Using BTK Inhibitors to Prevent Anaphylactic Drug Reactions
使用 BTK 抑制剂预防过敏性药物反应
基本信息
- 批准号:9890681
- 负责人:
- 金额:$ 19.56万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-02-22 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:Agammaglobulinaemia tyrosine kinaseAllergen ImmunotherapyAllergensAllergicAllergic ReactionAnaphylaxisAwardB-LymphocytesBasophilsBiological MarkersBiometryCCL2 geneCD34 geneCellsCellular biologyClinicalClinical ImmunologyClinical TrialsCutaneousDataDevelopmentDoctor of PhilosophyDoseEpinephrineExposure toFDA approvedFoodFrequenciesFundingGoalsGrantHistamineHumanHypersensitivityHypersensitivity skin testingIL8 geneIgEImmune responseImmunologistImmunologyImmunotherapyIn VitroInflammatoryInpatientsInsect StingInterleukin-6KineticsLearningLeukocytesLeukotriene C4LifeLogicMeasurementMediatingMediator of activation proteinMedicineMentorsMusNutsOralPathway interactionsPatient CarePatientsPenicillin AllergyPenicillinsPeripheralPharmaceutical PreparationsPharmacologyPhasePhenotypePhosphotransferasesPlasmaPreventive therapyPrincipal InvestigatorProductionProstaglandin D2ReactionReceptor SignalingReceptors, Antigen, B-CellResearchResearch DesignResearch PersonnelRiskRoleSamplingScientistSerumSeveritiesSignal PathwaySignal TransductionSkinSmall Interfering RNASpecificityStimulusStudy SkillsTNF geneTestingTissuesTrainingTranslational ResearchTreesTryptaseTyrosine Kinase InhibitorUniversitiesVenomsWorkX-Linked Agammaglobulinemiabeta-n-acetylhexosaminidasecare outcomescareercell typeclinical carecostcost effectivecytokinedesensitizationdesignexperimental studyfood challengehuman modelhuman tissuehumanized mouseimprovedin vivoin vivo Modelinhibitor/antagonistmast cellmedical schoolsmouse modelnovelnovel strategiesnovel therapeuticsopen labelpatient orientedpreventprofessorskillsskin prick teststandard of carestem cellstranslational physician
项目摘要
PROJECT SUMMARY/ABSTRACT
This proposal describes a 5-year training award to develop the academic career of the principal
investigator, Melanie C. Dispenza, MD, PhD, a board-certified allergist-immunologist at the Northwestern
University Feinberg School of Medicine. Her qualifications and background, combined with her current research
in preventing IgE-mediated activation of mast cells and basophils, make her uniquely qualified to study novel
therapies to prevent anaphylaxis. During the period of this proposal, Dr. Dispenza will continue to devote at least
75% effort towards patient-oriented translational research.
Anaphylaxis is a potentially life-threatening IgE-mediated systemic allergic reaction with no known
preventative therapies. There is a huge unmet need for therapies that can reduce the frequency and/or severity
of anaphylactic reactions from both accidental and intentional exposures, the latter including desensitizations
and immunotherapy. Bruton’s tyrosine kinase (BTK) is a key component of FcεRI signaling in human mast cells
and basophils. Pharmacologic inhibitors of BTK are generally well tolerated, and preliminary data show that BTK
inhibitors effectively block IgE-mediated human mast cell and basophil activation in vitro and in mouse models
of anaphylaxis in vivo. Thus, it may be possible to utilize BTK inhibitors to proactively prevent allergic reactions
including anaphylaxis. The overarching hypothesis of this proposal is that short-term use of FDA-approved BTK
inhibitors such as ibrutinib will prevent medication-induced anaphylaxis in both mouse models of anaphylaxis
and in humans. If successful, BTK inhibitors could potentially be used to make drug desensitization safer and
more cost effective, thus improving patient care and outcomes.
Through this proposed research, Dr. Dispenza will work towards her long-term goal of becoming an
independent translational physician-scientist. Short-term goals include (1) expanding research skills in mast cell
biology, (2) learning to implement novel humanized mouse models of anaphylaxis, and (3) acquiring biostatistical
and clinical trial skills for study design and implementation. After completion of this award, Dr. Dispenza will
have had the needed training to design and implement further studies on the development of novel strategies to
prevent anaphylaxis. To achieve these goals, an excellent mentoring team has been assembled. The primary
mentor, Bruce Bochner, MD (Professor, Division of Allergy-Immunology, Department of Medicine), has a strong
track record of translational research in allergy including mast cell biology and has successfully trained many
academicians. Donald MacGlashan, Jr, MD, PhD (Director, Division of Allergy and Clinical Immunology, Johns
Hopkins University), will serve as co-mentor, with additional expertise in mast cell and basophil activation and
signaling. The mentoring team will oversee Dr. Dispenza’s progress in developing the necessary skills in order
to support her transition into an independent investigator.
项目总结/文摘
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Melanie C. Dispenza其他文献
Research Advances in Mast Cell Biology and Their Translation Into Novel Therapies for Anaphylaxis
肥大细胞生物学研究进展及其在过敏反应新疗法中的转化
- DOI:
10.1016/j.jaip.2023.03.015 - 发表时间:
2023-07-01 - 期刊:
- 影响因子:6.600
- 作者:
Melanie C. Dispenza;Dean D. Metcalfe;Ana Olivera - 通讯作者:
Ana Olivera
Melanie C. Dispenza的其他文献
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{{ truncateString('Melanie C. Dispenza', 18)}}的其他基金
Using BTK Inhibitors to Prevent Anaphylactic Drug Reactions
使用 BTK 抑制剂预防过敏性药物反应
- 批准号:
10112819 - 财政年份:2020
- 资助金额:
$ 19.56万 - 项目类别:
Using BTK Inhibitors to Prevent Anaphylactic Drug Reactions
使用 BTK 抑制剂预防过敏性药物反应
- 批准号:
10329987 - 财政年份:2020
- 资助金额:
$ 19.56万 - 项目类别:
Using BTK Inhibitors to Prevent Anaphylactic Drug Reactions
使用 BTK 抑制剂预防过敏性药物反应
- 批准号:
10844835 - 财政年份:2020
- 资助金额:
$ 19.56万 - 项目类别:
Using BTK Inhibitors to Prevent Anaphylactic Drug Reactions
使用 BTK 抑制剂预防过敏性药物反应
- 批准号:
10551351 - 财政年份:2020
- 资助金额:
$ 19.56万 - 项目类别:
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