A5018732153- Interstitial Lung Diseases and Idiopathic Pulmonary Fibrosis
- Immune Cell Function and Interaction
- HIV Research and Treatment
- T-cell and B-cell Immunology
- Sphingolipid Metabolism and Signaling
- Asthma and respiratory diseases
- Systemic Sclerosis and Related Diseases
- Fibroblast Growth Factor Research
- IL-33, ST2, and ILC Pathways
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Medical Imaging and Pathology Studies
- Hippo pathway signaling and YAP/TAZ
- Neonatal Respiratory Health Research
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- Optical Coherence Tomography Applications
- Chemokine receptors and signaling
- Cell Adhesion Molecules Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Allergic Rhinitis and Sensitization
- Pulmonary Hypertension Research and Treatments
- Endoplasmic Reticulum Stress and Disease
- Reproductive System and Pregnancy
- Kruppel-like factors research
Massachusetts General Hospital
2014-2023
Harvard University
2013-2023
Northwestern University
2022
Pulmonary and Critical Care Associates
2002-2020
Ragon Institute of MGH, MIT and Harvard
2012-2019
American Thoracic Society
2017
University of Michigan
2017
RELX Group (United States)
2017
University of Chicago
2014
Center for Rheumatology
2002-2013
Tissue stiffening is a hallmark of fibrotic disorders but has traditionally been regarded as an outcome fibrosis, not contributing factor to pathogenesis. In this study, we show that fibrosis induced by bleomycin injury in the murine lung locally increases median tissue stiffness sixfold relative normal parenchyma. Across pathophysiological range, cultured fibroblasts transition from surprisingly quiescent state progressive proliferation and matrix synthesis, accompanied coordinated...
Pathological fibrosis is driven by a feedback loop in which the fibrotic extracellular matrix both cause and consequence of fibroblast activation. However, molecular mechanisms underlying this process remain poorly understood. Here we identify yes-associated protein (YAP) (homolog drosophila Yki) transcriptional coactivator with PDZ-binding motif (TAZ) (also known as Wwtr1), effectors Hippo pathway, key stiffness-regulated coordinators activation synthesis. YAP TAZ are prominently expressed...
Mutations in sarcomere protein genes can cause hypertrophic cardiomyopathy (HCM), a disorder characterized by myocyte enlargement, fibrosis, and impaired ventricular relaxation. Here, we demonstrate that gene mutations activate proliferative profibrotic signals non-myocyte cells to produce pathologic remodeling HCM. Gene expression analyses of isolated from HCM mouse hearts showed increased levels RNAs encoding cell-cycle proteins, Tgf-β, periostin, other proteins. Markedly BrdU labeling,...
Numerous compounds have shown efficacy in limiting development of pulmonary fibrosis using animal models, yet few these replicated beneficial effects clinical trials. Given the challenges associated with performing trials patients idiopathic (IPF), it is imperative that preclinical data packages be robust their analyses and interpretations to best chance selecting promising drug candidates advance The American Thoracic Society has convened a group experts lung discuss formalize...
Genital Chlamydia trachomatis (Ct) infection induces protective immunity that depends on interferon-γ-producing CD4 T cells. By contrast, we report mucosal exposure to ultraviolet light (UV)-inactivated Ct (UV-Ct) generated regulatory cells exacerbated subsequent infection. We show immunization with UV-Ct complexed charge-switching synthetic adjuvant particles (cSAPs) elicited long-lived protection in conventional and humanized mice. UV-Ct-cSAP targeted immunogenic uterine CD11b(+)CD103(-)...
The generation of humanized BLT mice by the cotransplantation human fetal thymus and liver tissues CD34(+) cells into nonobese diabetic/severe combined immunodeficiency allows for long-term reconstitution a functional immune system, with T cells, B dendritic monocytes/macrophages repopulating mouse tissues. Here, we show that sustained high-level disseminated virus (HIV) infection, resulting in CD4(+) T-cell depletion generalized activation. Following HIV-specific humoral responses were...
Section:ChooseTop of pageAbstract <<Biology Alveolar Injur...Role ECMPreclinical ModelingThe Role Inflammation ...Genetic, Epigenetic, and ...Translation Discoverie...SummaryReferencesCITING ARTICLES
Persistent myofibroblast activation distinguishes pathological fibrosis from physiological wound healing, suggesting that therapies selectively inducing apoptosis could prevent progression and potentially reverse established in diseases such as scleroderma, a heterogeneous autoimmune disease characterized by multiorgan fibrosis. We demonstrate fibroblast-to-myofibroblast differentiation driven matrix stiffness increases the mitochondrial priming (proximity to apoptotic threshold) of these...
Pharmacologic stimulation of a G protein–coupled receptor preferentially expressed on fibroblasts reverses experimental lung and liver fibrosis.
Cerebral malaria is a significant cause of global mortality, causing an estimated two million deaths per year, mainly in children. The pathogenesis this disease remains incompletely understood. Chemokines have been implicated the development cerebral malaria, and IFN-inducible CXCR3 chemokine ligand IP-10 (CXCL10) was recently found to be only serum biomarker that predicted mortality Ghanaian We show ligands Mig (CXCL9) were highly induced brains mice with murine caused by Plasmodium berghei...
Studies to define the overall contribution of lymphocytes lesion formation in atherosclerosis-susceptible mice have demonstrated relatively subtle effects; use lymphocyte-deficient mice, however, compromises both effector and regulatory arms immune system. Here, we tested hypothesis that deletion CXCL10 (IP-10), a chemokine specific for T cells has been localized within atherosclerotic lesions, would significantly inhibit atherogenesis.Compound deficient Apoe(-/-)/Cxcl10(-/-) fed...
Neutrophil recruitment into tissue plays an important role in host defense and disease pathogenesis, including the inflammatory arthritides. A multitude of diverse chemoattractants have been implicated neutrophil recruitment, suggesting that they overlapping functions mediating this critical biological response. However, here we demonstrate a unique, non-redundant for leukotriene B4 receptor BLT1 joint K/BxN mouse model arthritis. We expression was absolutely required arthritis generation...
The continued spread of the HIV epidemic underscores need to interrupt transmission. One attractive strategy is a topical vaginal microbicide. Sexual transmission herpes simplex virus type 2 (HSV-2) in mice can be inhibited by intravaginal siRNA application. To overcome challenges knocking down gene expression immune cells susceptible infection, we used chimeric RNAs composed an aptamer fused for targeted knockdown bearing aptamer-binding receptor. Here, showed that CD4 aptamer-siRNA...