Myeloablative conditioning and late complications in ARTEMIS-deficient SCID

ARTEMIS 缺陷 SCID 的清髓调理和晚期并发症

基本信息

  • 批准号:
    9251366
  • 负责人:
  • 金额:
    $ 23.25万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-07-20 至 2019-06-30
  • 项目状态:
    已结题

项目摘要

PROJECT ABSTRACT The vastly diverse antigen receptor genes are assembled from numerous V, D and J coding segments via the lymphoid specific DNA rearrangement, V(D)J recombination. Defective V(D)J recombination impairs lymphocyte development and thus, results in immunodeficiency. The non-homologous end joining (NHEJ) pathway is required during V(D)J recombination by virtue of its role as one of the major DNA double strand break (DSB) repair pathways. Mutations in nearly all of the NHEJ genes have been found in association with human primary immunodeficiency syndromes. ARTEMIS is the most frequently mutated NHEJ gene and was initially discovered in the radiation sensitive severe combined immunodeficiency syndrome, RS-SCID. NHEJ- deficient patients can undergo hematopoietic cell transplantation to reconstitute T and B cell functions. However, because NHEJ is critical for DSB repair in all cell types, conditioning regimens involving radiation cause excessive tissue damage and can lead to mortality. ARTEMIS-deficient patients have been successfully engrafted with T and B cells with myeloablative conditioning using alkylating agents. However, these patients exhibit late complications including growth failure, endocrine deficiencies and dental abnormalities. The goals of this proposal are to elucidate the mechanisms underlying the toxicities associated with myeloablative conditioning with alkylating agents using our previously developed and characterized mouse models of NHEJ- deficient SCID and to determine the efficacy of alternative conditioning regimens. The potential for late onset tumorigenesis associated will also be examined. Together, these studies will provide mechanistic insight into the causes of late toxicities in NHEJ-deficient primary immunodeficiencies and potentially lead to the development of more effective therapies.
项目摘要

项目成果

期刊论文数量(0)
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会议论文数量(0)
专利数量(0)

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JoAnn Sekiguchi其他文献

JoAnn Sekiguchi的其他文献

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{{ truncateString('JoAnn Sekiguchi', 18)}}的其他基金

Molecular mechanisms of lung disease in ataxia telangiectasia
共济失调性毛细血管扩张性肺部疾病的分子机制
  • 批准号:
    8582506
  • 财政年份:
    2010
  • 资助金额:
    $ 23.25万
  • 项目类别:
Molecular mechanisms of lung disease in ataxia telangiectasia
共济失调性毛细血管扩张性肺部疾病的分子机制
  • 批准号:
    8204498
  • 财政年份:
    2010
  • 资助金额:
    $ 23.25万
  • 项目类别:
Roles of the Artemis nuclease in DNA repair and disease
Artemis 核酸酶在 DNA 修复和疾病中的作用
  • 批准号:
    8072925
  • 财政年份:
    2010
  • 资助金额:
    $ 23.25万
  • 项目类别:
Molecular mechanisms of lung disease in ataxia telangiectasia
共济失调性毛细血管扩张性肺部疾病的分子机制
  • 批准号:
    8040274
  • 财政年份:
    2010
  • 资助金额:
    $ 23.25万
  • 项目类别:
Molecular mechanisms of lung disease in ataxia telangiectasia
共济失调性毛细血管扩张性肺部疾病的分子机制
  • 批准号:
    8386672
  • 财政年份:
    2010
  • 资助金额:
    $ 23.25万
  • 项目类别:
Mechanism and regulation of DNA end processing in V(D)J recombination and repair
V(D)J重组和修复中DNA末端加工的机制和调控
  • 批准号:
    8116793
  • 财政年份:
    2010
  • 资助金额:
    $ 23.25万
  • 项目类别:
Roles of the Artemis nuclease in DNA repair and disease
Artemis 核酸酶在 DNA 修复和疾病中的作用
  • 批准号:
    6993660
  • 财政年份:
    2005
  • 资助金额:
    $ 23.25万
  • 项目类别:
Mechanism and regulation of DNA end processing in V(D)J recombination and repair
V(D)J重组和修复中DNA末端加工的机制和调控
  • 批准号:
    8097247
  • 财政年份:
    2005
  • 资助金额:
    $ 23.25万
  • 项目类别:
Mechanism and regulation of DNA end processing in V(D)J recombination and repair
V(D)J重组和修复中DNA末端加工的机制和调控
  • 批准号:
    8488394
  • 财政年份:
    2005
  • 资助金额:
    $ 23.25万
  • 项目类别:
Roles of the Artemis nuclease in DNA repair and disease
Artemis 核酸酶在 DNA 修复和疾病中的作用
  • 批准号:
    7555918
  • 财政年份:
    2005
  • 资助金额:
    $ 23.25万
  • 项目类别:

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