Germline mutations of PTPN11 (SHP-2) in the stem cell microenvironment

干细胞微环境中 PTPN11 (SHP-2) 的种系突变

基本信息

  • 批准号:
    9327048
  • 负责人:
  • 金额:
    $ 39万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-08-05 至 2020-06-30
  • 项目状态:
    已结题

项目摘要

Project Summary Patients with Noonan syndrome (NS), a developmental disorder characterized by congenital heart disease, dysmorphic facial structures, short stature, and mental retardation, are at an increased risk of developing leukemias, especially juvenile myelomonocytic leukemia (JMML), a fatal childhood myeloproliferative neoplasm (MPN). The mechanisms underlying the leukemogenesis are not completely understood. Lack of such knowledge impedes the development of therapeutic interventions for effectively controlling leukemic progression in NS and for improving treatment outcomes in NS-associated leukemias. Germline activating mutations of PTPN11 (encoding SHP2), a protein tyrosine phosphatase that we previously demonstrated is required for embryogenesis and hematopoietic cell development, are associated with more than 50% of patients with NS. Studies from our laboratory and others have established a cell-intrinsic role of PTPN11 mutations in NS and associated leukemias. Intriguingly, our most recent studies suggest that PTPN11 mutations in the bone marrow (BM) microenvironment can also induce a profound myeloid malignancy. The objective of the current project is to determine the cellular and molecular mechanisms by which PTPN11 mutated microenvironmental cells impact resident hematopoietic stem cells. The central hypothesis of the proposal is that germline PTPN11 mutations in the BM microenvironment greatly promote the leukemic progression in NS and cause stem cell transplantation failure. We plan to test this hypothesis and accomplish the objective of this application by pursuing the following aims. 1). Identify the cellular components and protein factors that mediate the leukemogenic effects of PTPN11 mutations in the BM microenvironment. 2). Determine the molecular mechanisms by which PTPN11 mutations change the activities of microenvironmental cells. 3). validate the pathogenic effects of PTPN11 mutations in NS patient-derived BM microenvironmental cells. This project will not only greatly advance our understanding of the pathogenesis of NS-associated leukemias, but also provide a molecular basis for the rational design of new therapeutics targeting the detrimental microenvironment in NS patients, which may eventually lead to significant improvements in controlling leukemic progression in NS and in stem cell transplantation therapy for NS-associated leukemias.
项目总结

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)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

CHENG-KUI QU其他文献

CHENG-KUI QU的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('CHENG-KUI QU', 18)}}的其他基金

Targeting leukemic stem cells in acute myeloid leukemia
靶向治疗急性髓系白血病的白血病干细胞
  • 批准号:
    10561291
  • 财政年份:
    2023
  • 资助金额:
    $ 39万
  • 项目类别:
Eradicating leukemic stem cells in juvenile myelomonocytic leukemia
根除幼年粒单核细胞白血病中的白血病干细胞
  • 批准号:
    10722045
  • 财政年份:
    2023
  • 资助金额:
    $ 39万
  • 项目类别:
Metabolic regulation of stem cell niche development and function
干细胞生态位发育和功能的代谢调节
  • 批准号:
    10581643
  • 财政年份:
    2022
  • 资助金额:
    $ 39万
  • 项目类别:
Metabolic regulation of stem cell niche development and function
干细胞生态位发育和功能的代谢调节
  • 批准号:
    10416234
  • 财政年份:
    2022
  • 资助金额:
    $ 39万
  • 项目类别:
Synthetic lethality in leukemic stem cells in juvenile myelomonocytic leukemia
幼年型粒单核细胞白血病干细胞的综合致死率
  • 批准号:
    10308711
  • 财政年份:
    2020
  • 资助金额:
    $ 39万
  • 项目类别:
Germline mutations of PTPN11 (SHP2) in the stem cell microenvironment
干细胞微环境中 PTPN11 (SHP2) 的种系突变
  • 批准号:
    10208202
  • 财政年份:
    2016
  • 资助金额:
    $ 39万
  • 项目类别:
Germline mutations of PTPN11 (SHP2) in the stem cell microenvironment
干细胞微环境中 PTPN11 (SHP2) 的种系突变
  • 批准号:
    10369684
  • 财政年份:
    2016
  • 资助金额:
    $ 39万
  • 项目类别:
Germline mutations of PTPN11 (SHP-2) in the stem cell microenvironment
干细胞微环境中 PTPN11 (SHP-2) 的种系突变
  • 批准号:
    9174534
  • 财政年份:
    2016
  • 资助金额:
    $ 39万
  • 项目类别:
Germline mutations of PTPN11 (SHP2) in the stem cell microenvironment
干细胞微环境中 PTPN11 (SHP2) 的种系突变
  • 批准号:
    10642661
  • 财政年份:
    2016
  • 资助金额:
    $ 39万
  • 项目类别:
Targeting metabolism in leukemic stem cells
靶向白血病干细胞的代谢
  • 批准号:
    8619417
  • 财政年份:
    2014
  • 资助金额:
    $ 39万
  • 项目类别:

相似海外基金

Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
  • 批准号:
    MR/S03398X/2
  • 财政年份:
    2024
  • 资助金额:
    $ 39万
  • 项目类别:
    Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
  • 批准号:
    EP/Y001486/1
  • 财政年份:
    2024
  • 资助金额:
    $ 39万
  • 项目类别:
    Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
  • 批准号:
    2338423
  • 财政年份:
    2024
  • 资助金额:
    $ 39万
  • 项目类别:
    Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
  • 批准号:
    MR/X03657X/1
  • 财政年份:
    2024
  • 资助金额:
    $ 39万
  • 项目类别:
    Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
  • 批准号:
    2348066
  • 财政年份:
    2024
  • 资助金额:
    $ 39万
  • 项目类别:
    Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
  • 批准号:
    2341402
  • 财政年份:
    2024
  • 资助金额:
    $ 39万
  • 项目类别:
    Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
  • 批准号:
    AH/Z505481/1
  • 财政年份:
    2024
  • 资助金额:
    $ 39万
  • 项目类别:
    Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10107647
  • 财政年份:
    2024
  • 资助金额:
    $ 39万
  • 项目类别:
    EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
  • 批准号:
    10106221
  • 财政年份:
    2024
  • 资助金额:
    $ 39万
  • 项目类别:
    EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
  • 批准号:
    AH/Z505341/1
  • 财政年份:
    2024
  • 资助金额:
    $ 39万
  • 项目类别:
    Research Grant
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了