KFO 5011:  Integrating emerging methods to advance translational kidney research (InteraKD)

• Subject Area: Medicine
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 445703531

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).

• DFG Programme: Clinical Research Units

Projects

• Altered cellular compartmentalization as a potential pathomechanism driving CKD. (Applicants Antonin, Wolfram ;  Möller, Marcus )
• Coordination Funds (Applicant Boor, Ph.D., Peter )
• Deep learning and pathomics augmented nephropathology (Applicants Boor, Ph.D., Peter ;  Merhof, Dorit )
• Development of high-throughput platforms for human kidney disease modeling. (Applicants Kramann, Rafael ;  De Laporte, Laura )
• Dissecting IgA nephropathy via integration of multi-omics data (Applicants Saez-Rodriguez, Julio ;  Seikrit, Claudia )
• Dissecting regulatory programs of kidney disease transition using functional genomics (Applicants Gesteira Costa Filho, Ivan ;  Kuppe, Christoph )
• Modulation of tubular cell transition to a regenerative phenotype in AKI - diagnostic and therapeutic implications (Applicants Jankowski, Ph.D., Vera ;  Stamellou, Ph.D., Eleni )
• Molecular imaging of tissue remodeling in CKD (Applicants Klinkhammer, Barbara Mara ;  Lammers, Twan ;  Mottaghy, Felix )
• Understanding and monitoring renal microvascular remodeling in CKD by super-resolution ultrasound. (Applicants Kiessling, Fabian ;  Klinkhammer, Barbara Mara ;  Schmitz, Georg )

• Spokesperson: Professor Dr. Peter Boor, Ph.D.
• Leader: Professor Dr. Marcus Möller
• Project Heads: Professor Dr. Wolfram Antonin; Dr. Sonja Djudjaj; Professor Dr. Jürgen Floege; Professor Dr. Ivan Gesteira Costa Filho; Professorin Dr. Vera Jankowski, Ph.D.; Professor Dr. Fabian Kiessling; Professor Dr. Rafael Kramann; Professor Dr. Christoph Kuppe; Professor Dr. Twan Lammers; Professorin Dr.-Ing. Laura De Laporte; Professorin Dr.-Ing. Dorit Merhof; Professor Dr. Felix Mottaghy; Professor Dr.-Ing. Julio Saez-Rodriguez; Professor Dr.-Ing. Georg Schmitz; Dr. Eleni Stamellou, Ph.D.