A5034436231- Osteoarthritis Treatment and Mechanisms
- Cancer-related molecular mechanisms research
- Inflammatory mediators and NSAID effects
- MicroRNA in disease regulation
- Celiac Disease Research and Management
- Circular RNAs in diseases
- Cytokine Signaling Pathways and Interactions
- Cancer-related gene regulation
- RNA Research and Splicing
- Helicobacter pylori-related gastroenterology studies
- Cell Adhesion Molecules Research
- Microscopic Colitis
- Autoimmune Bullous Skin Diseases
- Extracellular vesicles in disease
- Galectins and Cancer Biology
- Genetic Associations and Epidemiology
- RNA modifications and cancer
- Bone Metabolism and Diseases
- Mesenchymal stem cell research
- Gastrointestinal disorders and treatments
- Connective Tissue Growth Factor Research
- Wnt/β-catenin signaling in development and cancer
- Bone and Joint Diseases
- Thyroid Disorders and Treatments
- Urticaria and Related Conditions
Leiden University Medical Center
2017-2024
European Space Research and Technology Centre
2024
Leiden University
2018-2023
Universidade Federal do Paraná
2016-2021
University Medical Center Groningen
2011-2016
University of Groningen
2011-2016
RMIT University
2013
Universidade de Brasília
2008-2013
Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants 11 osteoarthritis phenotypes, 52 of which have not been the disease before. We report thumb spine differences in genetic effects between weight-bearing non-weight-bearing joints. sex-specific early age-at-onset loci. integrate functional genomics data from...
Objective To uncover the microRNA (miRNA) interactome of osteoarthritis (OA) pathophysiological process in cartilage. Methods We performed RNA sequencing 130 samples (n=35 and n=30 pairs for messenger (mRNA) miRNA, respectively) on macroscopically preserved lesioned OA cartilage from same patient differential expression (DE) analysis miRNA mRNAs. build an OA-specific interactome, a prioritisation scheme was applied based inverse Pearson’s correlations DE miRNAs Subsequently, these were...
Back pain is a common and debilitating disorder with largely unknown underlying biology. Here we report genome-wide association study of back using diagnoses assigned in clinical practice; dorsalgia (119,100 cases, 909,847 controls) intervertebral disc (IDD) (58,854 922,958 controls). We identify 41 variants at 33 loci. The most significant (OR
Objectives In osteoarthritis, methylation of lysine 79 on histone H3 (H3K79me), a protective epigenetic mechanism, is reduced. Histone levels are dynamically regulated by methyltransferases and demethylases. Here, we aimed to identify which demethylases regulate H3K79me in cartilage investigate whether their targeting protects against osteoarthritis. Methods We determined demethylase expression human non-osteoarthritis osteoarthritis using qPCR. The role families subfamilies was interrogated...
Although genome-wide association studies and fine mapping have identified 39 non-HLA loci associated with celiac disease (CD), it is difficult to pinpoint the functional variants susceptibility genes in these loci. We applied integrative approaches annotate prioritize single nucleotide polymorphisms (SNPs), pathways affected CD. CD-associated SNPs were intersected regulatory elements categorized by ENCODE project variants, while results from cis-expression quantitative trait (eQTL) 1469...
MicroRNAs derived from extracellular vesicles (EV-miRNAs) are circulating miRNAs considered as potential new diagnostic markers for cancer that can be easily detected in liquid biopsies. In this study, we performed RNA sequencing analysis a screening strategy to identify EV-miRNAs serum of clinically well-annotated breast (BC) patients the south Brazil. EVs three groups samples (healthy controls (CT), luminal A (LA), and triple-negative (TNBC)) were isolated using precipitation method...
To evaluate the possible association between celiac disease (CD) and/or gluten sensitivity (GS) and autism spectrum disorder (ASD).Occurrences of CD were determined in a group children adolescents affected by ASD and, conversely, occurrences assessed biopsy-proven patients. detect existence GS, levels antigliadin antibodies patients compared with non-celiac children.The prevalence or GS was not greater than groups originating from same geographical area. Similarly patients.No statistically...
To identify key determinants of the interactive pathophysiologic processes in subchondral bone and cartilage osteoarthritis (OA).We performed RNA sequencing on macroscopically preserved lesional OA from patients Research Arthritis Articular Cartilage study who underwent joint replacement surgery due to (n = 24 sample pairs: 6 hips 18 knees). Unsupervised hierarchical clustering differential expression analyses were conducted. Results combined with data previously identified differentially...
// Bruna Sugita 1 , Mandeep Gill 2 Akanskha Mahajan Anju Duttargi Saurabh Kirolikar Rodrigo Almeida Kenny Regis Olusayo L. Oluwasanmi Fabio Marchi 3 Catalin Marian 4, 8 Kepher Makambi 2, 5 Bhaskar Kallakury 6 Laura Sheahan 7 Iglenir J. Cavalli Enilze M. Ribeiro Subha Madhavan Simina Boca Yuriy Gusev Luciane R. Department of Genetics, Federal University Paraná, Curitiba, PR, Brazil Oncology, Lombardi Comprehensive Cancer Center, Georgetown Medical Washington, DC, USA International Research...
Osteoarthritis is a complex degenerative joint disease. Here, we investigate matched genotype and methylation profiles of primary chondrocytes from macroscopically intact (low-grade) degraded (high-grade) osteoarthritis cartilage synoviocytes collected 98 osteoarthritis-affected individuals undergoing knee replacement surgery. We perform an epigenome-wide association study degeneration report robustly replicating markers, which reveal etiologic mechanism linked to the migration epithelial...
Abstract Osteoarthritis is a prevalent joint disease and major cause of disability worldwide with no curative therapy. Development disease-modifying therapies requires better understanding the molecular mechanisms underpinning disease. A hallmark osteoarthritis cartilage degradation. To define events characterizing at whole transcriptome level, we performed deep RNA sequencing in paired samples low- high-osteoarthritis grade knee derived from 124 patients undergoing total replacement. We...
Background Despite recent advances in the understanding of genetic architecture osteoarthritis (OA), only two loci have been identified for OA hand, part explained by complexity different hand joints and heterogeneity pathology. Methods We used data from Rotterdam Study (RSI, RSII RSIII) to create three phenotypes based on clustering patterns radiographic severity increase power our modest discovery genome-wide association studies RS (n=8700), sought replication an independent cohort,...
Failing of intrinsic chondrocyte repair after mechanical stress is known as one the most important initiators osteoarthritis. Nonetheless, insight into these early mechano-pathophysiological processes in age-related human articular cartilage still lacking. Such insights are needed to advance clinical development. To highlight molecular osteoarthritis mechano-pathology, transcriptome-wide changes following injurious on aged osteochondral explants were characterized.Following at a strain 65%...
Objective To identify robustly differentially expressed long noncoding RNAs (lncRNAs) with osteoarthritis (OA) pathophysiology in cartilage and to explore potential target messenger RNA (mRNA) by establishing coexpression networks, followed functional validation. Methods sequencing was performed on macroscopically lesioned preserved OA from patients who underwent joint replacement surgery due (n = 98). Differential expression analysis lncRNAs that were annotated GENCODE Ensembl databases....
To identify OA subtypes based on cartilage transcriptomic data in tissue and characterize their underlying pathophysiological processes and/or clinically relevant characteristics.This study includes n = 66 primary patients (41 knees 25 hips), who underwent a joint replacement surgery, from which macroscopically unaffected (preserved, 56) lesioned (n 45) articular were collected [Research Arthritis Articular Cartilage (RAAK) study]. Unsupervised hierarchical clustering analysis preserved...