Abnormal STAT3 Signaling and Aberrant O-Glycosylation of IgA1 in IgA Nephropathy
IgA 肾病中 STAT3 信号异常和 IgA1 异常 O-糖基化
基本信息
- 批准号:10384158
- 负责人:
- 金额:$ 15.27万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-08-01 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:Administrative SupplementAntigen-Antibody ComplexAntigensAutoantigensAutoimmune DiseasesAwardB-LymphocytesCOVID-19CellsCollaborationsDataDepositionDialysis procedureEnzymesFutureGoalsGrantIGA GlomerulonephritisIgA1ImmuneImmune systemIndividualKidneyLearningManuscriptsMentorsMolecular BiologyNational Institute of Diabetes and Digestive and Kidney DiseasesPatientsProductionRenal functionResearchResearch PersonnelResearch TrainingSignal TransductionStat3 proteinTimeTrainingTraining ProgramsTransplantationUniversitiesWritingbasecytokinedrug developmentexperienceexperimental studyglycosylationprofessorprogramsrenal damageskills
项目摘要
Project Summary/Abstract
The purpose of this proposal for the K01 Administrative Supplemental Award from the NIDDK is to enhance
the learning and research skills of the applicant in order to transition into an independent investigator. The
justification portion of this proposal outlines the critical timeframes that the COVID-19 restrictions occurred
under, and how this led to ceased production when manuscripts and grant preliminary data was being
generated. The research portion of this proposal is focused on the mechanisms of autoantigen production in
IgA nephropathy (IgAN), and how the applicant will finish critical experiments necessary for a successful R01-
A1 submission.
The goal of the applicant is to become an independent investigator, and as a current assistant
professor this will require more training and time. This will be accomplished through collaboration with mentors
who have extensive experience in molecular biology research, and execution of experiments listed in the
research strategy. The university has exceptional core programs set up to help young investigators with finding
and writing grants, obtaining proper collaborative expertise, research training programs, and lab management
courses.
IgAN is an autoimmune disease, which leads to decreased kidney function, with 40-50% of patients
requiring dialysis and/or transplantation. In this autoimmune disease, B cells from the immune system produce
IgA1 that has an aberrant glycosylation (termed Gd-IgA1) that causes the body to recognize IgA1 as a foreign
antigen. The autoantigen, Gd-IgA1, is elevated in IgAN patients and forms the basis for immune-complex
formation, which deposits in the kidney, leading to progressive kidney damage. The aims of this proposal are
to identify mechanisms responsible for elevated Gd-IgA1 production in patient B cells after cytokine exposure.
Identification of specific glycosylation enzymes that are differentially regulated and over activation signal
transducer and activator of transcription 3 (STAT3) by cytokines in IgAN patient B cells has provided us with a
strong starting point. We propose to investigate mechanisms responsible for altered signaling in IgAN patients,
thereby providing a bases for future drug development to reduce autoantigen production.
项目总结/摘要
NIDDK的K 01行政补充裁决提案的目的是提高
申请人的学习和研究技能,以便转变为独立调查员。的
该提案的理由部分概述了COVID-19限制措施实施的关键时间框架
下,以及如何这导致停止生产时,手稿和赠款初步数据正在
生成的.该提案的研究部分集中在自身抗原产生的机制,
伊加肾病(IgAN),以及申请人将如何完成成功R 01所需的关键实验-
A1提交。
申请人的目标是成为一名独立的调查员,并作为目前的助理
教授,这需要更多的训练和时间。这将通过与导师的合作来实现
他们在分子生物学研究方面拥有丰富的经验,并执行了
研究策略。该大学有特殊的核心计划,以帮助年轻的调查人员发现
撰写赠款,获得适当的合作专业知识,研究培训计划和实验室管理
课程
IgAN是一种自身免疫性疾病,导致肾功能下降,40-50%的患者
需要透析和/或移植。在这种自身免疫性疾病中,来自免疫系统的B细胞产生
具有异常糖基化的IgA 1(称为Gd-IgA 1),导致机体将IgA 1识别为外源性IgA。
抗原的自身抗原Gd-IgA 1在IgAN患者中升高,并形成免疫复合物的基础
形成,其沉积在肾脏中,导致进行性肾损伤。这项建议的目的是
确定细胞因子暴露后患者B细胞中Gd-IgA 1产生升高的机制。
鉴定差异调节和过度激活信号的特异性糖基化酶
在IgAN患者B细胞中,细胞因子对转录转导子和转录激活子3(STAT 3)的影响为我们提供了一个
强有力的起点。我们建议调查负责IgAN患者信号改变的机制,
从而为将来开发减少自身抗原产生的药物提供了基础。
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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Colin Robert Reily其他文献
Mitochondrial Targeted Antioxidant MitoQ Modulates Smad2/3 and β-catenin Signaling Pathways in the Prevention of Diabetes Induced Kidney Damage
- DOI:
10.1016/j.freeradbiomed.2010.10.083 - 发表时间:
2010-01-01 - 期刊:
- 影响因子:
- 作者:
Colin Robert Reily - 通讯作者:
Colin Robert Reily
Colin Robert Reily的其他文献
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{{ truncateString('Colin Robert Reily', 18)}}的其他基金
Distinct Glycophenotypes with Abnormal Signaling Define a Subpopulation of B cells Responsible for Production of Galactose-Deficient IgA1, the Main Autoantigen in IgA Nephropathy
具有异常信号传导的独特糖表型定义了负责产生半乳糖缺陷型 IgA1(IgA 肾病的主要自身抗原)的 B 细胞亚群
- 批准号:
10563618 - 财政年份:2023
- 资助金额:
$ 15.27万 - 项目类别:
Abnormal cytokine response and autoantigen production in IgA-producing subpopulations in IgA nephropathy
IgA 肾病中 IgA 产生亚群的异常细胞因子反应和自身抗原产生
- 批准号:
9807239 - 财政年份:2019
- 资助金额:
$ 15.27万 - 项目类别:
Abnormal STAT3 signaling and aberrant O-glycosylation of IgA1 in IgA nephropathy
IgA 肾病中 STAT3 信号异常和 IgA1 异常 O-糖基化
- 批准号:
8949844 - 财政年份:2015
- 资助金额:
$ 15.27万 - 项目类别:
Abnormal STAT3 signaling and aberrant O-glycosylation of IgA1 in IgA nephropathy
IgA 肾病中 STAT3 信号异常和 IgA1 异常 O-糖基化
- 批准号:
9750059 - 财政年份:2015
- 资助金额:
$ 15.27万 - 项目类别:
Abnormal STAT3 signaling and aberrant O-glycosylation of IgA1 in IgA nephropathy
IgA 肾病中 STAT3 信号异常和 IgA1 异常 O-糖基化
- 批准号:
9341290 - 财政年份:2015
- 资助金额:
$ 15.27万 - 项目类别:
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