A5063686193- Renal Diseases and Glomerulopathies
- Renal and related cancers
- Parkinson's Disease Mechanisms and Treatments
- Neurological disorders and treatments
- Genetic and Kidney Cyst Diseases
- Nuclear Receptors and Signaling
- Genetic Neurodegenerative Diseases
- Chronic Kidney Disease and Diabetes
- Renal Transplantation Outcomes and Treatments
- Complement system in diseases
- COVID-19 Clinical Research Studies
- Herpesvirus Infections and Treatments
- RNA Research and Splicing
- Organ Donation and Transplantation
- Renal cell carcinoma treatment
- Hippo pathway signaling and YAP/TAZ
- Single-cell and spatial transcriptomics
- Neurological Complications and Syndromes
- Birth, Development, and Health
- Polyomavirus and related diseases
- Parvovirus B19 Infection Studies
- Liver Disease and Transplantation
- Organ Transplantation Techniques and Outcomes
- Cytomegalovirus and herpesvirus research
- Melanoma and MAPK Pathways
University of Cologne
2015-2025
University Hospital Cologne
2015-2025
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2020-2025
Centrum für Integrierte Onkologie
2023-2024
RELX Group (United States)
2018
Institute of Occupational Medicine
2017
Boston Children's Hospital
2012-2015
Harvard University
2000-2015
Laboratoire de Microbiologie Fondamentale et Pathogénicité
2008
Charité - Universitätsmedizin Berlin
2007
A gene for autosomal recessive parkinsonism, PARK2 (parkin), has recently been identified on chromosome 6q and shown to be mutated in Japanese European families, mostly with early-onset parkinsonism. Here we present a large pedigree from South Tyrol (a region of northern Italy) adult-onset, clinically typical tremor-dominant parkinsonism apparently dominant inheritance. Haplotype analysis excluded linkage the 2p, 4p, 4q regions that harbor genes associated but implicated parkin locus 6q....
Background Three different cell types constitute the glomerular filter: mesangial cells, endothelial and podocytes. However, to what extent cellular heterogeneity exists within healthy populations remains unknown. Methods We used nanodroplet-based highly parallel transcriptional profiling characterize content of purified wild-type mouse glomeruli. Results Unsupervised clustering nearly 13,000 single-cell transcriptomes identified three known types. provide a comprehensive online atlas gene...
The transcription factor Wilms' tumor suppressor 1 (WT1) is key to podocyte development and viability; however, WT1 transcriptional networks in podocytes remain elusive. We provide a comprehensive analysis of the genome-wide network vivo using chromatin immunoprecipitation followed by sequencing (ChIPseq) RNA techniques. Our data show specific role for regulating podocyte-specific transcriptome through binding both promoters enhancers target genes. Furthermore, we inferred consisting WT1,...
<b><i><i>Background:</i></i></b> Early onset PD has been associated with different mutations in the <i>Parkin</i> gene, including exon deletions and duplications. <b><i><i>Methods:</i></i></b> The authors performed an extensive mutational analysis on 50 probands of at younger than years age. Thirteen were ascertained from a registry familial 37 by age years, blind to family history. Mutational was undertaken available members included conventional techniques (single strand conformation...
Abstract Early‐onset parkinsonism is frequently reported in connection with mutations the parkin gene. In this study, we present results of extensive genetic screening for 111 community‐derived early‐onset patients (age onset <50 years) from Germany an overall mutation rate 9.0%. Gene dosage alterations represented 67% found, underlining importance quantitative analyses . summary, accounted a low but significant percentage sample.
Mechanosensitive activation of YAP is an early response in damaged kidneys.
Abstract Mitochondrial dysfunction and alterations in energy metabolism have been implicated a variety of human diseases. fusion is essential for maintenance mitochondrial function requires the prohibitin ring complex subunit prohibitin‐2 (PHB2) at inner membrane. Here, we provide link between PHB2 deficiency hyperactive insulin/IGF‐1 signaling. Deletion podocytes mice, terminally differentiated cells kidney filtration barrier, caused progressive proteinuria, failure, death animals resulted...
Development of the metanephric kidney depends on tightly regulated interplay between self-renewal and differentiation a nephron progenitor cell (NPC) pool. Several key factors required for survival NPCs have been identified, including fibroblast growth factor (FGF) signaling transcription Wilms' tumor suppressor 1 (WT1). Here, we present evidence that WT1 modulates FGF by activating expression arrest-specific (Gas1), novel target gene modulator signaling. We show directly binds to conserved...
Regulated intracellular proteostasis, controlled in part by proteolysis, is essential maintaining the integrity of podocytes and glomerular filtration barrier kidney. We applied a novel proteomics technology that enables proteome-wide identification, mapping, quantification protein N-termini to comprehensively characterize cleaved podocyte proteins glomerulus vivo . found evidence defined proteolytic cleavage results various proteoforms important proteins, including those podocin, nephrin,...
Abstract Background Living kidney donors are screened pre-donation to estimate the risk of end-stage disease (ESKD). We evaluate Machine Learning (ML) predict progression function deterioration over time using estimated GFR (eGFR) slope as target variable. Methods included 238 living who underwent donor nephrectomy. divided dataset based on eGFR in third follow-up year, resulting 185 with an average and 53 accelerated declining eGFR-slope . trained three Learning-models (Random Forest [RF],...
Abstract The tumor suppressor p53 is mainly involved in the transcriptional regulation of a large number growth-arrest- and apoptosis-related genes. However, clear understanding which factor/s influences choice between these two opposing p53-dependent outcomes remains largely elusive. We have previously described that response to DNA damage, RNA polymerase II-binding protein Che-1/AATF transcriptionally activates p53. Here, we show Che-1 binds directly This interaction essentially occurs...
The renal filtration barrier is maintained by the podocyte, an epithelial postmitotic cell. Immortalized mouse podocyte cell lines—both in differentiated and undifferentiated state—are widely utilized tools to estimate injury cytoskeletal rearrangement processes vitro. Here, we mapped cultured proteome at a depth of more than 8,800 proteins quantified 7,240 proteins. Copy numbers mutated forms hereditary nephrotic syndrome or focal segmental glomerulosclerosis (FSGS) were assessed. We found...
Degenerative diseases are marked by the progressive accumulation of cellular damage, leading to impaired function and tissue degeneration. Despite advances in single-cell technologies, capturing gradual decline individual cells vivo remains challenging. Here, we present a novel, universal, cross-model framework for quantifying damage at resolution, uncover conserved molecular trajectories This method uses RNA sequencing data enables detection within distinct cell populations under...
Kidney function depends on the filtration of enormous volumes plasma, exposing barrier to mechanical forces. Podocytes must adapt these forces for lifetime an organism as they cannot self-renew. The molecular mechanisms podocyte adaptation stress remain unclear. YAP and TAZ are key mechanotransducers that relay stimuli control transcription. We made use podocyte-specific knockout mouse models Yap (YAPpKO), Taz (TAZpKO), or both (YAPpKO/ TAZpKO) analyzed single-nucleus RNA sequencing...
DNA repair is essential for preserving genome integrity. Podocytes, post-mitotic epithelial cells of the kidney filtration unit, bear limited regenerative capacity, yet their survival indispensable health. Podocyte loss a hallmark aging process and many diseases, but underlying factors remain unclear. We investigated consequences damage in podocyte-specific knockout mouse model Ercc1 cultured podocytes under genomic stress. Furthermore, we characterized damage-related alterations human renal...
Abstract Background Cytomegalovirus (CMV) infections are a common complication after kidney transplantation (KTx) and negatively affecting patient outcome. Valganciclovir (VGC) prophylaxis is often limited by drug‐induced side effects dose reduction due to decline in function. Method In the present study, episodes of CMV viremia first year KTx cohort 316 recipients were analyzed retrospectively identify risk factors linked persistent infections. Results studied cohort, 18.7% patients showed...
Background: The DNA‐binding transcription factor Wilms' Tumor Suppressor‐1 (WT1) plays an essential role in nephron progenitor differentiation during renal development. We previously used Wt1 chromatin‐immunoprecipitation coupled to microarray (ChIP‐chip) identify novel target genes that may regulate nephrogenesis vivo . discovered all three members of the SoxC subfamily, namely, Sox4, Sox11 , and Sox12 are bound by mouse embryonic kidneys play master roles determining neuronal mesenchymal...