Periodic Reporting for period 1 - DECODE-DKD (Decoding diabetic kidney disease)
Reporting period: 2022-04-01 to 2024-09-30
Diabetic kidney disease (DKD) poses a significant global health challenge as the leading cause of chronic kidney disease (CKD) and a major contributor to end-stage renal disease (ESRD). With 20% of DKD patients progressing to ESRD, this condition is associated with tremendously increased morbidity and mortality. The pathophysiology of DKD is complex and incompletely understood, and the number of treatment options remains low. The DECODE-DKD project, led by Principal Investigator Christoph Kuppe at the University Hospital RWTH Aachen, Germany, aims to address these issues through a patient-centric research approach.
Our objectives are to create a detailed, spatially resolved molecular map of human DKD, providing deep insights into its pathophysiology, and to identify and dissect therapeutic pathways and signaling networks for new drug target discovery. Additionally, we aim to use patient-derived in-vitro models to validate these targets, ensuring their potential effectiveness in treating DKD. By employing advanced spatial and single-cell molecular techniques, we intend to generate a comprehensive map of DKD at the single-cell level, leading to innovative therapeutic approaches.
The vision of DECODE-DKD is to utilize these novel spatial and single-cell multi-omic technologies to generate a blueprint and predictive model of DKD. This unbiased map will serve to generate testable hypotheses with spatial and temporal coordinates at single-cell resolution. To identify disease-relevant pathways and novel druggable targets, in-vitro and in-vivo genome editing approaches will be employed, combined with high-throughput screens. In-vitro assays with human-derived kidney organoids will be used to screen potential compounds, facilitating the development of novel therapeutics. This highly ambitious interdisciplinary proposal requires the expertise of biomedical engineers, computational biologists, biomedical researchers, and physician-scientists. The knowledge and outcomes generated by DECODE-DKD will be transformative, providing a significant step forward towards novel drug targets and precision medicine for the treatment of diabetic kidney disease using a systems medicine approach.
Our objectives are to create a detailed, spatially resolved molecular map of human DKD, providing deep insights into its pathophysiology, and to identify and dissect therapeutic pathways and signaling networks for new drug target discovery. Additionally, we aim to use patient-derived in-vitro models to validate these targets, ensuring their potential effectiveness in treating DKD. By employing advanced spatial and single-cell molecular techniques, we intend to generate a comprehensive map of DKD at the single-cell level, leading to innovative therapeutic approaches.
The vision of DECODE-DKD is to utilize these novel spatial and single-cell multi-omic technologies to generate a blueprint and predictive model of DKD. This unbiased map will serve to generate testable hypotheses with spatial and temporal coordinates at single-cell resolution. To identify disease-relevant pathways and novel druggable targets, in-vitro and in-vivo genome editing approaches will be employed, combined with high-throughput screens. In-vitro assays with human-derived kidney organoids will be used to screen potential compounds, facilitating the development of novel therapeutics. This highly ambitious interdisciplinary proposal requires the expertise of biomedical engineers, computational biologists, biomedical researchers, and physician-scientists. The knowledge and outcomes generated by DECODE-DKD will be transformative, providing a significant step forward towards novel drug targets and precision medicine for the treatment of diabetic kidney disease using a systems medicine approach.
The DECODE-DKD project has made significant progress toward its objectives, demonstrating our commitment to advancing the understanding and treatment of diabetic kidney disease (DKD) through innovative research and collaboration. We have successfully developed spatial transcriptomics, allowing us to map gene expression within tissue samples and providing a detailed view of the molecular landscape of DKD. Additionally, the implementation of protein MERFISH co-profiling enables the simultaneous visualization of RNA and protein within the same tissue section, offering comprehensive insights into cellular states and interactions. We have established a cutting-edge research laboratory dedicated to high-resolution spatial imaging and analysis, significantly enhancing our research capabilities. Through the generation of extensive high-quality datasets from human kidney biopsies, we have gained valuable insights into the molecular mechanisms of DKD. Furthermore, we have initiated successful collaborations with various partners to translate our research findings into practical applications, thereby accelerating the development of new therapies for DKD.
The DECODE-DKD project has achieved several milestones that push the boundaries of current diabetic kidney disease (DKD) research, with significant potential impacts that pave the way for innovative therapeutic approaches. Our breakthrough methodologies, including the development of spatial transcriptomics and protein MERFISH co-profiling, represent substantial advancements in spatial biology. These techniques enable high-resolution, multi-dimensional mapping of molecular interactions within tissues, providing unprecedented insights into the cellular and molecular landscapes of DKD.
By generating high-quality datasets from human kidney biopsies, we have identified key molecular pathways and potential therapeutic targets. This detailed molecular understanding is crucial for developing targeted therapies that can effectively treat DKD. Additionally, the establishment of a state-of-the-art research lab dedicated to high-resolution spatial imaging and analysis has significantly enhanced our research capabilities, positioning us at the forefront of DKD research and enabling us to conduct cutting-edge experiments.
Our collaborations with various partners have been instrumental in translating our research findings into practical applications, accelerating the development of new therapies for DKD and demonstrating the potential for real-world impact. The integration of expertise from biomedical engineers, computational biologists, biomedical researchers, and physician-scientists has been crucial in advancing the project, ensuring that our research is comprehensive and addresses multiple aspects of DKD pathophysiology and treatment.
By generating high-quality datasets from human kidney biopsies, we have identified key molecular pathways and potential therapeutic targets. This detailed molecular understanding is crucial for developing targeted therapies that can effectively treat DKD. Additionally, the establishment of a state-of-the-art research lab dedicated to high-resolution spatial imaging and analysis has significantly enhanced our research capabilities, positioning us at the forefront of DKD research and enabling us to conduct cutting-edge experiments.
Our collaborations with various partners have been instrumental in translating our research findings into practical applications, accelerating the development of new therapies for DKD and demonstrating the potential for real-world impact. The integration of expertise from biomedical engineers, computational biologists, biomedical researchers, and physician-scientists has been crucial in advancing the project, ensuring that our research is comprehensive and addresses multiple aspects of DKD pathophysiology and treatment.