A5026922049- Genetics and Neurodevelopmental Disorders
- MicroRNA in disease regulation
- Lipoproteins and Cardiovascular Health
- Autism Spectrum Disorder Research
- Cancer-related molecular mechanisms research
- Epigenetics and DNA Methylation
- Antiplatelet Therapy and Cardiovascular Diseases
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Chromatin Remodeling and Cancer
- Immune Cell Function and Interaction
- Olfactory and Sensory Function Studies
- Erythrocyte Function and Pathophysiology
- Diabetes Management and Research
- Drug Transport and Resistance Mechanisms
- Inflammatory mediators and NSAID effects
- Neuroendocrine Tumor Research Advances
- Cardiac Valve Diseases and Treatments
- Systemic Lupus Erythematosus Research
- Pancreatic function and diabetes
- Animal Behavior and Welfare Studies
- Genetic Syndromes and Imprinting
- Atherosclerosis and Cardiovascular Diseases
- Chromosomal and Genetic Variations
- Genomic variations and chromosomal abnormalities
- Advanced biosensing and bioanalysis techniques
AstraZeneca (United States)
2021-2023
Horizon Therapeutics (United States)
2022
Jacksonville Center for Clinical Research
2021
National Institute of Dental and Craniofacial Research
2013-2016
National Institutes of Health
2014-2016
Center for Cancer Research
2011
Hebrew University of Jerusalem
2005-2009
AbstractDisruptions in the expression of Bdnf gene that encodes a neurotrophic factor involved neuronal survival, differentiation and synaptic plasticity has been proposed to contribute molecular pathogenesis Rett syndrome. syndrome (RTT) is neurodevelopmental disorder, caused by mutations X-linked methyl CpG binding protein 2 (MeCP2). MeCP2 deficiency brain shown decrease overall spite an observed increase activity promoter III appears be controlled directly MeCP2. Therefore, how causes...
Rett syndrome (RS) is a severe and progressive neurodevelopmental disorder caused by heterozygous mutations in the X-linked methyl CpG binding protein 2 (MeCP2) gene. MeCP2 nuclear that binds specifically to methylated DNA functions as general transcription repressor context of chromatin remodeling complexes. RS shares clinical features with those Angelman (AS), an imprinting disorder. In AS patients, maternally expressed copy UBE3A codes for ubiquitin ligase 3A (E6-AP) repressed. The...
Background Blockade of the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a potentially attractive mechanism for lowering inflammatory and lipid risk in patients with atherosclerosis. This study aims to assess safety, tolerability, target engagement MEDI6570, high-affinity monoclonal blocking antibody LOX-1. Methods Results phase 1, first-in-human, placebo-controlled (NCT03654313) randomized 88 type 2 diabetes receive single ascending doses (10, 30, 90, 250, or 500 mg)...
We analysed the genomic organisation of miR-153, a microRNA embedded in genes that encode two major type 1 diabetes autoantigens, islet-associated protein (IA)-2 and IA-2β. also identified miR-153 target correlated with IA-2β localisation function. A bioinformatics approach was used to identify miR-153's organisation. To analyse co-regulation IA-2β, quantitative PCR analysis Ia-2β (also known as Ptprn2) performed after glucose stimulation assay MIN6B cells isolated murine pancreatic islets,...
High mobility group N1 protein (HMGN1), a nucleosomal-binding that affects the structure and function of chromatin, is encoded by gene located on chromosome 21 overexpressed in Down syndrome, one most prevalent genomic disorders. Misexpression HMGN1 cellular transcription profile; however, biological this still not fully understood. We report modulates expression methyl CpG-binding 2 (MeCP2), DNA-binding known to affect neurological functions including autism spectrum disorders, whose...
Islet antigen (IA)-2, IA-2β, and glutamate decarboxylase (GAD65) are major autoantigens in type 1 diabetes (T1D). Autoantibodies to these appear years before disease onset widely used as predictive markers. Little is known, however, about what regulates the expression of autoantigens. The present experiments were initiated test hypothesis that microRNAs (miRNAs) can target affect levels Bioinformatics was identify miRNAs predicted mRNAs coding IA-2, GAD65. RNA interference for miRNA...
Background MEDI6012 is recombinant human lecithin cholesterol acyltransferase, the rate-limiting enzyme in reverse transport. Infusions of acyltransferase have potential to enhance transport and benefit patients with coronary heart disease. The purpose this study was test safety, pharmacokinetic, pharmacodynamic profile MEDI6012. Methods Results This phase 2a double-blind randomized 48 subjects stable disease on a statin single dose or placebo (6:2) (NCT02601560) ascending doses administered...
Background: High-density lipoprotein plays a key role in reverse cholesterol transport. In addition, high-density particles may be cardioprotective and reduce infarct size the setting of myocardial injury. Lecithin-cholesterol acyltransferase is rate-limiting enzyme MEDI6012 recombinant human lecithin-cholesterol that increases cholesterol. Administration has potential to regress coronary plaque acute ST-segment–elevation infarction. Methods: REAL-TIMI 63B (A Randomized, Placebo‑controlled...
Reverse cholesterol transport (RCT) removes and stabilizes vulnerable plaques. In addition, high-density lipoprotein (HDL) may be cardioprotective in acute myocardial infarction (MI). Lecithin-cholesterol acyltransferase (LCAT) enhance RCT. The objective of this study was to investigate the pharmacokinetics, pharmacodynamics, safety multiple ascending doses recombinant human LCAT (MEDI6012) inform a Phase 2b programme.This randomized, blinded, placebo-controlled, dose-escalation 2a MEDI6012....
Small cell lung cancers (SCLC) are tumors of neuroendocrine origin. Previous in vitro studies from our laboratory showed that SCLC expresses high levels the transmembrane dense core vesicle protein IA-2 (islet antigen-2) as compared to normal cells. IA-2, through its effect on vesicles (DCVs), is known be involved secretion hormones and neurotransmitters. It believed dysregulated release neurotransmitter Acetylcholine (ACh) by DCVs has an autocrine growth. Recently, we found a target...
Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by dominant mutation in the X-linked methyl CpG binding protein 2 (MeCP2) gene. Neuroanatomically, RTT characterized reduction dendritic arborization and perikaryal size brain. MECP2 binds methylated promoters facilitates assembly of multiprotein repressor complex that includes Sin3A histone deacetylases HDAC1/HDAC2. MeCP2 has recently been found to be downregulated autistic spectrum disorders such as Angelman (AS) RTT, which...