Coordination Funds

协调基金

• 批准号: 459600179
• 负责人: Professor Dr. Peter Boor, Ph.D.
• 金额: --
• 依托单位: Institut für Pathologie
• 依托单位国家: 德国
• 项目类别: Clinical Research Units
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/459600179?language=en
• 关键词: Coordination; Funds

Nephrologists treat highly complex patients and at the same time conduct the lowest number of randomized controlled clinical trials (RCTs) in internal medicine. The latter is due to insufficient knowledge of pathophysiology, insufficient preclinical models, and most importantly the lack of accepted surrogate endpoints for RCTs. To address this urgent need, our clinical research unit (CRU) will develop and translate emerging methods that are still largely unexplored in nephrology to better understand the pathophysiology of kidney diseases. By that, we aim to develop new diagnostic approaches, new potential endpoints for RCTs, and ultimately new therapies. In our CRU we synergistically integrate two key features: first, the systematic combination of basic scientists (chemists, biochemists, biologists, electrical engineers, computational biologist, imaging experts) with translational and clinical scientists (nephrologists, nephropathologists) and second, intense interaction between all groups at the methodological level combining complementary expertise, as well as sharing biomaterials and data.We will particularly focus on phase transitions in kidney diseases, i.e. resolution versus progression of renal diseases and the transition from acute to chronic kidney injury. For this, we aim to develop in vitro high throughput humanized 3D models of the tubulointerstitium for modeling and validation of molecular disease mechanisms. We will generate comprehensive molecular maps of kidney disease transitions by applying, further developing, and integrating tissue proteomics and functional genomics focusing on single-cell transcriptomes and epigenomes and develop integrative computational methods for multiomics. We will develop machine learning for digital renal pathology to facilitate robust quantitative and multiparametric analyses, i.e. pathomics. We will also develop and refine our unique methods in molecular imaging and super-resolution ultrasound for non-invasive kidney imaging and disease monitoring. Finally, we aim to integrate these diagnostic methods to better understand human IgA nephropathy, which is particularly difficult to study since no adequate pre-clinical models exist. Our CRU is intricately embedded in and reflects the major research foci of the Medical Faculty of the RWTH Aachen University, namely “Phase Transition in Disease” and “Medical Technology and Digital Life Sciences” and will be an important part of the recently established “Comprehensive Diagnostic Center Aachen” (CDCA).

肾病学家治疗高度复杂的患者，同时进行最少数量的内科随机对照临床试验（RCT）。后者是由于病理生理学知识不足，临床前模型不足，最重要的是RCT缺乏公认的替代终点。为了满足这一迫切需求，我们的临床研究部门（CRU）将开发和翻译肾脏病学中尚未探索的新兴方法，以更好地了解肾脏疾病的病理生理学。因此，我们的目标是开发新的诊断方法，新的RCT潜在终点，并最终开发新的治疗方法。在我们的CRU中，我们协同整合了两个关键功能：第一，基础科学家的系统组合，（化学家、生物化学家、生物学家、电气工程师、计算生物学家、成像专家）与翻译和临床科学家（肾脏病学家，肾脏病理学家）和第二，在方法层面上结合互补的专业知识，以及分享生物材料和数据。我们将特别关注肾脏疾病的相变，即肾脏疾病的消退与进展以及从急性到慢性肾损伤的转变。为此，我们的目标是开发体外高通量人源化的3D模型的tubuloacetitium的分子疾病机制的建模和验证。我们将通过应用，进一步开发和整合组织蛋白质组学和功能基因组学，重点是单细胞转录组和表观基因组，并开发多组学的综合计算方法，来生成肾脏疾病转变的综合分子图谱。我们将为数字肾脏病理学开发机器学习，以促进强大的定量和多参数分析，即病理组学。我们还将开发和完善我们在分子成像和超分辨率超声方面的独特方法，用于非侵入性肾脏成像和疾病监测。最后，我们的目标是整合这些诊断方法，以更好地了解人类伊加肾病，这是特别难以研究，因为没有足够的临床前模型存在。我们的CRU错综复杂地嵌入并反映了RWTH亚琛大学医学院的主要研究重点，即“疾病的相变”和“医疗技术和数字生命科学”，并将成为最近成立的“综合诊断中心亚琛”（CDCA）的重要组成部分。