CAREER: Understanding the biological functions of the gasotransmitter hydrogen sulfide using a polymer engineering approach

职业：利用聚合物工程方法了解气体递质硫化氢的生物功能

• 批准号: 1944390
• 负责人: Urara Hasegawa
• 金额: $ 50.13万
• 依托单位: Kansas State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1944390&HistoricalAwards=false
• 关键词: CAREER; Understanding; biological; functions; gasotransmitter

Hydrogen sulfide (H2S), has recently emerged as an essential molecule in the body. Evidence suggest that H2S plays important roles in cancer, brain diseases, such as Alzheimer’s disease, and heart disease. An in-depth understanding of the function of H2S in biology could lead to development of novel therapeutic approaches to treat these diseases. This CAREER project uses polymeric nanoreactors to develop tools to advance the fundamental understanding of H2S in the human body. The educational activities are focused on engaging students at all levels, with a special emphasis on women and underrepresented minority students, to develop career paths in biomaterials science, and contribute to the educational mission of Kansas State University (KSU) by participating in the Girls Researching Our World (GROW) program and developing a new Biomaterials course at KSU. Hydrogen sulfide (H2S) is a gaseous signal-transmitter molecule (gasotransmitter), which plays a pivotal role in regulating the cardiovascular, nervous system, immune system, and cancer. While significant efforts have been made to advance the basic understanding of H2S biology, the mechanisms underlying its biological activities remains largely unknown. Recent studies have shown that H2S can be oxidized either enzymatically or non-enzymatically in the body, which leads to the formation of diverse reactive sulfur species (RSS). These RSS are suggested to be the actual mediators in many H2S-related signaling pathways. Therefore, there is a critical need to explore the biological roles of RSS. This NSF CAREER project focuses on the development of polymeric nanomaterial-based platforms to deliver H2S-derived RSS to explore the biological significance of H2S signaling. The approach will be to engineer polymeric nanomaterials that release H2S and subsequently convert it to RSS by mimicking H2S metabolism in biological systems. The developed polymeric platforms will be used to determine the physiological and pathological roles of RSS in angiogenesis and tumor growth. The proposed technology is expected to provide RSS delivery tools to advance the fundamental understanding of the biological activities of RSS. Furthermore, it is expected that the obtained knowledge could provide the basis for future work to develop new therapeutic and diagnostic applications for diseases such as cancer.This CAREER award is jointly funded by the Cellular and Biochemical Engineering Program of the Chemical, Bioengineering, Environmental, and Transport Systems Division, and by the Established Program to Stimulate Competitive Research (EPSCoR).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.

硫化氢（H2S），最近已成为人体内的一种重要分子。有证据表明，H2S在癌症、脑疾病（如阿尔茨海默病）和心脏病中起着重要作用。深入了解H2S在生物学中的功能可能会导致开发新的治疗方法来治疗这些疾病。这个CAREER项目使用聚合物纳米反应器来开发工具，以促进对人体中H2S的基本理解。教育活动的重点是吸引各级学生，特别强调妇女和代表性不足的少数民族学生，以发展生物材料科学的职业道路，并通过参与女孩研究我们的世界（GROW）计划和开发新的生物材料课程，为堪萨斯州立大学（KSU）的教育使命做出贡献。 硫化氢（H2S）是一种气体信号传递分子（gasotransmitter），在调节心血管、神经系统、免疫系统和癌症中起着关键作用。虽然已经做出了重大努力来推进对H2S生物学的基本理解，但其生物活性的机制在很大程度上仍然未知。最近的研究表明，H2S可以在体内被酶促或非酶促氧化，从而形成多种活性硫物种（RSS）。这些RSS被认为是许多H2S相关信号通路中的实际介质。因此，迫切需要探索RSS的生物学作用。这个NSF CAREER项目的重点是开发基于聚合物纳米材料的平台，以提供H2S衍生的RSS，以探索H2S信号的生物学意义。该方法将是设计释放H2S的聚合物纳米材料，随后通过模拟生物系统中的H2S代谢将其转化为RSS。开发的聚合物平台将用于确定RSS在血管生成和肿瘤生长中的生理和病理作用。拟议的技术预计将提供RSS传递工具，以推进RSS的生物活性的基本理解。此外，预计所获得的知识可以为未来开发癌症等疾病的新治疗和诊断应用提供基础。该CAREER奖由化学，生物工程，环境和运输系统部门的细胞和生物化学工程项目共同资助，激励竞争研究计划（EPSCoR）该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的评估被认为值得支持。影响审查标准。