Coordination Funds

协调基金

• 批准号: 533618747
• 负责人: Professor Dr. Michael Rieger
• 金额: --
• 依托单位: Klinik 2 - Hämatologie/Onkologie, Rheumatologie und Infektiologie/HIV
• 依托单位国家: 德国
• 项目类别: Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/533618747?language=en
• 关键词: Coordination; Funds

The acquisition of somatic mutations in hematopoietic stem/progenitor cells in myeloid-leukemia-related genes coincides with the normal aging process and leads to the outgrowth of mutated blood cell clones (clonal hematopoiesis, CH). CH is highly prevalent in individuals over the age of 60. Intensive research by us and others over the last 5 years have revealed that CH has major pathophysiological implications. While CH is associated with enhanced risk to progress into hematologic malignancies, CH has emerged as an unexpected, independent risk factor and driver of atherosclerosis, coronary heart disease, heart failure and aortic valve stenosis. The topic of utmost medical interest requires a transdisciplinary Research Unit (entitled HERZBLUT) crossing the boarders of hematology and cardiovascular medicine. We present a strong team of world-leading experts in these fields and emerging junior investigators to pair strong life science and medical research experience with sophisticated technologies and advanced research approaches. Basic and clinician scientists closely interact to transfer the knowledge from molecular and cell-based models to preclinical models and clinical application, and to enable the reverse translation of primary material from well characterized patient cohorts back to the lab. The restriction on certain genes (DNMT3A, TET2, PPM1D, SRSF2, SF3B1), mutations and CH-associated diseases (heart failure, valve stenosis, pulmonary hypertension, acute myeloid leukemia) will generate high synergisms in sharing common technologies, models, and research tools within HERZBLUT, and help to build a broad and unifying picture of overarching disease mechanisms. We propose here a comprehensive and highly synergistic work program to follow two major aims: a) to target the pathomechanisms of CH for therapeutic applications and b) to interrogate CH development and progression in the context of CH-associated diseases. With HERZBLUT, we pursue following objectives: (1) To promote precision biology in the field of CH and its associated diseases of the heart and the blood by studying the molecular and cellular pathomechanisms. (2) To exploit mechanistic findings for novel individualized therapies, promoting precision medicine. (3) To promote junior scientists and clinicians for basic and translational research. (4) To recruit and promote outstanding female scientists and clinicians. (5) To facilitate the development of diagnostic and therapeutic approaches by patenting and exploiting our newly gained knowledge. (6) To install a broad array of measures addressing public outreach for the scientific and medical community and for the general public. The exquisite composition of HERZBLUT, paired with an excellent and stringent research plan, will ensure our efforts in developing critical knowledge and in translating tools for clinical management of CH and CH-associated diseases in the heart and blood.

髓系白血病相关基因的造血干/祖细胞获得体细胞突变符合正常的衰老过程，并导致突变的血细胞克隆(克隆性造血法)的产生。CH在60岁以上的人群中非常普遍。我们和其他人在过去5年的深入研究表明，CH具有重要的病理生理学意义。虽然CH与进展为血液系统恶性肿瘤的风险增加有关，但CH已成为动脉粥样硬化、冠心病、心力衰竭和主动脉瓣狭窄的一个意想不到的独立危险因素和驱动因素。最具医学意义的话题需要一个跨学科的研究单位(名为HERZBLUT)，跨越血液学和心血管医学的边界。我们拥有一支由这些领域世界领先的专家和新兴的初级调查人员组成的强大团队，将强大的生命科学和医学研究经验与尖端技术和先进的研究方法相结合。基础和临床科学家密切互动，将知识从基于分子和细胞的模型转移到临床前模型和临床应用，并使主要材料能够从具有良好特征的患者队列反向转换回实验室。对某些基因(DNMT3A、TET2、PPM1D、SRSF2、SF3B1)、突变和CH相关疾病(心力衰竭、瓣膜狭窄、肺动脉高压、急性髓系白血病)的限制将在HERZBLUT内共享共同技术、模型和研究工具方面产生高度协同效应，并有助于建立一个广泛和统一的总体疾病机制图景。我们在这里提出了一个全面的、高度协同的工作计划，以遵循两个主要目标：a)针对CH的病理机制用于治疗应用，以及b)在CH相关疾病的背景下询问CH的发展和进展。通过HERZBLUT，我们追求以下目标：(1)通过分子和细胞病理机制的研究，促进CH及其相关心脏和血液疾病领域的精确生物学研究。(2)利用机制发现新的个体化治疗方法，促进精准医学。(三)推动初级科学家和临床医生从事基础研究和转化性研究。(四)招录提拔优秀女科学家和临床医生。(5)通过申请专利和利用我们新获得的知识来促进诊断和治疗方法的发展。(6)制定一系列广泛的措施，面向科学界和医学界以及公众进行公众宣传。HERZBLUT的精致组成，加上卓越而严格的研究计划，将确保我们努力开发关键知识，并翻译用于心脏和血液中CH和CH相关疾病的临床管理工具。