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One or more keywords matched the following properties of Boyce, Joshua
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overview The overall goal of my lab is to apply principals of pathophysiology of allergic diseases in humans to questions at the bench, and in turn to bring fundamental findings made at the bench back to the clinic. The dominant themes include how lipid mediators and their receptors function in a network to control the development and activation of mast cells, a central cell type in the effector phases of all allergic diseases. We defined the growth factor requirements for the development of human mast cells from their earliest progenitors, and identified a key role for interleukin (IL)-4 as an accessory mitogen. Human mast cells exposed to IL-4 become competent to generate leukotriene C4 (LTC4) the precursor of the powerful bronchoconstrictor LTD4 and the stable metabolite LTE4. This competence is due to the induced expression of LTC4 synthase, the requisite terminal enzyme involved in LTC4 synthesis. These observations explain why mucosal inflammation elicits a mast cell hyperplasia accompanied by strikingly increased regional concentrations of LTC4 LTD4 and LTE4. We discovered that the growth potentiating effect of IL-4 depended on the induction of LTC4S, and the transactivation of the c-kit tyrosine kinase by the type 1 receptor for cys-LTs (CysLT1R). We also demonstrated that CysLT1R on mast cells exists as a heterodimer with the type 2 receptor for cys-LTs (CysLT2R), and that the latter is a potent negative regulator of the former. Most recently, we discovered that LTE4 only a weak agonist of CysLT1R and CysLT2R, is the most potent member of this mediator class for causing chemokine generation by mast cells and potentiating pulmonary inflammation in mice. These actions are due to the purinergic receptor P2Y12, which we have shown to be the long-elusive third cys-LT receptor. We plan to translate these observations into the clinic, and will test the efficacy of a P2Y12 antagonist on clinical reactions to aspirin challenge in aspirin-intolerant asthmatic individuals as a major goal of a U19 funded by NIAID.
One or more keywords matched the following items that are connected to Boyce, Joshua
Item TypeName
Academic Article Cysteinyl leukotriene overproduction in aspirin-exacerbated respiratory disease is driven by platelet-adherent leukocytes.
Concept Aspirin
Concept Asthma, Aspirin-Induced
Academic Article Pathogenesis of aspirin-exacerbated respiratory disease and reactions.
Academic Article Prostaglandin E2 deficiency causes a phenotype of aspirin sensitivity that depends on platelets and cysteinyl leukotrienes.
Academic Article Prostaglandin E2 Resistance in Granulocytes from Patients with Aspirin Exacerbated Respiratory Disease
Academic Article Prostaglandin E2 resistance in granulocytes from patients with aspirin-exacerbated respiratory disease.
Academic Article Prostaglandin D2: a dominant mediator of aspirin-exacerbated respiratory disease.
Academic Article Impaired E Prostanoid2 Expression and Resistance to Prostaglandin E2 in Nasal Polyp Fibroblasts from Subjects with Aspirin-Exacerbated Respiratory Disease.
Academic Article Platelet-driven leukotriene C4-mediated airway inflammation in mice is aspirin-sensitive and depends on T prostanoid receptors.
Academic Article Platelets in patients with aspirin-exacerbated respiratory disease.
Academic Article Aspirin-Exacerbated Respiratory Disease Involves a Cysteinyl Leukotriene-Driven IL-33-Mediated Mast Cell Activation Pathway.
Academic Article Aspirin-Exacerbated Respiratory Disease--New Prime Suspects.
Academic Article Thymic stromal lymphopoietin controls prostaglandin D2 generation in patients with aspirin-exacerbated respiratory disease.
Grant Chemical Mediators of Acute Pulmonary Disorders
Grant Eicosanoid Networks in Aspirin Exacerbated Respiratory Disease
Grant Lipidomic and Transcriptome Signatures in Aspirin-Exacerbated Respiratory Disease
Grant Pathophysiologic and Therapeutic Mechanisms of Aspirin Exacerbated Respiratory Disease
Academic Article Aspirin-exacerbated respiratory disease: Mediators and mechanisms of a clinical disease.
Grant Eicosanoid Networks in Aspirin Hypersensitivity
Academic Article Type 2 Cysteinyl Leukotriene Receptors Drive IL-33-Dependent Type 2 Immunopathology and Aspirin Sensitivity.
Academic Article A trial of type 12 purinergic (P2Y12) receptor inhibition with prasugrel identifies a potentially distinct endotype of patients with aspirin-exacerbated respiratory disease.
Academic Article COX-1 mediates IL-33-induced extracellular signal-regulated kinase activation in mast cells: Implications for aspirin sensitivity.
Academic Article Plasma tryptase elevation during aspirin-induced reactions in aspirin-exacerbated respiratory disease.
Academic Article Cysteinyl leukotriene receptor 2 drives lung immunopathology through a platelet and high mobility box 1-dependent mechanism.
Academic Article Unique Effect of Aspirin Therapy on Biomarkers in Aspirin-exacerbated Respiratory Disease. A Prospective Trial.
Academic Article Aspirin sensitivity: Lessons in the regulation (and dysregulation) of mast cell function.
Academic Article IL-5Ra marks nasal polyp IgG4- and IgE-expressing cells in aspirin-exacerbated respiratory disease.
Search Criteria
  • Aspirin
Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.