Title Albert L. Sheffer Professor of Medicine in the Field of Allergic Disease Institution Brigham and Women's Hospital Address Brigham and Women's Hospital Smith Bldg, Rm 618 75 Francis St Boston MA 02115
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Title
Professor of Pediatrics
Institution
Massachusetts General Hospital
Biography
1981
Charlotte Fahey Award
1995 - 2000
Physician-Scientist Award (K08)
2012
Alpha Omega Alpha (Alumini Member)
2012
AAAAI Special Recognition Award
2021
Outstanding Service Award
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.
Research
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R01AI136041
(BOYCE, JOSHUA A)
Dec 4, 2017 - Nov 30, 2022
Eicosanoid Networks in Aspirin Hypersensitivity
Role: Principal Investigator
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R01HL136209
(PENN, RAYMOND B.)
Feb 1, 2017 - Jan 31, 2021
Optimizing EP receptor subtype targeting for asthma therapy
Role: Co-Principal Investigator
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R21AI115137
(BOYCE, JOSHUA A)
Dec 5, 2014 - Nov 30, 2016
Characterization of a Novel Growth and Survival Factor for Human Mast Cells
Role: Principal Investigator
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R01HL117945
(BOYCE, JOSHUA A)
Jun 15, 2013 - Apr 30, 2017
Eicosanoid Networks in Aspirin Exacerbated Respiratory Disease
Role: Principal Investigator
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U19AI095219
(BOYCE, JOSHUA A)
Jul 15, 2011 - Apr 30, 2026
Pathophysiologic and Therapeutic Mechanisms of Aspirin Exacerbated Respiratory Disease
Role: Principal Investigator
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U01HL102225
(ISRAEL, ELLIOT)
Jun 1, 2010 - Nov 30, 2015
Kit Inhibition in Asthma (KIA)
Role: Principal Investigator
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R21AI082369
(BOYCE, JOSHUA A)
Aug 1, 2009 - Jul 31, 2011
Lipidomic and Transcriptome Signatures in Aspirin-Exacerbated Respiratory Disease
Role: Principal Investigator
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R01AI078908
(BOYCE, JOSHUA A)
Apr 1, 2008 - Jul 31, 2026
Control of Pulmonary Inflammation by Leukotriene E4
Role: Principal Investigator
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R37AI052353
(BOYCE, JOSHUA A)
Aug 1, 2002 - Dec 31, 2022
CysLT and P2Y Receptors in Lung Inflammation
Role: Principal Investigator
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R01AI052353
(BOYCE, JOSHUA A)
Aug 1, 2002 - Dec 31, 2012
CysLT and P2Y Receptors in Lung Inflammation
Role: Principal Investigator
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R56AI052353
(BOYCE, JOSHUA A)
Aug 1, 2002 - Jan 14, 2008
CysLt and P2Y Receptors and Lung Inflammation
Role: Principal Investigator
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R01AI048802
(BOYCE, JOSHUA A)
May 1, 2002 - Apr 30, 2008
The Role of Mast Cells in Lung Inflammation
Role: Principal Investigator
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K11AI001304
(BOYCE, JOSHUA A)
Apr 1, 1996 - Mar 31, 2001
FUNCTION OF IMMATURE HYPODENSE HUMAN EOSINOPHILS
Role: Principal Investigator
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P01AI031599
(AUSTEN, KARL FRANK)
Sep 1, 1991 - Feb 29, 2008
Cellular Basis of Hypersensitivity Diseases in Humans
Role: Co-Principal Investigator
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P01HL036110
(BOYCE, JOSHUA A)
Sep 1, 1985 - May 31, 2011
Chemical Mediators of Acute Pulmonary Disorders
Role: Principal Investigator
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T32AI007306
(BOYCE, JOSHUA A)
Jul 1, 1985 - Jul 31, 2024
Immunologic Basis of Resistance and Hypersensitivity
Role: Principal Investigator
Bibliographic
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