Catalyst Award: "Characterization of p27Kip1 as an Enhancer of Stem-Like Properties in Breast Cancer Stem Cells"

催化剂奖：“p27Kip1 作为乳腺癌干细胞干细胞样特性增强剂的表征”

• 批准号: 2100655
• 负责人: Erica Cassimere
• 金额: $ 14.99万
• 依托单位: Texas Southern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2100655&HistoricalAwards=false
• 关键词: Catalyst; Award; Characterization; p27Kip1; Enhancer

Catalyst Awards provide support for junior and mid-career faculty at Historically Black Colleges and Universities who are building new research programs or redirecting and rebuilding existing research programs. It is expected that the award helps to further the faculty member's research capability and effectiveness, improve research and teaching at the home institution, and involves undergraduate students in research experiences. The award to Texas Southern University intends to understand the molecular mechanisms by which an enzyme inhibitor enhances the stem cell populations found in breast cancer stem cells. Undergraduate students will be involved in this work through participation in a 10-week intensive summer experience.The overall goal of this project is to identify the molecular mechanisms by which the cell cycle kinase inhibitor, p27KIP1 (termed p27), enhances stem cell populations found in breast cancer stem cells (CSCs). Texas Southern University undergraduate students will employ various in vitro cellular and molecular biology assays to perform research. The proposed study will characterize p27 protein expression in CSCs compared to non-CSCs isolated from breast cancer cell lines with different molecular signatures. Protein expression for p27 will be assessed by Western blot analysis. The subcellular compartment whereby p27 resides will be investigated using fluorescence microscopy to shed light on the role of p27 in the stemness of these populations, for p27 exerts both cell cycle-dependent (nuclear) and cell-cycle independent (cytoplasmic) functions. Moreover, the molecular factors which contribute to p27 stability in breast CSCs will be determined using cell lines stably expressing p27 with point substitutions at residues known to regulate p27 protein expression. Investigating novel biological markers involved in the stem cell niche will enhance our understanding of the factors governing stemness as identification of reliable breast cancer stem markers still remains a challenge. The implementation of this proposal will provide a unique opportunity for underrepresented minority STEM majors to be immersed in hands-on research experiences using cutting edge techniques and prepare them for graduate programs and/or careers in the STEM field.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

催化剂奖为历史悠久的黑人学院和大学的初级和中期职业教师提供支持，他们正在建立新的研究项目或重新指导和重建现有的研究项目。期望该奖项有助于提高教师的研究能力和效率，改善所在机构的研究和教学，并使本科生参与研究经验。该奖项授予德克萨斯南方大学，旨在了解酶抑制剂增强乳腺癌干细胞中发现的干细胞数量的分子机制。本科生将通过参加为期10周的暑期密集体验来参与这项工作。该项目的总体目标是确定细胞周期激酶抑制剂p27KIP1（称为p27）增强乳腺癌干细胞（CSCs）中发现的干细胞群的分子机制。德克萨斯南方大学的本科生将使用各种体外细胞和分子生物学分析来进行研究。拟议的研究将表征p27蛋白在CSCs中的表达，并将其与从不同分子特征的乳腺癌细胞系中分离的非CSCs进行比较。Western blot检测p27蛋白表达。我们将使用荧光显微镜研究p27所在的亚细胞区室，以阐明p27在这些群体的干性中的作用，因为p27同时发挥细胞周期依赖（核）和细胞周期独立（细胞质）的功能。此外，有助于乳腺CSCs中p27稳定性的分子因子将通过稳定表达p27的细胞系，在已知的调节p27蛋白表达的残基上进行点替换来确定。由于确定可靠的乳腺癌干细胞标记物仍然是一个挑战，研究涉及干细胞生态位的新生物标记物将增强我们对控制干细胞的因素的理解。该提案的实施将为代表性不足的少数族裔STEM专业学生提供一个独特的机会，让他们沉浸在使用尖端技术的实践研究经验中，并为他们在STEM领域的研究生课程和/或职业生涯做好准备。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。