Mouse Asthma
Mouse Asthma
批准号:
7476207
负责人:
DANIEL H CONRAD
金额:
$18.59万
依托单位国家:
美国
项目类别:
财政年份:
2008
资助国家:
美国
项目状态:
已结题
起止时间:
2008-04-01 至 2013-03-31
关键词:
AerosolsAffectAllergensAllergicAnimalsAsthmaBreathingCellsChemicalsCollaborationsCollectionConditionCore FacilityData AnalysesDevelopmentDiseaseDisease modelEffectivenessEvaluationFunctional disorderGenetic VariationHistologyHumanHypersensitivityIDEC-152 Monoclonal AntibodyIgEInfiltrationInflammationIntranasal AdministrationLaboratoriesLeadLifeLipidsLiquid substanceLungMaintenanceMeasurementMediatingMembraneMethodologyMethodsModalityModelingMonitorMusOperative Surgical ProceduresOrganOvalbuminPathologyPhenotypePhosphotransferasesPreparationProductionProtein OverexpressionRNA analysisRelative (related person)RoleRouteSPHK1 enzymeSmall Interfering RNASphingosineSymptomsSystemTestingTherapeutic InterventionToxic effectTransgenic Organismsaerosolizedchemokineconceptcytokinedayeosinophilin vivoinhibitor/antagonistknock-downknockout animalmast cellmouse modelnovelprogramsprotective effectresearch studyresponsesphingosine kinasesrc-Family Kinasestranscription factor
中文摘要
小鼠哮喘模型核心(Science Core C)将协调和执行项目中的实验
2、3和4,涉及小鼠哮喘模型。在项目4中,领导者斯皮格尔博士已经开发出
神经鞘氨醇-1-激酶的特异性抑制剂,并将在吸入模型中使用这些药物直接使它们
肺部。这在很大程度上避免了全身毒性,并直接针对受影响的器官。这个概念是
测试的是抑制肺肥大细胞是否足以抑制哮喘模型。此外,
项目主任将使用siRNA在体内阻断肺内鞘氨醇激酶的合成,以便
确定这是否会抑制哮喘的发展。在项目2中,康拉德博士已经证明了
CD23的过度表达抑制了IgE的产生和嗜酸性粒细胞向肺的募集。实验将会
以确定IgE是否为嗜酸性粒细胞募集所必需。此外,CD23
Sheddase已被鉴定为Adam 10,siRNA敲除实验将在
与Spiegel博士合作确定是否通过siRNA或特定的基因在肺中阻断ADAM10
抑制剂会影响哮喘的发展和症状。在项目3中,瑞安博士正在检查
LYN基因敲除动物的过敏表型,目的是测定LYN在
肥大细胞。LYN“‘”小鼠已知会患上严重的Th2疾病,包括IgE升高和
嗜酸性粒细胞反应。毫不奇怪,这些活动会导致严重的哮喘表型。在……里面
与康拉德博士合作,LYN“‘”动物将与CD23转基因杂交,看看Th2是否
疾病是被调节的。此外,ADAM10抑制剂的活性可以通过siRNA或化学物质来实现
直接引入肺部的抑制剂方法学将测试其调节LYN的能力。
严重的Th2疾病模式。在所有这些研究中,核心将提供专业知识来执行
并分析小鼠哮喘模型的数据。这些措施包括对小鼠进行30天的维护
BAL液体收集和最终牺牲所需的敏化、气溶胶挑战和终极牺牲时间
肺组织学和RNA分析的准备。
英文摘要
The mouse asthma model core (scientific core C) will coordinate and perform the experiments in projects
2, 3 and 4 that involve the mouse asthma model. In Project 4, the Leader, Dr. Spiegel, has developed
specific inhibitors for sphingosine-1-kinase and will use these in an inhalent model to get them directly to
the lung. This largely avoids systemic toxicity and targets the affected organ directly. The concept being
tested is whether inhibition of lung mast cells is sufficient to inhibit the asthma model. In addition, the
program director will use siRNA to block, in vivo, in lung the synthesis of sphingosine kinase in order to
determine whether this will inhibit asthma development. In Project 2, Dr. Conrad has demonstrated that
overexperssion of CD23 inhibits IgE production and eosinophil recruitment to the lung. Experiments will
be performed to determine if IgE is necessary for the eosinophil recruitment. In addition, the CD23
sheddase has been identified as ADAM 10 and siRNA knock-down experiments will be performed in
collaboration with Dr. Spiegel to determine if blockade of ADAM10 in the lung, either by siRNA or specific
inhibitors influences asthma development and symptoms. In Project #3, Dr. Ryan is examining the
allergic phenotype of lyn knockout animals with the objective of determining the activities of lyn in the
mast cell. The lyn"'" mice are known to develop severe Th2 disease including increased IgE and
eosinophil responses. These activities, not surprisingly, lead to a severe asthma phenotype. In
collaboration with Dr, Conrad, the lyn"'" animals will be crossed to CD23 transgenics to see if the Th2
disease is modulated. In addition, the activities of ADAM10 inhibitors either via a siRNA or chemical
inhibitor methodology, introduced directly into the lung, will be tested for capacity to modulate the lyn"'"
severe Th2 disease modality. In all of these studies, the core will provide the expertise to both perform
and analyze data from the mouse asthma model. These include maintenance of mice for the 30 day
period required for sensitization, aerosol challenge and ultimate sacrifice with BAL fluid collection and
lung preparation for histology and RNA analysis.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
CD23 Destabilization and IgE Regulation
-
批准号:7476201
-
项目类别:
-
资助金额:$14.0万
-
财政年份:2008
-
负责人:DANIEL H CONRAD
-
依托单位:
BIACORE 3000 : IMMUNOLOGY, PROTEIN INTERACTIONS STUDIES,; LYME DISEASE
-
批准号:7166167
-
项目类别:
-
资助金额:$9.69万
-
财政年份:2005
-
负责人:DANIEL H CONRAD
-
依托单位:
Biacore 3000 shared instrument
-
批准号:6876818
-
项目类别:
-
资助金额:$29.07万
-
财政年份:2005
-
负责人:DANIEL H CONRAD
-
依托单位:
BIACORE 3000 : PROTEIN-NUCLEIC ACID INTERACTIONS, T CRUZI STUDIES
-
批准号:7166168
-
项目类别:
-
资助金额:$9.69万
-
财政年份:2005
-
负责人:DANIEL H CONRAD
-
依托单位:
BIACORE 3000 : PROTEIN DRUG INTERACTION STUDIES
-
批准号:7166169
-
项目类别:
-
资助金额:$9.69万
-
财政年份:2005
-
负责人:DANIEL H CONRAD
-
依托单位:
FACSCALIBER
-
批准号:6440238
-
项目类别:
-
资助金额:$11.45万
-
财政年份:2002
-
负责人:DANIEL H CONRAD
-
依托单位:
IGE CONTROL BY OVEREXPRESSION OF CD23
-
批准号:6170708
-
项目类别:
-
资助金额:$25.27万
-
财政年份:1999
-
负责人:DANIEL H CONRAD
-
依托单位:
IGE CONTROL BY OVEREXPRESSION OF CD23
-
批准号:2909174
-
项目类别:
-
资助金额:$25.11万
-
财政年份:1999
-
负责人:DANIEL H CONRAD
-
依托单位:
IGE CONTROL BY OVEREXPRESSION OF CD23
-
批准号:6632160
-
项目类别:
-
资助金额:$26.22万
-
财政年份:1999
-
负责人:DANIEL H CONRAD
-
依托单位:
IGE CONTROL BY OVEREXPRESSION OF CD23
-
批准号:6511121
-
项目类别:
-
资助金额:$25.45万
-
财政年份:1999
-
负责人:DANIEL H CONRAD
-
依托单位:
IGE CONTROL BY OVEREXPRESSION OF CD23
-
批准号:6374016
-
项目类别:
-
资助金额:$24.71万
-
财政年份:1999
-
负责人:DANIEL H CONRAD
-
依托单位:
Training in Hypersensitivity and Cancer Immunology
-
批准号:6499996
-
项目类别:
-
资助金额:$16.1万
-
财政年份:1992
-
负责人:DANIEL H CONRAD
-
依托单位:
TRAINING IN HYPERSENSITIVITY AND ANTIGEN PROCESSING
-
批准号:2058287
-
项目类别:
-
资助金额:$9.69万
-
财政年份:1992
-
负责人:DANIEL H CONRAD
-
依托单位:
TRAINING IN HYPERSENSITIVITY AND ANTIGEN PROCESSING
-
批准号:2058290
-
项目类别:
-
资助金额:$9.59万
-
财政年份:1992
-
负责人:DANIEL H CONRAD
-
依托单位:
TRAINING IN HYPERSENSITIVITY AND ANTIGEN PROCESSING
-
批准号:2671552
-
项目类别:
-
资助金额:$9.75万
-
财政年份:1992
-
负责人:DANIEL H CONRAD
-
依托单位:
TRAINING IN HYPERSENSITIVITY AND ANTIGEN PROCESSING
-
批准号:6372796
-
项目类别:
-
资助金额:$12.25万
-
财政年份:1992
-
负责人:DANIEL H CONRAD
-
依托单位:
Training in Hypersensitivity and Cancer Immunology
-
批准号:6940592
-
项目类别:
-
资助金额:$16.36万
-
财政年份:1992
-
负责人:DANIEL H CONRAD
-
依托单位:
TRAINING IN HYPERSENSITIVITY AND ANTIGEN PROCESSING
-
批准号:2330281
-
项目类别:
-
资助金额:$9.6万
-
财政年份:1992
-
负责人:DANIEL H CONRAD
-
依托单位:
Training in Hypersensitivity and Cancer Immunology
-
批准号:6652439
-
项目类别:
-
资助金额:$13.87万
-
财政年份:1992
-
负责人:DANIEL H CONRAD
-
依托单位:
TRAINING IN HYPERSENSITIVITY AND ANTIGEN PROCESSING
-
批准号:2058289
-
项目类别:
-
资助金额:$10.45万
-
财政年份:1992
-
负责人:DANIEL H CONRAD
-
依托单位:
海外基金