A5056302090- Mitochondrial Function and Pathology
- Genomics and Rare Diseases
- Metabolism and Genetic Disorders
- CRISPR and Genetic Engineering
- RNA and protein synthesis mechanisms
- MicroRNA in disease regulation
- Neurobiology and Insect Physiology Research
- Insect symbiosis and bacterial influences
- Machine Learning in Bioinformatics
- Ubiquitin and proteasome pathways
- Biochemical and Molecular Research
- Gene expression and cancer classification
- NF-κB Signaling Pathways
- Circular RNAs in diseases
- Neurogenetic and Muscular Disorders Research
- Amyotrophic Lateral Sclerosis Research
- RNA Interference and Gene Delivery
- Genomics and Phylogenetic Studies
- Muscle Physiology and Disorders
- Colorectal Cancer Surgical Treatments
- Evolution and Genetic Dynamics
- Advanced Proteomics Techniques and Applications
- Silk-based biomaterials and applications
- Ion Channels and Receptors
- Lysosomal Storage Disorders Research
Oklahoma Medical Research Foundation
2020-2024
Baylor College of Medicine
2012-2018
Howard Hughes Medical Institute
2014-2018
Neurological Research Institute
2016
Johns Hopkins University
2011-2012
Johns Hopkins Medicine
2011
Chungnam National University
1995-2010
Chungnam National University Hospital
2004
Yonsei University
2000
ATP synthase, H+ transporting, mitochondrial F1 complex, δ subunit (ATP5F1D; formerly ATP5D) is a of synthase and plays an important role in coupling proton translocation production. Here, we describe two individuals, each with homozygous missense variants ATP5F1D, who presented episodic lethargy, metabolic acidosis, 3-methylglutaconic aciduria, hyperammonemia. Subject 1, for c.245C>T (p.Pro82Leu), recurrent decompensation starting the neonatal period, subject 2, c.317T>G (p.Val106Gly),...
The antiapoptotic function of NF-κB is believed to be mediated through the induction genes. Among genes, cellular inhibitor apoptosis protein 2 (c-IAP2/HIAP-1/MIHC) originally identified as a molecule recruited tumor necrosis factor (TNF) receptor complex, and its expression preferentially up-regulated by TNF other stimuli activating NF-κB. However, direct evidence transcriptional regulation on c-IAP2 gene still missing. Here, we have cloned characterized promoter region required for...
Recent studies have identified both recessive and dominant forms of mitochondrial disease that result from ATAD3A variants. The form includes subjects with biallelic deletions mediated by non-allelic homologous recombination. We report five unrelated neonates a lethal metabolic disorder characterized cardiomyopathy, corneal opacities, encephalopathy, hypotonia, seizures in whom monoallelic reciprocal duplication at the ATAD3 locus was identified. Analysis breakpoint junction fragment...
Abstract Background ATPase family AAA-domain containing protein 3A (ATAD3A) is a nuclear-encoded mitochondrial membrane-anchored involved in diverse processes including dynamics, DNA organization, and cholesterol metabolism. Biallelic deletions (null), recessive missense variants (hypomorph), heterozygous or duplications (antimorph) ATAD3A lead to neurological syndromes humans. Methods To expand the mutational spectrum of provide functional interpretation alleles trans deletion alleles, we...
Abstract Aberrant cholesterol metabolism causes neurological disease and neurodegeneration, mitochondria have been linked to perturbed homeostasis via the study of pathological mutations in ATAD3 gene cluster. However, whether changes were compensatory or contributory disorder was unclear, effects on cell membranes wider also unknown. Using patient-derived cells, we show that perturbation is a conserved feature variants accompanied by an expanded lysosome population containing membrane...
The CRISPR-Cas9 system has enabled researchers to precisely modify/edit the sequence of a genome. A typical editing experiment consists two steps: (1) cultured cells; (2) cell cloning and selection clones with without intended edit, presumed be isogenic. application may result in off-target edits, whereas will reveal culture-acquired mutations. We analyzed extent former latter by whole genome sequencing three experiments involving separate genomic loci conducted independent laboratories. In...
Protein phosphorylation occurs in certain sequence/structural contexts that are still incompletely understood. The amino acids surrounding the phosphorylated residues important determining binding of kinase to protein sequence. Upon these sequences also determine domains specifically bind sequences. Thus far, such 'motifs' have been identified through alignment a limited number well substrates. RESULTS: Experimentally determined sites from Human Reference Database were used identify 1,167...
Activation of protein kinase C (PKC) by phorbol 12-myristate 13-acetate (PMA) triggers cellular signals that lead to the activation transcription factor NF-kappaB (nuclear kappaB) in various cell types. In addition short-time PMA treatment, here we report prolonged exposure human colonic cancer epithelial cells treated with can also a persistent inhibition activation. selectively causes degradation IkappaB kinases (IKKs) including IKK-gamma and IKK-beta, subsequent tumor necrosis (TNF)...
Four mutations in the VAMP/synaptobrevin-associated protein B (VAPB) gene have been linked to amyotrophic lateral sclerosis (ALS) type 8. The mechanism by which VAPB cause motor neuron disease is unclear, but studies of most common P56S variant suggest both loss function and dominant-negative sequestration wild-type protein. Diminished levels its proteolytic cleavage fragment also reported sporadic ALS cases, suggesting that may be a disease. Here, we tested whether neuronal overexpression...
Comparison of the Efficacy Oral Capecitabine versus Bolus 5-FU in Preoperative Radiotherapy Locally Advanced Rectal CancerThe effects treatment with oral capecitabine vs. bolus 5-FU, administered concurrently preoperative radiotherapy, were compared locally advanced rectal cancer (LARC).One hundred and twenty-seven patients LARC received concurrent chemoradiation using two cycles (500 mg/m 2 /day) plus leucovorin (LV, 20 (Group I).Another group 1,650 /day LV II, 97 patients).Radiation was...
Angiogenesis is critical and indispensable for tumor progression. Since VEGF known to play a central role in angiogenesis, the disruption of VEGF-VEGF receptor system promising target anti-cancer therapy. Previously, we reported that hexapeptide (RRKRRR, RK6) blocked growth metastasis by inhibiting binding its receptors. In addition, dRK6, D-form derivative RK6, retained biological activity with improved serum stability. present study, developed serum-stable branched dimeric peptide...
In this protocol, we take CRISPR/Cas9 and Gal4/UAS approaches to achieve tissue-specific knockout in parallel with rescue of the by cDNA expression Drosophila. We demonstrate that guide RNAs targeting exon-intron junction target genes cleave genomic locus genes, but not UAS-cDNA transgenes, a tissue where Gal4 drives Cas9 expression. The efficiency approach enables determination pathogenicity disease-associated variants human manner For complete details on use execution please refer Yap et...
This study aimed to establish the genetic cause of a novel autosomal recessive neurodevelopmental disorder characterized by global developmental delay, movement disorder, and metabolic abnormalities.We performed detailed clinical characterization 4 unrelated individuals from consanguineous families with disorder. We used exome sequencing or targeted-exome sequencing, cosegregation, in silico protein modeling, functional analyses variants HEK293 cells Drosophila melanogaster, as well...
Mutations in the nuclear matrix protein Matrin 3 ( MATR3 ) have been identified amyotrophic lateral sclerosis and myopathy. To investigate mechanisms underlying mutations neuromuscular diseases efficiently screen for modifiers of toxicity, we generated transgenic flies. Our findings indicate that expression wild‐type or mutant motor neurons reduces climbing ability lifespan flies, while their indirect flight muscles (IFM) results abnormal wing positioning muscle degeneration. In both IFM,...
As advanced sequencing technologies continue to uncover an increasing number of variants in genes associated with human genetic diseases, there is a growing demand for systematic approaches assess the impact these on development, health, and disease.While silico analyses have provided valuable insights, it essential complement findings model organism studies determine functional consequences vivo.Drosophila melanogaster excellent such due its efficient technologies, high gene conservation...