High Throughput Method to Assess SNP Functionality in Prostate Cancer

高通量方法评估前列腺癌中的 SNP 功能

基本信息

  • 批准号:
    8336846
  • 负责人:
  • 金额:
    $ 14.47万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-09-21 至 2014-08-31
  • 项目状态:
    已结题

项目摘要

Project Summary High Throughput Method to Assess SNP Functionality in Prostate Cancer PIs: Christopher L. Warren and Mary S. Ozers A critical unmet need in implementing personalized medicine is the ability to sort through the millions of single nucleotide polymorphisms (SNPs) present in the human genome and to pinpoint which of these DNA variations are causative in disease. A key under-studied function of SNPs is their ability to generate or disrupt genomic binding sites for transcription factors involved in cancer. Toward this goal, we are inventing the SNP-SNAP (Specificity and Affinity for Proteins) microarray as a prototype high throughput device to evaluate SNP function. The SNP-SNAP arrays will be used to display a quarter-million prostate cancer- related SNPs as double-stranded DNA molecules and to assay transcription factors (i.e. drug targets) for their binding to these SNP DNA sequences. The resulting data will be correlated with prostate cancer incidence. The million-plus data points from the SNP-SNAP arrays will be analyzed using SNP-Sequence Specificity Landscapes, creating a prostate cancer "molecular signature" that relates transcription factor binding, SNP preferences, and chromosomal position of the nearest genes. Our findings will also relate prostate cancer-associated SNP function with cancer stage and aggressiveness. Understanding SNP function will have a major impact on personalized medicine, by providing individualized disease risk assessment, identifying new personalized therapeutic targets, and predicting efficacy and potential off- target side effects of common therapeutics. The goals of this Phase I project are to: 1. Design and synthesize a customized SNP-SNAP DNA microarray to tile across a quarter-million SNPs that are associated with prostate cancer. 2. Examine the DNA binding specificity and affinity of 5 prostate cancer-related transcription factors, as purified proteins and from cell lysates, on the SNP-SNAP array and annotate the human genome with the transcription factor binding differences due to SNPs. Verify results with chromatin immunoprecipitation in prostate cancer cells. 3. Obtain SNP data from patients with prostate cancer and determine if there is a statistically significant association of functional SNPs, which yielded differential binding of prostate cancer specific transcription factors on the SNP-SNAP array, with prostate cancer incidence. This technology can assay millions of SNPs and multiple transcription factors simultaneously, thus representing one of the first methods to evaluate SNP functionality in a high throughput manner. Our SNP- SNAP technology, by virtue of the array custom design and ability to examine millions of DNA permutations, is also broadly applicable to any cancer type and disease model.
项目总结

项目成果

期刊论文数量(0)
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Mary Szatkowski Ozers其他文献

Mary Szatkowski Ozers的其他文献

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{{ truncateString('Mary Szatkowski Ozers', 18)}}的其他基金

Development of GenomeBuild as a Universal Method to Synthesize Genomes
GenomeBuild 的开发作为合成基因组的通用方法
  • 批准号:
    10565058
  • 财政年份:
    2023
  • 资助金额:
    $ 14.47万
  • 项目类别:
SNAP-X: Development of a Mutagenesis Strategy and High Density Protein Array to Comprehensively Display Protein Variants
SNAP-X:开发诱变策略和高密度蛋白质阵列以全面展示蛋白质变体
  • 批准号:
    9923621
  • 财政年份:
    2019
  • 资助金额:
    $ 14.47万
  • 项目类别:
SNAP-X: Development of a Mutagenesis Strategy and High Density Protein Array to Comprehensively Display Protein Variants
SNAP-X:开发诱变策略和高密度蛋白质阵列以全面展示蛋白质变体
  • 批准号:
    10203604
  • 财政年份:
    2019
  • 资助金额:
    $ 14.47万
  • 项目类别:
Aptamer-Based Detection of Cardiac Biomarker Glycosylation States Using APT-SNAP
使用 APT-SNAP 基于适体的心脏生物标志物糖基化状态检测
  • 批准号:
    8648358
  • 财政年份:
    2014
  • 资助金额:
    $ 14.47万
  • 项目类别:
Aptamer-Based Detection of Cardiac Biomarker Glycosylation States Using APT-SNAP
使用 APT-SNAP 基于适体的心脏生物标志物糖基化状态检测
  • 批准号:
    8914454
  • 财政年份:
    2014
  • 资助金额:
    $ 14.47万
  • 项目类别:
High Density Peptide Arrays for Cancer-Related Post-Translational Modifications
用于癌症相关翻译后修饰的高密度肽阵列
  • 批准号:
    8738628
  • 财政年份:
    2013
  • 资助金额:
    $ 14.47万
  • 项目类别:
High Density Peptide Arrays for Cancer-Related Post-Translational Modifications
用于癌症相关翻译后修饰的高密度肽阵列
  • 批准号:
    8625055
  • 财政年份:
    2013
  • 资助金额:
    $ 14.47万
  • 项目类别:
High Throughput Method to Assess SNP Functionality in Prostate Cancer
高通量方法评估前列腺癌中的 SNP 功能
  • 批准号:
    8222682
  • 财政年份:
    2011
  • 资助金额:
    $ 14.47万
  • 项目类别:
Screening of FoxA1-ER-DNA disruptors for development of breast cancer therapeutic
筛选 FoxA1-ER-DNA 干扰物用于开发乳腺癌治疗药物
  • 批准号:
    8200699
  • 财政年份:
    2011
  • 资助金额:
    $ 14.47万
  • 项目类别:
Screening of glucocorticoid receptor small-molecule regulators using cognate site
使用同源位点筛选糖皮质激素受体小分子调节剂
  • 批准号:
    7671718
  • 财政年份:
    2009
  • 资助金额:
    $ 14.47万
  • 项目类别:

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