Probing the cardioprotective effects of sulfane sulfurs with next generation fluorescent sensors

使用下一代荧光传感器探讨硫烷硫的心脏保护作用

• 批准号: 10749202
• 负责人: Meg Shieh
• 金额: $ 4.77万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10749202
• 关键词: Address; Advanced Development; Animal Model; Autophagocytosis; Award; Biological; Biological Assay; Biological Availability; Biological Markers; Biological Models; Biological Phenomena; Biology; Blood; Cardiac; Cardiovascular Diseases; Cardiovascular Pathology; Cardiovascular system; Cell model; Cells; Cellular biology; Chemicals; Clinical; Complex; Confocal Microscopy; Data; Data Science; Detection; Development; Diagnostic; Disease; Educational process of instructing; Environment; Evaluation; Exhibits; Exposure to; Fellowship; Flow Cytometry; Fluorescence; Fluorescence Microscopy; Fluorescent Dyes; Future; Goals; Health; Heart Diseases; Heart failure; Homeostasis; Hydrogen Sulfide; In Vitro; Individual; Institution; Knowledge; Lasers; Leadership; Liquid substance; Machine Learning; Maps; Mediating; Methods; Modification; Molecular Biology; Myocardial Ischemia; Myocardial Reperfusion Injury; Organelles; Organic Chemistry; Organic Synthesis; Oxidants; Oxidation-Reduction; Oxidative Stress; Pathway interactions; Plasma; Positioning Attribute; Procedures; Protocols documentation; Recording of previous events; Reperfusion Therapy; Role; Signaling Molecule; Sincalide; Specificity; Sulfur; System; Testing; Therapeutic; Tissues; Training; Tube; Universities; Work; biological systems; cardioprotection; cardiovascular disorder therapy; career; certificate program; combat; commercialization; cytotoxicity; design; detection method; diagnostic tool; ethnic disparity; fluorophore; gender disparity; human disease; improved; near infrared dye; next generation; novel; outreach; oxidative damage; prevent; professor; quantum; ratiometric; response; sensor; skills; symposium; therapeutic target; thioester; tool

Project Summary Redox imbalances of reactive sulfur species (RSS) in cardiac cells contribute to cardiovascular diseases such as myocardial ischemia-reperfusion (MI/R) injury and heart failure. Applications of sulfane sulfurs have been found to cause cardioprotective effects, and sulfane sulfur bioavailability in plasma has even been recently suggested to be a biomarker for cardiovascular disease (CVD). However, this field currently lacks clear understandings as to how endogenous RSS, particularly sulfane sulfurs, work. Our long-term goal is to elucidate the complex sulfane sulfur pathways at various health stages of cardiac cells and use this information to drive the development of early diagnostic tools and therapies for CVD. Specifically, this project will meet the critical need of having effective methods to study these pathways by developing chemical tools that: 1) quantifiably ‘see into cells/tissues’ despite the presence of biological fluids such as blood and 2) turn-on only after subcellular localization. These highly sensitive, specific, and targetable/triggerable next generation fluorescent sensors will allow us to probe the cardioprotective roles of sulfane sulfurs in cardiac cell models of MI/R injury even to subcellular extents and non-invasively decipher complex cardiovascular sulfur-mediated redox pathways. We expect that: 1) promising sensors will be identified for future evaluations in animal models of MI/R and 2) our tools and studies will establish a strong basis for advancing the clinical potential of sulfane sulfurs through a greater understanding of the mechanisms by which sulfane sulfurs regulate redox environments in CVD. The long-term goal for this fellowship award is to develop essential skills for a successful career as a chemical biology professor studying human diseases at an R1 institution. A team consisting of the sponsor and collaborators has been assembled with expertise in organic chemistry and synthesis, redox biology, chemical biology, molecular and cell biology, computational/data sciences, and cardiovascular diseases. Further training will be obtained from conference attendance and presentations in conjunction with teaching certificate programs, outreach, and leadership positions at Brown University.

项目概要 心肌细胞中活性硫物质 (RSS) 的氧化还原失衡有助于 心血管疾病，例如心肌缺血再灌注（MI/R）损伤和心力衰竭。 已发现硫烷硫的应用可引起心脏保护作用，硫烷 血浆中硫的生物利用度最近甚至被建议作为以下生物标志物： 然而，该领域目前对如何预防心血管疾病缺乏明确的认识。 内源性 RSS，特别是硫烷硫，能够发挥作用，我们的长期目标是阐明其作用。 心肌细胞各个健康阶段的复杂硫烷硫途径并使用此信息 具体而言，该项目旨在推动 CVD 早期诊断工具和疗法的开发。 将满足通过开发有效方法来研究这些途径的迫切需要 化学工具：1）尽管存在生物液体，但仍可量化地“洞察细胞/组织” 例如血液和 2) 仅在亚细胞定位后才开启这些高度敏感、特异性、 可靶向/可触发的下一代荧光传感器将使我们能够探测 硫烷硫在 MI/R 损伤甚至亚细胞损伤的心肌细胞模型中的心脏保护作用 程度并非侵入性地破译复杂的心血管硫介导的氧化还原途径。 预计：1）将确定有前途的传感器用于 MI/R 动物模型的未来评估 2）我们的工具和研究将为提高临床潜力奠定坚实的基础 通过更好地了解硫烷硫的机制来研究硫烷硫 该奖学金的长期目标是调节 CVD 中的氧化还原环境。 作为研究人类疾病的化学生物学教授成功职业生涯的基本技能 在 R1 机构，由赞助商和合作者组成的团队已组建完毕。 有机化学与合成、氧化还原生物学、化学生物学、分子和细胞方面的专业知识 生物学、计算/数据科学和心血管疾病将是进一步的培训。 参加会议和演讲并结合教学证书获得 布朗大学的项目、外展和领导职位。