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

硫化氢(H_2S)是最近出现的一种人体必需分子。有证据表明，硫化氢在癌症、阿尔茨海默病和心脏病等脑部疾病中发挥着重要作用。深入了解硫化氢在生物学中的作用可能会导致开发新的治疗方法来治疗这些疾病。这个职业项目使用聚合物纳米反应器来开发工具，以促进对人体内硫化氢的基本了解。教育活动的重点是吸引各级学生，特别是女性和代表性不足的少数族裔学生，在生物材料科学领域发展职业道路，并通过参与女孩研究我们的世界(Growth)计划和在KSU开发一门新的生物材料课程，为堪萨斯州立大学(KSU)的教育使命做出贡献。硫化氢(H_2S)是一种气体信号传递分子，在调节心血管、神经系统、免疫系统和癌症等方面发挥着重要作用。虽然已经做出了重大努力来促进对硫化氢生物学的基本了解，但其生物学活动的潜在机制在很大程度上仍然不清楚。最近的研究表明，硫化氢在体内可以被酶氧化或非酶氧化，从而导致多种活性硫物种(RSS)的形成。这些受体被认为是许多与H_2S相关的信号通路的实际介体。因此，迫切需要探索RSS的生物学作用。这个NSF职业项目专注于基于聚合物纳米材料的平台的开发，以提供来自硫化氢的RSS，以探索硫化氢信号的生物学意义。该方法将是设计释放硫化氢的聚合物纳米材料，然后通过模拟生物系统中的硫化氢代谢将其转化为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。预计拟议的技术将提供RSS交付工具，以促进对RSS生物学活动的基本了解。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程序的工作提供基础。该职业奖项由化学、生物工程、环境和运输系统部门的细胞和生化工程计划以及既定的激励竞争研究计划(EPSCoR)共同资助。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.