Cardiovascular Immunology Research Core (Core B)

心血管免疫学研究核心（核心B）

• 批准号: 10625951
• 负责人: Zhijian J Chen
• 金额: $ 24.6万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-05 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10625951
• 关键词: Adaptor Signaling Protein; Adult; Antibodies; Antigen-Antibody Complex; Binding; Biological Process; Cardiac; Cardiac Myocytes; Cardiovascular system; Cell Aging; Cell Cycle Arrest; Cells; Cessation of life; Chromium; Complex; Consultations; Cyclic GMP; DNA; Data Analyses; Digestion; Enzymes; Equipment; Failure; Flow Cytometry; Gene Expression Profiling; Generations; Genomics; Goals; Growth; Heart; Heart failure; Hyperplasia; Hypertrophy; Immune; Immune response; Immunologics; Immunologist; Immunology; Immunology procedure; Inflammatory Response; Injury; Innate Immune Response; Interferon Type I; Interferons; Isomerism; Life; Link; Logistics; Macrophage; Mediating; Medical center; Modeling; Myocardial; Natural Immunity; Natural regeneration; Neonatal; Pathway interactions; Play; Process; Production; Productivity; Proliferating; Reagent; Regulation; Rejuvenation; Research; Research Design; Research Personnel; Resource Allocation; Resources; Role; Second Messenger Systems; Services; Signal Transduction; Stimulator of Interferon Genes; T-Lymphocyte; Technical Expertise; Techniques; Therapeutic; Tissues; Tumor Immunity; Ventricular Remodeling; Virus; Western Blotting; design; experience; gain of function; healing; immunocytochemistry; inhibitor; innovation; interest; loss of function; meetings; member; postnatal; prevent; programs; response to injury; sensor; single-cell RNA sequencing; skills; success; synergism

Heart failure progression is a complex biological process that is precipitated by the maladaptive myocardial response to injury, compounded by failure of the adult heart to replace lost or damaged cardiomyocytes. Conceivably, identifying common pathways that regulate these two seemingly unrelated processes would profoundly impact therapeutic strategies to prevent, and even reverse heart failure progression. Numerous observations by members of the proposed consortium and others support the notion that the endogenous capacity of the neonatal mammalian heart to proliferate fades in the early postnatal life as a switch from hyperplastic to hypertrophic growth of cardiomyocytes takes place. Members of the proposed consortium and others have also previously demonstrated that mechanisms linked to activation of innate immune response may play a role in cardiomyocyte hypertrophy, death and even stimulation of new cardiomyocyte generation. However, whether mechanisms involved in cardiomyocyte cell cycle arrest also play a role in the maladaptive cardiomyocyte response to injury is not known. Indeed, critical components of the inflammatory response appear to underlie both cardiac rejuvenation after injury through positive effects on healing, as well as stimulating cardiomyocytes to proliferate. Therefore, the current proposal brings together 5 groups with expertise in myocardial remodeling, regeneration and immunology with the overall goal of determining the role of immune response signaling in regulation of cardiac growth and regeneration. The 4 Project Leaders are cardiovascular biologist, and thus having a strong immunology presence in the network is paramount for its success, not only to provide technical expertise and reagents, but also to play a crucial consultancy role. Core B will be led by Dr. James Chen, a renowned immunologist, who will play the critical role of providing technical and logistic support to Project Leaders in all matters pertaining to immunological studies. This is a critical and innovative design of the current Program Project as it will allow the 4 Project leaders to seamlessly integrate complex immunological assays and concepts into their research program. As such, Core B will provide a number of essential support services including isolation and characterization of immune cells, performing gene expression analysis studies, providing critical reagents for immunological assays and providing consultation on study design and interpretation. The immunology goal will serve an invaluable role within the network that will enhance synergy, and maximize productivity of all Network Projects

心力衰竭进展是一个复杂的生物过程，由心肌适应不良引起 对损伤的反应，加上成人心脏无法替代丢失或受损的心肌细胞。 可以想象，确定调节这两个看似无关的过程的共同途径将 深刻影响预防甚至逆转心力衰竭进展的治疗策略。很多的 拟议联盟成员和其他人的意见支持以下观点：内生性 新生哺乳动物心脏的增殖能力在出生后早期随着从心脏功能的转变而减弱 心肌细胞发生增生性肥大生长。拟议财团的成员以及 其他人之前也证明了与先天免疫反应激活相关的机制可能 在心肌细胞肥大、死亡甚至刺激新心肌细胞中发挥作用 一代。然而，参与心肌细胞细胞周期停滞的机制是否也在心肌细胞细胞周期停滞中发挥作用。 心肌细胞对损伤的适应不良反应尚不清楚。事实上，炎症的关键成分 通过对愈合的积极影响，反应似乎是受伤后心脏恢复活力的基础 因为刺激心肌细胞增殖。因此，目前的提案汇集了 5 个小组 心肌重塑、再生和免疫学方面的专业知识，总体目标是确定其作用 免疫反应信号在心脏生长和再生调节中的作用。 4位项目负责人分别是 心血管生物学家，因此在网络中拥有强大的免疫学存在对其至关重要 成功，不仅提供了技术专业知识和试剂，而且还发挥了至关重要的咨询作用。核 B将由著名免疫学家James Chen博士领导，他将在提供技术方面发挥关键作用 就与免疫学研究有关的所有事项向项目负责人提供后勤支持。这是一个关键且 当前计划项目的创新设计，因为它将允许 4 名项目负责人无缝集成 将复杂的免疫学测定和概念纳入他们的研究计划中。因此，Core B 将提供 一些基本支持服务，包括免疫细胞的分离和表征、执行基因 表达分析研究，为免疫学测定提供关键试剂并提供咨询 研究设计和解释。免疫学目标将在网络中发挥不可估量的作用， 增强协同效应，最大限度地提高所有网络项目的生产力