A5066431511- RNA and protein synthesis mechanisms
- RNA modifications and cancer
- Complement system in diseases
- Platelet Disorders and Treatments
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Blood Coagulation and Thrombosis Mechanisms
- COVID-19 Clinical Research Studies
- Genomics and Phylogenetic Studies
- Monoclonal and Polyclonal Antibodies Research
- Hemoglobinopathies and Related Disorders
- Genomics and Rare Diseases
- Machine Learning in Bioinformatics
- SARS-CoV-2 and COVID-19 Research
- Adipose Tissue and Metabolism
- Biosensors and Analytical Detection
- Adipokines, Inflammation, and Metabolic Diseases
- Advanced Proteomics Techniques and Applications
- Signaling Pathways in Disease
- Renal Diseases and Glomerulopathies
- Virus-based gene therapy research
- Mechanical Circulatory Support Devices
- Fungal and yeast genetics research
- Viral Infectious Diseases and Gene Expression in Insects
- Atherosclerosis and Cardiovascular Diseases
Center for Biologics Evaluation and Research
2015-2024
United States Food and Drug Administration
2011-2024
Michigan State University
2022
MedStar Georgetown University Hospital
2022
Georgetown University
2022
King's College London
2021
Riverside Methodist Hospital
2016
Doctors Hospital
2016
Grant Medical Center
2016
St. Boniface Hospital
2011
<h3>Background</h3> Haemophilia B is caused by genetic aberrations in the <i>F9</i> gene. The majority of these are non-synonymous mutations that alter primary structure blood coagulation factor IX (FIX). However, a synonymous mutation c.459G>A (Val107Val) was clinically reported to result mild haemophilia (FIX coagulant activity 15%–20% normal). mRNA patients showed no skipping or retention introns and/or change levels, suggesting integrity does not contribute origin disease affected...
Abstract Synonymous codons occur with different frequencies in organisms, a phenomenon termed codon usage bias. Codon optimization, common term for variety of approaches used widely by the biopharmaceutical industry, involves synonymous substitutions to increase protein expression. It had long been presumed that variants, which, definition, do not alter primary amino acid sequence, have no effect on structure and function. However, critical mass reports suggests variations may impact...
Intravascular sickling and lysis of red blood cells, a hallmark feature sickle cell disease (SCD), releases hemoglobin (Hb) into the circulation. Increased cell-free Hb has been linked to vasculopathy in vitro lipid oxidation. Scavenger plasma proteins haptoglobin (Hp) hemopexin (Hpx) can attenuate total heme lipid-oxidative capacity but are depleted SCD. Here, we isolated lipids from BERK-SS mice, guinea pigs (GP) infused with heme-albumin, patients SCD undergoing regular exchange...
Mutational analysis is commonly used to support the diagnosis and management of haemophilia. This has allowed for generation large mutation databases which provide unparalleled insight into genotype-phenotype relationships. Haemophilia associated with inversions, deletions, insertions, nonsense missense mutations. Both synonymous non-synonymous mutations influence base pairing messenger RNA (mRNA), can alter mRNA structure, cellular half-life ribosome processivity/elongation. However, role...
DAS resembles thousands of microphones along the sensing fiber. In railway applications, only a small fraction all data carries information about train-rail interaction. Transforming to rail view or train simplifies analysis and reveals valuable properties.
Thrombosis is a recognized complication of Coronavirus disease 2019 (COVID-19) and often associated with poor prognosis. There well-recognized link between coagulation inflammation, however, the extent thrombotic events COVID-19 warrants further investigation. Poly(A) Binding Protein Cytoplasmic 4 (PABPC4), Serine/Cysteine Proteinase Inhibitor Clade G Member 1 (SERPING1) Vitamin K epOxide Reductase Complex subunit (VKORC1), which are all proteins linked to coagulation, have been shown...
Synonymous variants within coding regions may influence protein expression and function. We have previously reported increased levels ex vivo (~120% in comparison to wild-type) from a synonymous polymorphism variant, c.354G>A [p.P118P], of the ADAMTS13 gene, encoding plasma protease responsible for von Willebrand Factor (VWF) degradation. In current study, we investigated potential mechanism(s) behind this variant its effect on physico-chemical properties. Cell-free assays showed enhanced...
Coronavirus disease (COVID-19) and resulting restrictions have significantly impacted physical activity levels. However, objectively measured changes in levels among UK university students during lockdown are understudied. Using data collected via remote measurement technology from a mobile tracker, this study aimed to describe the longitudinal trajectories of following start at large university, investigate whether these varied according age, gender, ethnicity. Continuous for steps walked...
Coronavirus disease of 2019 (COVID-19) is the clinical manifestation respiratory infection caused by severe acute syndrome coronavirus 2 (SARS-CoV-2). While primarily recognized as a disease, it clear that COVID-19 systemic illness impacting multiple organ systems. One defining feature has been high incidence thrombotic events. The underlying processes and risk factors for occurrence events in remain inadequately understood. bacterial, viral or fungal infections are well to activate...
Abstract Background Gene expression is highly variable across tissues of multi-cellular organisms, influencing the codon usage tissue-specific transcriptome. Cancer disrupts gene pattern healthy tissue resulting in altered preferences. The topic changes as they relate to demand, and tRNA supply cancer growing interest. Methods We analyzed transcriptome-weighted pair based on Genome Atlas (TCGA) RNA-seq data from 6427 solid tumor samples 632 normal samples. This dataset represents 32 types...
Abstract Hemophilia B is a blood clotting disorder caused by deficient activity of coagulation factor IX (FIX). Multiple recombinant FIX proteins are currently approved to treat hemophilia B, and several gene therapy products being developed. Codon optimization frequently used technique in the pharmaceutical industry improve protein expression recoding coding sequence using multiple synonymous codon substitutions. The underlying assumption this that substitutions do not alter characteristics...
Genomes have different types of genetic variation, and many changes are assumed to be "silent" — that is, they no effect on biology, health, or fitness. A recent study shows it is not simple.
Abstract Background Pre‐mRNA splicing is a complex process requiring the identification of donor site, acceptor and branch point site with an adjacent polypyrimidine tract sequence. Splicing regulated by regulatory elements (SREs) both enhancer suppressor functions. Variants located in exonic regions can impact through dysregulation native splice sites, SREs, cryptic activation. While considered primary disease‐inducing mechanism synonymous variants, its contribution toward disease phenotype...
Background The zinc metalloprotease ADAMTS13 is a multidomain protein that cleaves von Willebrand Factor (VWF) and implicated in Thrombotic Thrombocytopenic Purpura (TTP) pathogenesis. Understanding the mechanism of this an important goal. Conformation sensitive antibodies have been used to monitor conformation decipher molecular proteins as well distinguish functional non-functional mutants. Methodology/Principal Findings We characterized several against ADAMTS13, both monoclonal...
The liver is the primary source of a large number plasma proteins and plays critical role in multiple biological processes. Inadequate oxygen supply characterizing various clinical settings such as transplantation exposes to hypoxic conditions. Studies assessing hypoxia-induced global translational changes are lacking. Here, we employed recently developed ribosome-profiling technique assess responses human hepatocytes exposed acute stress (1% O 2 ) for short term. In parallel, transcriptome...
ADAMTS13 is a secreted zinc metalloprotease expressed by various cell types. Here, we investigate its cellular pathway in endogenously expressing liver lines and after transient transfection with ADAMTS13. Besides compartmentalizations of the secretory system, detected an appreciable level endogenous within nucleus. A positively charged amino acid cluster (R-Q-R-Q-R-Q-R-R) present propeptide may act as nuclear localization signal (NLS). Fusing this NLS-containing region to eGFP greatly...