课题基金 / 基金详情

Project 2: Identifying Metabolic vulnerabilities and targets in cancers with mutations in hamartoma genes

Project 2: Identifying Metabolic vulnerabilities and targets in cancers with mutations in hamartoma genes
项目 2:识别错构瘤基因突变癌症的代谢脆弱性和靶点
批准号:
10715600
负责人:
DAVID J. KWIATKOWSKI
金额:
$59.15万
依托单位国家:
美国
项目类别:
财政年份:
2007
资助国家:
美国
项目状态:
未结题
起止时间:
2007-04-24 至 2028-07-31

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中文摘要
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项目二:摘要
英文摘要
Project 2: Abstract The hypothesis guiding this proposal is that mutations in hamartoma syndrome genes (PTEN, LKB1, TSC1, TSC2) dominantly rewire metabolism exposing unique vulnerabilities. The focus of this project is to better understand the molecular and biochemical basis for the metabolic vulnerabilities and provide preclinical data that would support the development of biomarker driven clinical trials to evaluate such drugs in patients with germline or the many tumors containing sporadic mutations in hamartoma syndrome genes. We have decoded the optimal substrate motif for every single mammalian protein kinase in the last funding period and made an algorithm that allows us to decode which kinases are active or inactive in a given biological samples based on unbiased phospho-proteomics. Here we will focus on use of this new method to identify new metabolic enzymes targeted by LKB1-dependent kinases. The specific aims are: 1) Defining critical kinase- substrate interactions deregulated in hamartoma genes in cell lines and tissues; 2) Defining metabolic vulnerabilities deregulated in hamartoma genes in cell lines and tissues; and 3) Defining how AMPK control of TFEB contributes to the survival of hamartoma cells and how to target tumors based on new understanding of this pathway.
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Integrative molecular dissection of acquired resistance to PD1/PD-L1 blockade in localized and metastatic urothelial carcinoma
  • 批准号:
    10218294
  • 项目类别:
  • 资助金额:
    $47.63万
  • 财政年份:
    2021
  • 负责人:
    DAVID J. KWIATKOWSKI
  • 依托单位:
Genetics of LAM
  • 批准号:
    10318188
  • 项目类别:
  • 资助金额:
    $44.97万
  • 财政年份:
    2020
  • 负责人:
    DAVID J. KWIATKOWSKI
  • 依托单位:
Genetics of LAM
  • 批准号:
    10524041
  • 项目类别:
  • 资助金额:
    $44.97万
  • 财政年份:
    2020
  • 负责人:
    DAVID J. KWIATKOWSKI
  • 依托单位:
Molecular Pathogenesis of the Hamartoma Syndromes
  • 批准号:
    8719031
  • 项目类别:
  • 资助金额:
    $172.72万
  • 财政年份:
    2007
  • 负责人:
    DAVID J. KWIATKOWSKI
  • 依托单位:
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