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

历史黑人学院和大学-本科项目(HBCU-UP)研究启动奖(RIA)为HBCU的STEM初级教员提供支持，他们开始建立研究项目，以及为职业生涯中期可能在担任行政职位后重返教职队伍或需要重新定向和重建研究项目的教师提供支持。教职员工可以在他们的家乡机构、NSF资助的中心、研究密集型机构或国家实验室进行研究。RIA项目有望帮助教师进一步提高研究能力和效率，改善其所在机构的研究和教学，并让本科生参与研究体验。在国家科学基金会的支持下，特拉华州立大学(DSU)将进行研究，旨在解决基因表达调控方面的重大知识空白。该项目将用于加强该校的教与学，重点是指导和培训一年级和二年级的学生。拟议的研究经验将为STEM本科生提供机会，主要是来自代表人数较少的少数群体的学生，参与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增加STEM的保留率和毕业率，并增加为研究生院和STEM全球劳动力培养的高素质学生。拟议的研究目的是了解CD44调控细胞中基因表达的机制。本项目的具体目的是：1)研究CD44胞质内域(ICD)与细胞中转录因子Runx2和/或P53之间的蛋白-蛋白质相互作用，并评估CD44介导的基质金属蛋白酶9基因(MMP9)在鸡胚胎模型中的功能表达；2)定位CD44-ICD与P53和/或Runx2蛋白相互作用的最小结合域，并评估其作为CD44信号通路小分子调节剂的潜在用途。这一建议结合了体外和体内的细胞、分子和生物物理实验方法，分别研究CD44-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，将为调控这类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提供一种潜在的途径。

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.