A5073284613- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- Genetic and Kidney Cyst Diseases
- Immune Cell Function and Interaction
- Complement system in diseases
- Single-cell and spatial transcriptomics
- Nitric Oxide and Endothelin Effects
- Chronic Disease Management Strategies
- Reproductive System and Pregnancy
- Mitochondrial Function and Pathology
- Ion Transport and Channel Regulation
- Caveolin-1 and cellular processes
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Immune cells in cancer
- T-cell and B-cell Immunology
- Phagocytosis and Immune Regulation
- Mathematical Biology Tumor Growth
- Intensive Care Unit Cognitive Disorders
- Chemical Reactions and Isotopes
- Antiplatelet Therapy and Cardiovascular Diseases
- Hematological disorders and diagnostics
- Inflammasome and immune disorders
- Sarcoma Diagnosis and Treatment
- Metabolism and Genetic Disorders
- Systemic Lupus Erythematosus Research
University Hospital Cologne
2020-2024
University of Cologne
2012-2024
Cologne Excellence Cluster on Cellular Stress Responses in Aging Associated Diseases
2020
Washington University in St. Louis
2016-2017
Philipps University of Marburg
2009-2010
Vollum Institute
2009
University of Lübeck
2009
Oregon Health & Science University
2009
Albert Einstein College of Medicine
2009
University of California, Davis
2009
It has been proposed that activation of endothelial SK3 (K(Ca)2.3) and IK1 (K(Ca)3.1) K+ channels plays a role in the arteriolar dilation attributed to an endothelium-derived hyperpolarizing factor (EDHF). However, our understanding precise function EDHF dilator response blood pressure control remains incomplete. To clarify roles their contribution vivo, we generated mice deficient for both channels.Expression IK1(-/-)/SK3(T/T) was characterized by patch-clamp, membrane potential...
Acquired thrombotic thrombocytopenic purpura (aTTP) is a rare but life-threatening condition. In 2018, the nanobody caplacizumab was approved for treatment of adults experiencing an acute episode aTTP, in conjunction with plasma exchange (PEX) and immunosuppression minimum 30 days after stopping daily PEX. We performed retrospective, observational analysis on use 60 patients from 29 medical centers Germany during disease management. Caplacizumab led to rapid normalization platelet count...
Dendritic cells (DCs) are thought to form a dendritic network across barrier surfaces and throughout organs, including the kidney, perform an important sentinel function. However, previous studies of DC function used markers, such as CD11c or CX3CR1, that not unique DCs. Here, we evaluated role DCs in renal inflammation using reporter mouse line two lines with DC-specific reporters,
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...
Abstract Introduction of the nanobody caplacizumab was shown to be effective in treatment acquired thrombotic thrombocytopenic purpura (aTTP) acute setting. The official recommendations include plasma exchange (PEX), immunosuppression, and use for a minimum 30 days after stopping daily PEX. This study retrospective, observational analysis 60 patients from 29 medical centers Germany. Immunosuppressive led rapid normalization ADAMTS13 activities (calculated median, 21 days). In 35 patients,...
Inflammation conveys the development of glomerular injury and is a major cause progressive kidney disease. NF-κB signaling among most important regulators proinflammatory signaling. Its role in podocytes, epithelial cells at filtration barrier, poorly understood. Here, we inhibited podocytes by specific ablation essential modulator (NEMO, IKKγ). Podocyte-specific NEMO-deficient mice (NEMO(pko)) were viable did not show proteinuria or overt changes morphology. After induction...
Focal segmental glomerulosclerosis (FSGS) is a syndrome that involves kidney podocyte dysfunction and causes chronic disease. Multiple factors including chemical toxicity, inflammation, infection underlie FSGS; however, highly penetrant disease genes have been identified in small fraction of patients with family history FSGS. Variants apolipoprotein L1 (APOL1) linked to FSGS African Americans HIV or hypertension, supporting the proposal genetic enhance susceptibility. Here, we used...
In glomerular disease, podocyte injury results in a dramatic change cell morphology known as foot process effacement. Remodeling of the actin cytoskeleton through activity small GTPases was identified key mechanism effacement, with increased membrane and motility vitro . However, whether podocytes are stationary or actively moving cells vivo remains debated. Using intravital kidney slice two–photon imaging three-dimensional structure mouse podocytes, we found that uninjured remained...
Three-dimensional imaging has advanced basic research and clinical medicine. However, limited resolution imperfections of real-world 3D image material often preclude algorithmic analysis. Here, we present a methodological framework for such analysis functional spatial relations in experimental nephritis. First, optical tissue clearing protocols were optimized to preserve fluorescence signals light-sheet-fluorescence-microscopy compensated attenuation effects using adjustable correction...
Abstract Chronic alterations in calcium (Ca 2+ ) signalling podocytes have been shown to cause proteinuria and progressive glomerular diseases. However, it is unclear whether short Ca peaks influence biology podocyte injury. Here we generated a DREADD (Designer Receptor Exclusively Activated by Designer Drug) knock-in mouse line manipulate intracellular levels. By mating podocyte-specific Cre driver are able investigate the impact of on living animals. Activation engineered G-protein coupled...
Significance Statement Podocin R229Q results from the most frequent missense variant in NPHS2 , and its association with FSGS when podocin is transassociated a second mutation well recognized. However, because observational studies are ambiguous appropriate animal lacking, isolated pathogenic potency not entirely clear. In this study, authors introduced genetic alteration mice assessed phenotype using super-resolution microscopy albuminuria measurements. They demonstrated deleterious effect...
Maintenance of the glomerular filtration barrier with its fenestrated endothelium, basement membrane, and podocytes as outer layer, is a major prerequisite for proper renal function. Tight regulation balance between plasticity rigidity podocytes' architecture required to prevent onset disease, mainly proteinuria. The underlying cellular signaling pathways that regulate organization cytoskeleton are still matter controversial debate. In this study, we investigated role NF-κB pathway in...
Podocytes form the kidney filtration barrier and continuously adjust to external stimuli preserve their integrity even in presence of inflammation. It was suggested that canonical toll-like receptor signaling, mediated by adaptor protein MYD88, plays a crucial role initiating inflammatory responses glomerulonephritis (GN). We explored influence podocyte-intrinsic MYD88 challenging wild-type (WT) podocyte-specific Myd88 knockout (MyD88pko) mice, with model experimental GN (nephrotoxic...
Significance Statement Treatment of acute, crescentic glomerulonephritis (GN) consists unspecific and potentially toxic immunosuppression. T cells are central in the pathogenesis GN, various checkpoint molecules control their activation. The immune molecule B T-lymphocyte attenuator (BTLA) has shown potential for restraining inflammation other T-cell–mediated disease models. To investigate its role GN a murine model nephritis, authors induced nephrotoxic nephritis BTLA-deficient mice...
Cyclin-dependent kinase 5 (Cdk5) is expressed in terminally differentiated cells, where it drives development, morphogenesis, and survival. Temporal spatial activity regulated by specific activators of Cdk5, dependent on the cell type environmental factors. In kidney, Cdk5 exclusively glomerular epithelial cells called podocytes. disease, signaling mechanisms via have been addressed single or combined conventional knockout known Cdk5. A protective, anti-apoptotic role has ascribed to but not...
Isolated myeloid sarcoma is a rare presentation of acute leukemia. There are limited data available concerning the prognostic relevance and right treatment strategy for this clinical scenario. Here, we report case leukemia with extensive lesions fractures in multiple bones 64-yr-old male patient. Remarkably, high-dose cytarabine regimen led to rapid remineralization all bone recovery patient's mobility within few weeks. Thereby, surgical radiotherapy could be avoided, supporting role...
Abstract Background Multimorbid and frail elderly patients often carry a high burden of treatment. Hospitalization due to the onset an acute illness can disrupt fragile balance, resulting in further readmissions after hospital discharge. Current models care Germany do not meet needs this patient group. Rather lack coordination integration combined with interdisciplinary approaches result fragmented inadequate increase treatment even more. Methods eliPfad is randomized controlled trial...
Abstract • Background: Multimorbid and frail elderly patients often carry a high burden of treatment. Hospitalization due to the onset an acute illness can disrupt fragile balance, resulting in further readmissions after hospital discharge. Current models care Germany do not meet needs this patient group. Rather lack coordination integration combined with interdisciplinary approaches result fragmented inadequate increase treatment even more. Methods: eliPfad is randomized controlled trial...