A5019866571- Bone Metabolism and Diseases
- Bone health and osteoporosis research
- Bone health and treatments
- Rheumatoid Arthritis Research and Therapies
- Bone and Joint Diseases
- Spondyloarthritis Studies and Treatments
- Cytokine Signaling Pathways and Interactions
- Systemic Lupus Erythematosus Research
- Orthopaedic implants and arthroplasty
- Hip and Femur Fractures
- Monoclonal and Polyclonal Antibodies Research
- Bone fractures and treatments
- Genetics, Aging, and Longevity in Model Organisms
- Osteoarthritis Treatment and Mechanisms
- Inflammasome and immune disorders
- Immune Response and Inflammation
- Protein Kinase Regulation and GTPase Signaling
- MicroRNA in disease regulation
- Nutrition and Health in Aging
- Vitamin K Research Studies
- Chronic Myeloid Leukemia Treatments
- Biomarkers in Disease Mechanisms
- RNA Research and Splicing
- Immunodeficiency and Autoimmune Disorders
- Frailty in Older Adults
Blueprint Medicines (United States)
2024-2025
Harvard University
2015-2022
Boston Children's Hospital
2015-2022
Orthopaedic Research Laboratories
2017-2020
University of Lisbon
2009-2018
Instituto de Medicina Molecular João Lobo Antunes
2009-2014
Hospital de Santa Maria
2011-2014
Center for Rheumatology
2014
Instituto de Medicina Tropical
2010-2013
Instituto de Medicina Genómica
2013
Abstract We recently developed base editing, a genome-editing approach that enables the programmable conversion of one pair into another without double-stranded DNA cleavage, excess stochastic insertions and deletions, or dependence on homology-directed repair. The application editing is limited by off-target activity reliance intracellular delivery. Here we describe two advances address these limitations. First, greatly reduce installing mutations our third-generation editor (BE3) to...
Objective. To characterize circulating B-cell subpopulations of arthritis patients with <6 weeks disease duration. Methods. Peripheral blood samples were collected from very early untreated polyarthritis patients, duration, for flow cytometric evaluation subpopulations. Samples who later diagnosed as RA [very (VERA)] also 4–6 after starting a low dose prednisone (5–10 mg) and 4 months reaching the minimum effective MTX. A matched healthy group was used control. Results. VERA have lower...
Background Fracture healing is orchestrated by a specific set of events that culminates in the repair bone and reachievement its biomechanical properties. The aim our work was to study sequence gene expression involved inflammation remodeling occurring early phases callus formation osteoporotic patients. Methodology/Principal Findings Fifty-six patients submitted hip replacement surgery after low-energy fracture were enrolled this study. grouped according time interval between surgery:...
Evolution is replete with reuse of genes in different contexts, leading to multifunctional roles signaling factors during development. Here, we explore osteoclast regulation skeletal development through analysis colony-stimulating factor 1 receptor (csf1r) function the zebrafish. A primary role Csf1r regulate proliferation, differentiation and myelomonocytic cells, including osteoclasts. We demonstrate retention two functional paralogues csf1r Mutant indicates that have shared, non-redundant...
The association of non-MHC genes with AS has been recently suggested. We aimed to investigate the ERAP1, IL23R and TNFSF15 regions susceptibility protection from in HLA-B27-positive individuals.A total 200 unrelated patients 559 healthy subjects, all HLA-B27 positive, were tested. Twenty single nucleotide polymorphisms (SNPs) investigated near (nine SNPs), ERAP1 (five SNPs) (six SNPs).ERAP1 rs30187 [odds ratio (OR) = 1.5, P 4.7 × 10(-3)] had strongest susceptibility. A protective effect was...
Introduction: Systemic mastocytosis (SM) is a rare, clonal hematologic neoplasm driven by the KIT D816V mutation in ~95% of cases. SM spectrum diseases including advanced (AdvSM) and its subgroups aggressive (ASM), with an associated (SM-AHN), mast cell leukemia (MCL), as well indolent (ISM). Avapritinib, highly selective inhibitor, approved for treatment adult patients (pts) ISM AdvSM. Bone disease measurable changes (e.g. T-score, Z-score) bone density (BD), assessed dual-energy X-ray...
Abstract The objective of this study was to assess whether clinical measures rheumatoid arthritis activity and severity were influenced by tumor necrosis factor-alpha ( TNF-α ) promoter genotype/haplotype markers. Each patient's disease assessed the score using 28 joint counts (DAS28) functional capacity Health Assessment Questionnaire (HAQ) score. Systemic manifestations, radiological damage evaluated Sharp/van der Heijde (SvdH) score, disease-modifying anti-rheumatic drug use, surgeries,...
A small but important group of patients in our lupus cohort has needed total joint replacement (TJR). Arthritis was identified 94% patients. We have determined how many TJR, explored the risk factors for this procedure with SLE and reviewed outcome these Records who attended clinic at University College London Hospital/Middlesex from 1978 to 2008 were underwent TJR identified. recorded demographic data, other major systemic manifestations SLE, autoantibody profile, previous use steroids,...
Abstract Introduction In this study we used a mice model of chronic arthritis to evaluate if bone fragility induced by inflammation is associated with an imbalance in turnover and also disorganization the type I collagen network. Methods Serum, vertebrae femur bones were collected from eight-month-old polyarthritis SKG controls. Strength femoral was evaluated using three-point bending tests density assessed pycnometer. Bone markers carboxy-terminal cross-linking telopeptides (CTX-I)...
Objective. Tumor necrosis factor (TNF) increases circulating osteoclast (OC) precursors numbers by promoting their proliferation and differentiation. The aim of this study was to assess the effect TNF inhibitors (TNFi) on differentiation activity OC in rheumatoid arthritis (RA) patients. Methods. Seventeen RA patients treated with TNFi were analyzed at baseline after a minimum follow-up period 6 months. Blood samples collected receptor activator nuclear kappa-B ligand (RANKL) surface...
Ankylosing spondylitis (AS) is a chronic inflammatory disease in which genetic factors play central role. The efficacy of TNF blockers has reoriented research this field order to explain the influence AS pathogenesis. objective study was access single nucleotide polymorphisms (SNPs) at positions –308 and –238 promoter region gene on susceptibility prognosis. SNPs were determined by restriction fragment length patients controls. exhibited decreased frequency A allele position (10%) when...
Objective. Considering the relevance of tumor necrosis factor-α (TNF-α) in pathophysiology juvenile idiopathic arthritis (JIA), it is likely that polymorphisms its promoter area may be relevant disease susceptibility and activity. We investigated if clinical measures JIA activity TNF-α serum concentrations were associated with −308 genotypes. Methods. Portuguese patients 5 pediatric rheumatology centers recruited consecutively, along a control group healthy subjects. Demographic data blood...
Ankylosing spondylitis (AS) is typically characterized by focal bone overgrowth and also systemic loss. We hypothesize that the increased osteoproliferation found in AS might be partially due to reduced ability of osteoclast precursors (OCPs) differentiate into osteoclasts (OCs). Therefore, our aim was characterize remodeling pro-osteoclastogenesis inflammatory environment, monocytes' phenotype, vitro differentiation patients. Patients with active without any ongoing therapy age-...
Objective. Rheumatoid arthritis (RA) is associated with higher levels of inflammatory mediators and a more atherogenic lipid profile. Dyslipidemia can be present years before develops. Lymphotoxin-α (LTA) cytokine that mediates proinflammatory responses while also participating in homeostasis, its transcriptional activity part genetically determined. We examined the role single-nucleotide polymorphism at position 252 LTA gene genetic background RA dyslipidemia. Methods. The association...
Introduction Ankylosing Spondylitis (AS) is characterized by excessive local bone formation and concomitant systemic loss. Tumor necrosis factor (TNF) plays a central role in the inflammation of axial skeleton enthesis AS patients. Despite reduction loss, patients treated with TNF inhibitors (TNFi) have ongoing formation. The aim this study was to assess effect TNFi differentiation activity osteoclasts (OC) Methods 13 were analyzed at baseline after minimum follow-up period 6 months. 25...
Inactivating mutations in the ubiquitously expressed membrane trafficking component GMAP-210 (encoded by Trip11) cause achondrogenesis type 1A (ACG1A). ACG1A is surprisingly tissue specific, mainly affecting cartilage development. Bone development also abnormal, but as chondrogenesis and osteogenesis are closely coupled, this could be a secondary consequence of defect. A possible explanation for specificity that bone highly secretory tissues with high use machinery. The perinatal lethality...