A5016673842- Genetic Neurodegenerative Diseases
- Tryptophan and brain disorders
- 3D Printing in Biomedical Research
- Mitochondrial Function and Pathology
- Pluripotent Stem Cells Research
- DNA Repair Mechanisms
- Neurological disorders and treatments
- Stress Responses and Cortisol
- Genomic variations and chromosomal abnormalities
- Biomedical and Engineering Education
- Genetics and Neurodevelopmental Disorders
- Biomedical Ethics and Regulation
- Neuroendocrine regulation and behavior
- RNA and protein synthesis mechanisms
- Advanced Proteomics Techniques and Applications
- Bipolar Disorder and Treatment
- Chromosomal and Genetic Variations
- Cancer-related Molecular Pathways
- Genomics and Chromatin Dynamics
- Extracellular vesicles in disease
- Neuroscience and Neural Engineering
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Prenatal Screening and Diagnostics
- Biomedical Text Mining and Ontologies
National Institutes of Health
2015-2025
National Center for Advancing Translational Sciences
2015-2025
National Institute of Neurological Disorders and Stroke
1997-2018
University of Liverpool
2016
Office of the Director
2016
National Cancer Institute
1997-2011
Brookhaven National Laboratory
2009
National Institute of Dental and Craniofacial Research
2009
National Human Genome Research Institute
1996-2005
Florida College
2004
A gene, ATM , that is mutated in the autosomal recessive disorder ataxia telangiectasia (AT) was identified by positional cloning on chromosome 11q22-23. AT characterized cerebellar degeneration, immunodeficiency, chromosomal instability, cancer predisposition, radiation sensitivity, and cell cycle abnormalities. The disease genetically heterogeneous, with four complementation groups have been suspected to represent different genes. which has a transcript of 12 kilobases, found be patients...
Niemann-Pick type C (NP-C) disease, a fatal neurovisceral disorder, is characterized by lysosomal accumulation of low density lipoprotein (LDL)–derived cholesterol. By positional cloning methods, gene ( NPC1) with insertion, deletion, and missense mutations has been identified in NP-C patients. Transfection fibroblasts wild-type NPC1 cDNA resulted correction their excessive storage LDL cholesterol, thereby defining the critical role regulation intracellular cholesterol trafficking. The...
An integrated human-mouse positional candidate approach was used to identify the gene responsible for phenotypes observed in a mouse model of Niemann-Pick type C (NP-C) disease. The predicted murine NPC1 protein has sequence homology putative transmembrane domains Hedgehog signaling molecule Patched, cholesterol-sensing regions 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and SREBP cleavage-activating (SCAP), orthologs identified human, nematode Caenorhabditis elegans , yeast...
Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency radiation sensitivity, and cancer predisposition. A-T heterozygotes are moderately prone. The gene, designated ATM, was recently identified in our laboratory by positional cloning, a partial cDNA clone found to encode polypeptide with PI-3 kinase domain. We report here the molecular cloning of contig spanning complete open reading frame ATM gene. predicted protein 3056 amino...
The purpose of our study was to determine the relationship between mutant huntingtin (Htt) and mitochondrial dynamics in progression Huntington's disease (HD). We measured mRNA levels electron transport chain genes, structural Drp1 (dynamin-related protein 1), Fis1 (fission Mfn1 (mitofusin Mfn2 2), Opa1 (optric atrophy Tomm40 (translocase outermembrane 40) CypD (cyclophilin D) grade III IV HD patients controls. Htt oligomers proteins were quantified striatum frontal cortex patients. Changes...
The regular workshops held by the Center for Alternatives to Animal Testing (CAAT) on biology-inspired microphysiological systems (MPS) taking place every four years, have become a reliable measure assess fundamental scientific, industrial and regulatory trends translational science in MPS-field from bird's eye view. 2023 workshop participants at that time concluded technology as used within academia has matured significantly, underlined broad use of MPS steadily increasing number high...
Patients with the genetic disorder ataxia telangiectasia (AT) have mutations in AT mutated (ATM) gene, which is homologous to TEL1 and checkpoint gene MEC1. A tel1 deletion mutant, unlike a mec1 deletion, viable does not exhibit increased sensitivity DNA-damaging agents. However, dosage of rescues mec1-1, agents viability disruption. mec1-1 delta 1 double mutants are synergistically sensitive agents, including radiomimetic drugs. These data indicate that MEC1 functionally related functions...
Neurons in Huntington's disease exhibit selective morphological and subcellular alterations the striatum cortex. The link between these neuronal changes behavioral abnormalities is unclear. We investigated relationships essential that predict motor impairment possible involvement of corticostriatal pathway developing phenotypes. therefore generated heterozygote mice expressing N-terminal one-third huntingtin with normal (CT18) or expanded (HD46, HD100) glutamine repeats. HD exhibited...
Infertility is a common feature of the human disorder ataxia-telangiectasia and Atm-deficient mice are completely infertile. To gain further insight into role ATM in meiosis, we examined meiotic cells during development. Spermatocyte degeneration begins between postnatal days 8 16.5, soon after entry prophase I while oocytes degenerate late embryogenesis prior to dictyate arrest. Using electron microscopy immunolocalization proteins mutant adult spermatocytes, found that male female...
Tissue- and developmental stage-specific expression of the human beta-like globin genes is regulated by a combination ubiquitous erythroid-restricted trans factors that bind to cis elements near each five active genes. Additional interactions these with sequences located in far 5' end cluster occur as yet obscure mechanisms. Because complexity this regulatory puzzle, precise identification determinants control hemoglobin switching has proven difficult. Phylogenetic footprinting an...
The National Institutes of Health Microphysiological Systems (MPS) program, led by the Center for Advancing Translational Sciences, is part a joint effort on MPS development with Defense Advanced Research Projects Agency and regulatory guidance from FDA, now in its final year funding. program has produced many tangible outcomes tissue chip terms stem cell differentiation, microfluidic engineering, platform development, single multi-organ systems—and continues to help facilitate acceptance...
The product of the ataxia-telangiectasia gene (ATM) was identified by using an antiserum developed to a peptide corresponding deduced amino acid sequence. ATM protein is single, high-molecular weight predominantly confined nucleus human fibroblasts, but present in both nuclear and microsomal fractions from lymphoblast cells peripheral blood lymphocytes. levels localization remain constant throughout all stages cell cycle. Truncated not detected lymphoblasts patients homozygous for mutations...