Project Details
Projekt
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
Nephrology cares for highly complex patients and at the same time has the lowest number of randomized controlled clinical trials (RCTs) in internal medicine. The latter is largely due to an insufficient understanding of pathophysiology, relevant preclinical models, specific diagnostic approaches, and accepted surrogate endpoints for RCTs. Our clinical research unit (CRU) addresses this unmet need by developing and translating emerging methods to improve kidney research. Our diverse and highly complementary set of expertise, techniques, and approaches enables us to test novel diagnostic approaches, that could serve as potential endpoints for RCTs and advance our understanding of the driving mechanisms and regulatory processes of kidney disease transitions of stable vs. progressive vs. recovery states. Examples of our achievements from the 1st funding period include a novel omics approach for kidney histology, termed pathomics, which was coined as one of the major achievements in nephrology in 2023; advanced human kidney organoid models to study kidney diseases, including the effects of SARS-CoV-2; development of approaches generating spatial multi-omics maps in human tissues; or the refinement of non-invasive kidney imaging. In the 2nd funding period, our goals centre around four areas: novel in vitro humanized models, omics technologies for morphological and molecular characterization of kidney tissues, non-invasive imaging approaches, and data and methods integration. Two projects (P) will develop humanized in vitro models, focusing on high-throughput and functionalized organoids to test mechanisms and drugs (P1 and P10). Three projects will utilize complementary approaches of spatial transcriptomics (P2), spatial proteomics (P3), and pathomics (P4), to generate comprehensive morpho-molecular maps of kidney disease transitions. Two projects will develop non-invasive imaging methods, i.e. molecular imaging (P6) and super-resolution ultrasound (P7) for improved diagnostics, disease monitoring, and theranostic. Finally, two projects will focus on developing approaches to integrate these technologies and diagnostics to advance our understanding of the pathophysiology of IgA nephropathy (P8) and kidney side-effects of drugs or environmental toxins, including the CKD of unknown origin, an enigmatic global health issue (P9). Structurally, our CRU is deeply embedded and strengthens the major research foci of the Medical Faculty of the RWTH Aachen University, i.e., “Phase Transition in Disease” and “Medical Technology and Digital Life Sciences” and the Profile Area “Medicine and Technology” of the RWTH Aachen University. Our CRU is integrated within the “Comprehensive Diagnostic Centre Aachen – CDCA” and the “Centre for Computational Life Sciences – CCLS”. Two research buildings, currently under construction, will provide extensive added infrastructural support for the CRU.
DFG Programme
Clinical Research Units
Projects
- Advanced ex vivo human kidney disease models using induced pluripotent stem cells (Applicants Kramann, Rafael ; De Laporte, Laura )
- Altered cellular compartmentalization as a potential pathomechanism driving CKD. (Applicants Antonin, Wolfram ; Möller, Marcus )
- Cell-state specific tissue proteomes in AKI (Applicants Jankowski, Vera ; Saritas, Turgay )
- Coordination Funds (Applicant Boor, Ph.D., Peter )
- Development of high-throughput platforms for human kidney disease modeling. (Applicants Kramann, Rafael ; De Laporte, Laura )
- Dissecting regulatory programs of kidney disease with functional genomics (Applicants Gesteira Costa Filho, Ivan ; Kuppe, Christoph )
- Exploring the Kidney Immune Cell Crosstalk using functionalized kidney organoids, transcriptomics and advanced morphometrics (Applicants Schneider-Kramann, Rebekka ; von Stillfried, Saskia )
- Identification of non-invasive biomarkers for CKD transitions with super-resolution ultrasound (Applicants Fleig, Susanne ; Kiessling, Fabian ; Schmitz, Georg )
- Integrative assessment of kidney tissue toxicity (Applicants Stingl, Julia ; Vervaet, Ph.D., Benjamin )
- Integrative high-resolution multi-omics and targeted approaches in patients with IgAN (Applicants Hayat, Sikander ; Pabst, Oliver ; Seikrit, Claudia )
- Modulation of tubular cell transition to a regenerative phenotype in AKI - diagnostic and therapeutic implications (Applicants Jankowski, Vera ; Stamellou, Ph.D., Eleni )
- Next-generation morphometry and pathomics for nephropathology (Applicants Boor, Ph.D., Peter ; Kobbelt, Leif )
- Theranostic targeting of renal myofibroblasts (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 )
Project Heads
Dr. Susanne Fleig; Professor Dr. Ivan Gesteira Costa Filho; Dr. Sikander Hayat; Professorin Dr. Vera Jankowski; Professor Dr. Fabian Kiessling; Dr. Barbara Mara Klinkhammer; Professor Dr. Leif Kobbelt; Professor Dr. Rafael Kramann; Professor Dr. Christoph Kuppe; Professor Dr. Twan Lammers; Professorin Dr.-Ing. Laura De Laporte; Professor Dr. Felix Mottaghy; Professor Dr. Oliver Pabst; Privatdozent Dr. Turgay Saritas; Professor Dr.-Ing. Georg Schmitz; Professorin Dr. Rebekka Schneider-Kramann; Dr. Claudia Seikrit; Dr. Saskia von Stillfried; Professorin Dr. Julia Stingl; Professor Dr. Benjamin Vervaet, Ph.D.
