Research
SINGle-cell mapping of Living kidney donation for the Assessment of Renal adaptation (SINGuLAR)
Although the kidney has a remarkable capacity for adaptation and recovery, previous studies have focused mainly on injury signatures. As a result, promising treatments that were effective in animal models have failed in humans. Investigations that directly address the kidney’s adaptive mechanisms are still lacking - primarily because adaptation signals are masked by the noise of injury and inflammation. SINGuLAR therefore makes use of a unique human model: living kidney donors permanently lose 50% of their renal mass, yet the remaining kidney shows striking compensatory growth and functional adaptation - free from disease-related confounders. We study these adapting kidney cells and, for the first time, generate a prospective single-cell map of kidney adaptation. In addition, we investigate epigenetic regulatory mechanisms, spatial and temporal patterns, and the relationship between donor adaptation and transplant outcomes. SINGuLAR aims to provide fundamental insights into the natural regeneration of the human kidney and to open new avenues for therapeutically harnessing these mechanisms in the future.
The project is funded by the European Research Council (ERC Starting Grant).
Spatial Pattern Identification of Reperfusion and Ischemia of the Kidney (SPIRIT-K)
The kidney has a complex anatomical architecture composed of more than 30 specialized cell types. Novel approaches such as transcriptome and epigenome sequencing at the single-cell level (sc/snRNA-seq, snATAC-seq) provide unprecedented insight into the molecular and cellular composition of healthy and diseased kidneys. However, these methods rely on tissue dissociation and remove the spatial context of the cellular niche (microenvironment). In contrast, spatial transcriptomics enables the readout of cell type-specific transcription while simultaneously preserving information on tissue organization. To date, no comprehensive spatial map exists that differentiates shared and specific pathophysiological features before, during, and after ischemia/reperfusion in human kidney samples. SPIRIT-K aims to fill this gap.
The project is supported by the Dr. Werner Jackstädt Foundation and the Sonnenfeld Foundation.
Endophenotypes in Acute Kidney Injury (AKI)
Acute kidney injury (AKI), despite the kidney’s immense reparative capacity, often progresses to chronic kidney disease affecting more than 850 million people worldwide. Currently, there are no drugs that can prevent or halt the decline in kidney function following acute damage. Modern single-cell analytical techniques hold the potential to fundamentally transform our understanding of disease processes at the cellular level. This project aims to identify cellular signatures, so-called endophenotypes that distinguish successful organ repair from maladaptive regeneration leading to fibrosis. By doing so, it seeks to challenge traditional paradigms in the characterization of kidney diseases and lay the foundation for the development of targeted therapies for AKI.
The project is supported by the Else Kröner-Fresenius Foundation, the German Academic Exchange Service (DAAD), and the Sonnenfeld Foundation.
