A5002109010- Retinal Diseases and Treatments
- Genetics and Neurodevelopmental Disorders
- Genomics and Rare Diseases
- Retinal Imaging and Analysis
- RNA modifications and cancer
- RNA Research and Splicing
- Lipid metabolism and disorders
- Epigenetics and DNA Methylation
- Advanced Glycation End Products research
- Fetal and Pediatric Neurological Disorders
- Pancreatic function and diabetes
- Angiogenesis and VEGF in Cancer
- Neuroinflammation and Neurodegeneration Mechanisms
- Diabetes and associated disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Sphingolipid Metabolism and Signaling
- Ubiquitin and proteasome pathways
- Atherosclerosis and Cardiovascular Diseases
- RNA regulation and disease
- Natural Antidiabetic Agents Studies
- Prenatal Screening and Diagnostics
- RNA and protein synthesis mechanisms
- Glaucoma and retinal disorders
- Retinal Development and Disorders
- Autism Spectrum Disorder Research
Translational Genomics Research Institute
2015-2024
Phoenix (United States)
2024
University of Alabama at Birmingham
2022
Fondazione Santa Lucia
2021
Inserm
2021
University of California, Los Angeles
2020
University of Southern California
2020
University of Iowa
2020
Columbia University
2020
Providence Sacred Heart Medical Center
2020
Most anti-vascular endothelial growth factor (VEGF) therapies in diabetic macular edema are not as robust proliferative retinopathy. Although the VEGF appears to be a good target edema, anti-VEGF appear of transient benefit recurs within few weeks, and repeated injections necessary. There is new evidence that indicates 'retinal inflammation' an important player pathogenesis common sets inflammatory cytokines upregulated both serum vitreous aqueous samples, subjects with retinopathy, these...
Inflammation in the diabetic retina is mediated by leukocyte adhesion to retinal vasculature and alteration of blood-retinal barrier (BRB). We investigated role chemokines BRB diabetes. Animals were made streptozotocin injection analyzed for gene expression monocyte/macrophage infiltration. The CCL2 (chemokine ligand 2) was significantly up-regulated retinas rats with 4 8 weeks diabetes also human endothelial cells treated high glucose flux. Additionally, or intraocular recombinant resulted...
OBJECTIVE—Zinc transporter eight (SLC30A8) is a major target of autoimmunity in human type 1A diabetes and implicated 2 genome-wide association studies. The nonsynonymous single nucleotide polymorphism (SNP) affecting aa325 lies within the region highest ZnT8 autoantibody (ZnT8A) binding, prompting an investigation its relationship to 1 diabetes. RESEARCH DESIGN AND METHODS—ZnT8A radioimmunoprecipitation assays were performed 421 new-onset diabetic Caucasians using COOH-terminal constructs...
Although VEGF has been identified as an important mediator of the blood-retinal barrier alteration in diabetic retinopathy, hypothesis for this study was that other molecules, including angiopoietins (Ang-1 and -2), may play a role. The expression analyzed animal model role Ang-2 regulation diabetes-induced alterations vascular permeability characterized.Diabetes induced rats, human retinal endothelial cells (HRECs) were grown media with 5.5 or 30.5 mM glucose. Levels Ang-1 -2 mRNA protein...
Abstract Aminoacyl tRNA synthetases (ARSs) link specific amino acids with their cognate transfer RNAs in a critical early step of protein translation. Mutations ARSs have emerged as cause recessive, often complex neurological disease traits. Here we report an allelic series consisting seven novel and two previously reported biallelic variants valyl-tRNA synthetase ( VARS ) ten patients developmental encephalopathy microcephaly, associated early-onset epilepsy. In silico, vitro, yeast...
Abstract The robust detection of disease-associated splice events from RNAseq data is challenging due to the potential confounding effect gene expression levels and often limited number patients with relevant data. Here we present a novel statistical approach splicing outlier differential analysis. Our tests for differences in percentages sequence reads representing local events. We describe software package called Bisbee which can predict protein-level alterations, key feature lacking many...
Rett syndrome is an acquired progressive neurodevelopmental disorder caused by
Objective— The mechanisms that regulate the physical interaction of pericytes and endothelial cells effects these interactions on interendothelial cell junctions are not well understood. We determined extent to which vascular could pericyte-endothelial adhesion consequences this disruption might have function barrier. Methods Results— Human retinal microvascular were cocultured with pericytes, effect monolayer resistance expression junction molecules N-cadherin VE-cadherin measured....
<ns4:p>Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutation in the X-linked <ns4:italic>MECP2</ns4:italic> gene, encoding methyl-CpG-binding protein 2. We have created mouse model (<ns4:italic>Mecp2</ns4:italic> A140V “knock-in” mutant) expressing recurrent human linked to an mental retardation/Rett phenotype. Morphological analyses focused on quantifying soma and nucleus size were performed primary hippocampus cerebellum granule neuron (CGN) cultures from mutant...
<ns4:p>Mutations disrupting presynaptic<ns4:italic> </ns4:italic>protein TBC1D24 are associated with a variable neurological phenotype, including DOORS syndrome, myoclonic epilepsy, early-infantile epileptic encephalopathy, and non-syndromic hearing loss. In this report, we describe family segregating autosomal dominant 37-year-old Caucasian female severe phenotype Parkinsonism, psychosis, visual auditory hallucinations, gait ataxia intellectual disability. Whole exome sequencing revealed...
KIF26B is a member of the kinesin superfamily with evolutionarily conserved functions in controlling aspects embryogenesis, including development nervous system, though its function incompletely understood. We describe an infant progressive microcephaly, pontocerebellar hypoplasia, and arthrogryposis secondary to involvement anterior horn cells ventral (motor) nerves. performed whole exome sequencing on trio identified de novo missense variant, p.Gly546Ser, proband. This variant alters...
Abstract The sodium-leak channel NALCN forms a subthreshold sodium conductance that controls the resting membrane potentials of neurons. auxiliary subunits and their functions in mammals are largely unknown. In this study, we demonstrate two large proteins UNC80 UNC79 complex. knockout mice neonatal lethal. C-terminus contains domain interacts with overcomes soma-retention signal to achieve dendritic localization. lacking domain, as found human patients, still supports whole-cell currents...