Research Initiation Award: Regulation of Gene Expression by the CD44-ICD Signaling Pathway

研究启动奖：CD44-ICD 信号通路对基因表达的调节

• 批准号: 1700228
• 负责人: Karl Miletti
• 金额: $ 30万
• 依托单位: Delaware State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-06-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1700228&HistoricalAwards=false
• 关键词: Research; Initiation; Award; Regulation; Gene

The Historically Black Colleges and Universities-Undergraduate Program (HBCU-UP) Research Initiation Awards (RIAs) provide support to STEM junior faculty at HBCUs who are starting to build a research program, as well as for mid-career faculty who may have returned to the faculty ranks after holding an administrative post or who need to redirect and rebuild a research program. Faculty members may pursue research at their home institution, at an NSF-funded Center, at a research intensive institution or at a national laboratory. The RIA projects are expected to help further the faculty member's research capability and effectiveness, to improve research and teaching at his or her home institution, and to involve undergraduate students in research experiences. With support from the National Science Foundation, Delaware State University (DSU) will conduct research aimed at addressing a major gap in knowledge in the regulation of gene expression. This project will be used to enhance teaching and learning at DSU with a focus on mentoring and training freshman and sophomore students. The proposed research experiences will provide access for undergraduate STEM students, mainly from underrepresented minority groups, to participate in advanced cellular, molecular and biophysical investigations at DSU. The early involvement of STEM students in active research will increase the retention and graduation rates in STEM as well as increase the production of highly qualified students for graduate school and the STEM global workforce.The goal of the proposed study is to understand the mechanisms by which CD44 regulates gene expression in the cell. The specific aims of this project are to: 1) characterize protein-protein interactions between CD44 intracytoplasmic domain (ICD) and transcription factors Runx2 and/or p53 in cells and to assess the CD44-mediated functional expression of matrix metalloproteinase 9 gene (MMP-9) in the chick embryo model; and 2) map a CD44-ICD minimal binding domain in the protein-protein interactions with p53 and/or Runx2 and to assess its potential use as a small molecule modulator of the CD44 signaling pathway. This proposal combines in vitro and in vivo cellular, molecular and biophysical experimental approaches to investigate how protein-protein and protein-DNA interactions between the CD44-ICD and transcription factors and gene promoters, respectively, regulate gene expression. Detecting details at the molecular level of this gene regulatory mechanism will provide a potential approach to modulate the expression of such genes and their effects on cell phenotypes and thus behavior in cellular physiology and developmental biology.

历史上的黑人学院和大学本科生计划（HBCU-UP）研究启动奖（RIAs）为HBCU的STEM初级教师提供支持，他们开始建立研究计划，以及职业生涯中期的教师，他们可能在担任行政职务或需要重新定向和重建研究计划后返回教师队伍。教师可以在他们的家乡机构，在NSF资助的中心，在研究密集型机构或在国家实验室进行研究。RIA项目预计将有助于进一步提高教师的研究能力和效率，改善他或她的家乡机构的研究和教学，并让本科生参与研究经验。在美国国家科学基金会的支持下，特拉华州州立大学（DSU）将开展旨在解决基因表达调控知识方面的重大空白的研究。该项目将用于提高教学和学习在DSU的重点是指导和培训大一和大二的学生。拟议的研究经验将为本科生STEM学生提供机会，主要来自代表性不足的少数群体，参加DSU的高级细胞，分子和生物物理研究。STEM学生早期参与积极的研究将提高STEM的保留率和毕业率，并增加研究生院和STEM全球劳动力的高素质学生的产量。拟议研究的目标是了解CD 44调节细胞中基因表达的机制。该项目的具体目的是：1）表征细胞中CD 44胞浆内结构域（ICD）与转录因子Runx 2和/或p53之间的蛋白质-蛋白质相互作用，并评估鸡胚模型中CD 44介导的基质金属蛋白酶9基因（MMP-9）的功能表达;和2）在与p53和/或Runx 2的蛋白质-蛋白质相互作用中定位CD 44-ICD最小结合结构域，并评估其作为CD 44信号传导途径的小分子调节剂的潜在用途。该提案结合了体外和体内细胞，分子和生物物理实验方法，以研究CD 44-ICD与转录因子和基因启动子之间的蛋白质-蛋白质和蛋白质-DNA相互作用如何分别调节基因表达。在分子水平上检测这种基因调控机制的细节将提供一种潜在的方法来调节这些基因的表达及其对细胞表型的影响，从而在细胞生理学和发育生物学中的行为。