properties in whole-brain COs correlated these with developmentally linked morphological cellular features. Here, we profiled neuroelectrical activities over span 5 months a...
Abstract Human middle temporal gyrus (MTG) is a vulnerable brain region in early Alzheimer’s disease (AD), but little known about the molecular mechanisms underlying this regional vulnerability. Here we utilize 10 × Visium platform to define spatial transcriptomic profile both AD and control (CT) MTG. We identify unique marker genes for cortical layers white matter, layer-specific differentially expressed (DEGs) human compared CT. Deconvolution of spots showcases significant difference...
Glioblastoma multiforme (GBM) is a highly lethal human cancer thought to originate from self-renewing and therapeutically-resistant population of glioblastoma stem cells (GSCs). The intrinsic mechanisms enacted by GSCs during 3D tumor formation, however, remain unclear, especially in the stages prior angiogenic/immunological infiltration. In this study, we performed deep characterization genetic, immune, metabolic profiles GBM organoids several patient-derived (GBMO). Despite being devoid...
Amyotrophic lateral sclerosis (ALS) is a fatal, progressive paralysis arising from the premature death of motor neurons. An inherited form caused by dominant mutation in ubiquitously expressed superoxide dismutase (SOD1). SOD1 mutant expression within neurons determinant onset and early disease, accumulation microglia accelerates disease progression. Muscle also likely primary source for toxicity, because retraction axons synaptic connections to muscle among earliest presymptomatic events....
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by motor neuron cell death in the cortex, brainstem, and spinal cord. Extensive efforts have been made to develop trophic factor-based therapies enhance survival; however, achievement of adequate therapeutic delivery all regions corticospinal tract has remained significant challenge. Here, we show that adeno-associated virus serotype 4 (AAV4)-mediated expression insulin-like growth factor-1 (IGF-1) or...
DNA-based methods for human identification principally rely upon genotyping of short tandem repeat (STR) loci. Electrophoretic-based techniques variable-length classification STRs are universally utilized, but limited in that they have relatively low throughput and do not yield nucleotide sequence information. High-throughput sequencing technology may provide a more powerful instrument identification, is currently validated forensic casework. Here, we present systematic method to perform...
Long interspersed nuclear element-1 (L1 or LINE-1) is a highly abundant mobile genetic element in both humans and mice, comprising almost 20% of each genome. L1s are silenced by several mechanisms, as their uncontrolled expression has the potential to induce genomic instability. However, paradoxically expressed at high levels differentiating neural progenitor cells. Using vitro vivo techniques modulate L1 expression, we report that play critical role human mouse brain development regulating...
Phosphatase and tensin homologue (PTEN) regulates cell growth survival through inhibition of the mammalian target rapamycin (MTOR) signalling pathway. Germline genetic variation PTEN is associated with autism, macrocephaly hamartoma tumour syndromes. The effect developmental somatic mutations on nervous system phenotypes not well understood, although brain mosaicism MTOR pathway genes an emerging cause cortical dysplasia epilepsy in paediatric population. Here we report two variants...
Abstract Variants in the AUTS2 gene are associated with a broad spectrum of neurological conditions characterized by intellectual disability, microcephaly, and congenital brain malformations. Here, we use human cerebral organoid model to investigate pathophysiology heterozygous de novo missense variant identified patient multiple impairments including primary microcephaly profound disability. Proband organoids exhibit reduced growth, deficits neural progenitor cell (NPC) proliferation...
The high-affinity copper transporter CTR1 is encoded by (SLC31A1), a gene locus for which no detailed genotype-phenotype correlations have previously been reported. We describe identical twin male infants homozygous novel missense variant NM_001859.4:c.284 G > A (p.Arg95His) in with distinctive autosomal recessive syndrome of infantile seizures and neurodegeneration, consistent profound central nervous system deficiency. used clinical, biochemical molecular methods to delineate the first...
Background Reprogramming human somatic cells to pluripotency represents a valuable resource for the development of in vitro based models disease and holds tremendous potential deriving patient-specific pluripotent stem cells. Recently, mouse neural (NSCs) have been shown capable reprogramming into state by forced expression Oct3/4 Klf4; however it has unknown whether this same strategy could apply NSCs, which would result more relevant modeling disease. Methodology Principal Findings Here,...
Emerging evidence suggests that the neurotransmitter acetylcholine (ACh) negatively regulates development of neuromuscular junction, but it is not clear if ACh exerts its effects exclusively through muscle receptors (AChRs). Here, we used genetic methods to remove AChRs selectively from muscle. Similar blocking biosynthesis, eliminating postsynaptic increased motor axon branching and expanded innervation territory, suggesting synaptic growth AChRs. However, in contrast agrin-deficient mice...
Research Article19 October 2017Open Access Transparent process iPhemap: an atlas of phenotype to genotype relationships human iPSC models neurological diseases Ethan W Hollingsworth Laboratory for Neural Stem Cells and Functional Neurogenetics, Division Neuroimmunology Multiple Sclerosis, The Ohio State University Wexner Medical Center, Columbus, OH, USA Departments Neurology Neuroscience, Search more papers by this author Jacob E Vaughn Josh C Orack Chelsea Skinner Jamil Khouri Sofia B...