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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

基本信息

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
项目类别：
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

项目摘要

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.

项目总结