A5014177046- Bone Metabolism and Diseases
- Respiratory viral infections research
- Systemic Sclerosis and Related Diseases
- Bone health and treatments
- NF-κB Signaling Pathways
- IL-33, ST2, and ILC Pathways
- Rheumatoid Arthritis Research and Therapies
- Immune Response and Inflammation
- Asthma and respiratory diseases
- Signaling Pathways in Disease
- Osteoarthritis Treatment and Mechanisms
- Neonatal Respiratory Health Research
- Pneumonia and Respiratory Infections
- Viral gastroenteritis research and epidemiology
- Knee injuries and reconstruction techniques
- Immunodeficiency and Autoimmune Disorders
- Cardiac electrophysiology and arrhythmias
- Eosinophilic Disorders and Syndromes
- Bone and Joint Diseases
- Thermoregulation and physiological responses
- Immune Cell Function and Interaction
- Body Composition Measurement Techniques
- Cell death mechanisms and regulation
- Musculoskeletal synovial abnormalities and treatments
- T-cell and B-cell Immunology
Merck & Co., Inc., Rahway, NJ, USA (United States)
2018-2024
Flagship Pioneering (United States)
2022-2023
Boston University
2019
Harvard University
2009-2018
Brigham and Women's Hospital
2008-2017
University Hospitals of Cleveland
2013
University School
2013
Case Western Reserve University
2013
Ragon Institute of MGH, MIT and Harvard
2010
New York University
1994-2001
Apoptosis is implicated in the generation and resolution of inflammation response to bacterial pathogens. All pathogens produce lipoproteins (BLPs), which trigger innate immune response. BLPs were found induce apoptosis THP-1 monocytic cells through human Toll-like receptor–2 (hTLR2). also initiated an epithelial cell line transfected with hTLR2. In addition, stimulated nuclear factor–κB, a transcriptional activator multiple host defense genes, activated respiratory burst Thus, hTLR2...
Significance New interventions are needed to improve bone health and reduce the risk for osteoporosis fracture. Dysbiosis is increasingly linked metabolic abnormalities, although effect of microbiota on skeletal poorly understood. Previous studies suggest detrimental by increasing resorption. In this report, we show that gut resident promote formation, as well resorption, with long-term exposure resulting in net growth. Microbiota induce hormone insulin-like growth factor 1 (IGF-1), which...
Osteoporosis results from an imbalance in skeletal remodeling that favors bone resorption over formation. Bone matrix is degraded by osteoclasts, which differentiate myeloid precursors response to the cytokine RANKL. To gain insight into transcriptional regulation of during growth and disease, we generated a conditional knockout transcription factor nuclear activated T cells c1 (Nfatc1). Deletion Nfatc1 young mice resulted osteopetrosis inhibition osteoclastogenesis vivo vitro....
Abstract Local delivery of therapeutics for the treatment inflammatory arthritis (IA) is limited by short intra-articular half-lives. Since IA severity often fluctuates over time, a local drug method that titrates release to activity would represent an attractive paradigm in therapy. Here we report development hydrogel platform exhibits disassembly and controlled concentration enzymes expressed during flares. In vitro, loaded with triamcinolone acetonide (TA) releases on-demand upon exposure...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTObservation of Catalytic Intermediates in the Suzuki Reaction by Electrospray Mass SpectrometryAntonios O. Aliprantis and James W. CanaryCite this: J. Am. Chem. Soc. 1994, 116, 15, 6985–6986Publication Date (Print):July 1, 1994Publication History Published online1 May 2002Published inissue 1 July 1994https://pubs.acs.org/doi/10.1021/ja00094a083https://doi.org/10.1021/ja00094a083research-articleACS PublicationsRequest reuse permissionsArticle...
The pathophysiology of the most common joint disease, osteoarthritis (OA), remains poorly understood. Since synovial fluid (SF) bathes cartilage and synovium, we reasoned that a comparative analysis its protein constituents in health OA could identify pathways involved damage. We undertook this study to perform proteomic knee SF from patients control subjects compare results microarray expression data synovium.Age-matched samples 10 subjects, with early-stage OA, late-stage were compared...
Patients taking immunosuppressive drugs, like cyclosporine A (CsA), that inhibit calcineurin are highly susceptible to disseminated fungal infections, although it is unclear how these drugs suppress resistance opportunistic pathogens. We show in a mouse model of Candida albicans infection, CsA-induced susceptibility infection maps the innate immune system. To further define cell types targeted by CsA, we generated mice with conditional deletion B (CnB) neutrophils. These displayed markedly...
Increased osteoclastic bone resorption leads to periarticular erosions and systemic osteoporosis in RA patients. Although a great deal is known about how osteoclasts differentiate from precursors resorb bone, the identity of an osteoclast precursor (OCP) population vivo its regulatory role remains elusive. Here, we report identification CD11b–/loLy6Chi BM with OCP activity vitro vivo. These cells, which can be distinguished previously characterized myeloid lineage, display features both M1...
Mice bearing a "humanized" immune system are valuable tools to experimentally manipulate human cells in vivo and facilitate disease models not normally possible laboratory animals. Here we describe form of GVHD that develops NOD/SCID mice reconstituted with fetal bone marrow, liver thymus (NS BLT mice). The skin, lungs, gastrointestinal tract parotid glands affected progressive inflammation sclerosis. Although all showed involvement at least one organ site, the incidence overt clinical was...
Objective Proinflammatory molecules promote osteoclast‐mediated bone erosion by up‐regulating local RANKL production. However, recent evidence suggests that combinations of cytokines, such as tumor necrosis factor (TNF) plus interleukin‐6 (IL‐6), induce RANKL‐independent osteoclastogenesis. The purpose this study was to better understand TNF/IL‐6–induced osteoclast formation and determine whether RANK is absolutely required for osteoclastogenesis in murine inflammatory arthritis. Methods...
Respiratory Syncytial Virus (RSV) causes lower respiratory tract infections that can be severe and sometimes fatal. The risk for RSV infection is highest in infants older adults. A safe effective vaccine adults represents a serious unmet medical need due to higher morbidity mortality this age group. In randomized, partially double-blind, placebo-controlled, phase 1 dose-escalation study, we evaluated the safety, tolerability immunogenicity of an investigational messenger ribonucleic acid...
Shigella flexneri, an etiological agent of bacillary dysentery, causes apoptosis in vitro. Here we show that it also induces vivo. We were able to quantify the number apoptotic cells rabbit Peyer's patches infected with S. flexneri by detecting fragmented DNA. Infection virulent results massive numbers within lymphoid follicles. In contrast, neither avirulent strain nor capable colonizing increases background level cells. Macrophages, T cells, and B are shown undergo These indicate may play...
Tissue remodeling with fibrosis is a predominant pathophysiological mechanism of many human diseases. Systemic sclerosis rare, often lethal, disorder unknown etiology manifested by dermal (scleroderma) and excessive connective tissue deposition in internal organs. Currently, there are no available antifibrotic therapeutics, reflection our lack understanding this process. Animal models scleroderma useful tools to dissect the transcription factors cytokines that govern fibrosis. A...
Over the past decade and a half, biomedical community has uncovered previously unappreciated reciprocal relationship between cells of immune skeletal systems. Work in this field, which been termed "osteoimmunology," resulted development clinical therapeutics for seemingly disparate diseases linked by common themes inflammation bone remodeling. Here, important concepts discoveries osteoimmunology are discussed context bridging these two organ systems, including arthritis, osteoporosis,...
Development of personalized treatment regimens is hampered by lack insight into how individual animal models reflect subsets human disease, and autoimmune inflammatory conditions have proven resistant to such efforts. Scleroderma a lethal disease characterized fibrosis, with no effective therapy. Comparative gene expression profiling showed that murine sclerodermatous graft-versus-host (sclGVHD) approximates an subset scleroderma estimated at 17% 36% patients analyzed diffuse, 28% limited,...
There are few treatment options for symptomatic knee osteoarthritis (OA). Human amniotic suspension allografts (ASA) have anti-inflammatory and chondroregenerative potential thus represent a promising strategy. In anticipation of large, placebo-controlled trial intra-articular ASA OA, an open-label prospective feasibility study was performed. Six patients with Kellgren–Lawrence grades 3 4 tibiofemoral OA were administered single injection containing cryopreserved particulated human amnion...
Significance Currently, little is understood about how the transcriptional regulation of cartilage breakdown contributes to pathogenesis osteoarthritis (OA). Here, we report that, within cartilage, transcription factor Nuclear activated T cells c1 (NFATc1) displays selective expression in superficial articular chondrocytes. Accordingly, mice lacking both NFATc1 and NFATc2 were generated found develop a severe, spontaneous early-onset OA. These findings establish as key repressor...
Clesrovimab (MK-1654) is an investigational, half-life extended human monoclonal antibody (mAb) against RSV F glycoprotein in clinical trials as a prophylactic agent infection for infants.This adult study measured clesrovimab concentrations the serum and nasal epithelial lining fluid (ELF) to establish partitioning of after dosing. ELF were normalized sampling dilution using urea from serum. Furthermore, vitro neutralization following dosing was also examine activity compartment.mAbs with...