A5011392585- Chronic Kidney Disease and Diabetes
- Single-cell and spatial transcriptomics
- Dialysis and Renal Disease Management
- Renal and related cancers
- Renin-Angiotensin System Studies
- Renal Diseases and Glomerulopathies
- Inorganic Fluorides and Related Compounds
- Birth, Development, and Health
- Chronic Lymphocytic Leukemia Research
- Mast cells and histamine
- Health, Environment, Cognitive Aging
- Pancreatitis Pathology and Treatment
- Endoplasmic Reticulum Stress and Disease
- Renal Transplantation Outcomes and Treatments
- Epigenetics and DNA Methylation
- Lymphoma Diagnosis and Treatment
- Vitamin C and Antioxidants Research
- Organ Donation and Transplantation
- Receptor Mechanisms and Signaling
- Phagocytosis and Immune Regulation
- Gene Regulatory Network Analysis
- Renal and Vascular Pathologies
- Organ Transplantation Techniques and Outcomes
- Helicobacter pylori-related gastroenterology studies
- Ethics in medical practice
University of Pennsylvania
2020-2024
Charité - Universitätsmedizin Berlin
2023-2024
Berlin Institute of Health at Charité - Universitätsmedizin Berlin
2023-2024
Medizinische Hochschule Hannover
2013-2024
California University of Pennsylvania
2022
Friedrich-Alexander-Universität Erlangen-Nürnberg
2013
University of Zurich
1990
Abstract Determining the epigenetic program that generates unique cell types in kidney is critical for understanding cell-type heterogeneity during tissue homeostasis and injury response. Here, we profile open chromatin gene expression developing adult mouse kidneys at single resolution. We show reliance of on distal regulatory elements (enhancers). reveal key type-specific transcription factors major gene-regulatory circuits cells. Dynamic changes nephron progenitor differentiation...
The kidney has tremendous capacity to repair after acute injury, however, pathways guiding adaptive and fibrotic are poorly understood. We developed a model of regeneration by titrating ischemic injury dose. performed detailed biochemical histological analysis profiled transcriptomic changes at bulk single-cell level (> 110,000 cells) over time. Our highlights proximal tubule cells as key susceptible injury. Adaptive correlated with fatty acid oxidation oxidative phosphorylation. identify...
Microscopic analysis of urine sediment is probably the most commonly used diagnostic procedure in nephrology. The urinary cells, however, have not yet undergone careful unbiased characterization.
The cardioprotective and anti-inflammatory effects of long chain omega-3 polyunsaturated fatty acids (n3 PUFA) are believed to be partly mediated by their oxygenated metabolites (oxylipins). In the last two decades interest in a novel group autacoids termed specialized pro-resolving mediators (SPMs) increased. These actively involved resolution inflammation. SPMs multiple hydroxylated including resolvins, maresins, protectins derived from n3 PUFA eicosapentaenoic acid (EPA) docosahexaenoic...
Abstract Kidneys possess one of the most intricate three-dimensional cellular structures in body, yet spatial and molecular principles kidney health disease remain inadequately understood. Here, we have generated high-quality datasets for 81 samples, including single cell (sc), nuclear (sn), spot level (Visium) resolution (CosMx) (sp)-RNA expression, sn open chromatin, capturing cells from healthy, diabetic, hypertensive diseased human kidneys. By combining snRNA, snATAC scRNA sequencing...
Abstract Adiponectin is a secretory protein, primarily produced in adipocytes. However, low but detectable expression of adiponectin can be observed cell types beyond adipocytes, particularly kidney tubular cells, its local renal role unknown. We assessed the impact by utilizing male inducible cell-specific overexpression or knockout mice. Kidney-specific induces doubling phosphoenolpyruvate carboxylase and enhanced pyruvate-mediated glucose production, tricarboxylic acid cycle intermediates...
Diabetic kidney disease (DKD) is the most common cause of renal failure. Therapeutics development hampered by our incomplete understanding animal models on a cellular level. We show that ZSF1 rats recapitulate human DKD phenotypic and transcriptomic Tensor decomposition prioritizes proximal tubule (PT) stroma as phenotype-relevant cell types exhibiting continuous lineage relationship. As features endothelial dysfunction, oxidative stress, nitric oxide depletion, soluble guanylate cyclase...
Mouse models have been widely used to understand kidney disease pathomechanisms and play an important role in drug discovery. However, these not systematically analyzed compared. The authors characterized 18 different mouse at both bulk single-cell gene expression levels compared data from diabetic (DKD) mice patients with DKD. Although single cell-level changes were mostly model-specific, showed similar when a pathway level. also found that fractions of cell types are major drivers...
Mineralocorticoid excess commonly leads to hypertension and kidney disease. In our study, we employed single-cell expression chromatin accessibility tools characterize the mineralocorticoid target genes cell types. We demonstrated that effects are established through open gene expression, primarily in principal connecting tubule cells, a lesser extent, segments of distal convoluted cells. examined kidney-protective steroidal non-steroidal antagonists (MRAs), as well amiloride, an epithelial...
Peritoneal dialysis (PD) is limited by glucose-mediated peritoneal membrane (PM) fibrosis, angiogenesis, and ultrafiltration failure. Influencing PM integrity pharmacologically targeting sodium-dependent glucose transporter (SGLT)-mediated uptake has not been studied. In this study, wildtype C57Bl/6N mice were treated with high-glucose dialysate via an intraperitoneal catheter, or without addition of selective SGLT2 inhibitor dapagliflozin. structural changes, capacity, equilibration testing...
Purpose Women on dialysis rarely become pregnant. However, the overall rate of successful pregnancies is increasing in this patient population and breastfeeding becomes an option for mothers dialysis. In study we performed a systematic breast milk composition analysis mother chronic hemodialysis (HD). Methods Specimens blood were collected regular intervals before after HD from 39-year old woman starting day 10 postpartum. Samples analyzed electrolytes, retention solutes, nutrients other...
Dialysis patients are at increased risk of HF. However, diagnostic utility NT-proBNP as a biomarker is decreased in on dialysis. GDF-15 and cNEP biomarkers distinct mechanisms that may contribute to HF pathophysiology such cohorts. The aim this study was determine whether growth differentiation factor-15 (GDF-15) circulating neprilysin (cNEP) improve the diagnosis congestive heart failure (HF) dialysis.We compared concentrations NT-proBNP, GDF-15, along with activity chronic dialysis without...
Peritoneal membrane (PM) damage during peritoneal dialysis (PD) is mediated largely by high glucose (HG)-induced pro-inflammatory and neo-angiogenic processes, resulting in PM fibrosis ultrafiltration failure. We recently demonstrated a crucial role for protein kinase C (PKC) isoform α mesothelial cells.In this study we investigate the of PKCβ vitro using primary mouse macrophages (MPMΦ), human (HMΦ) immortalized cells (MPMCs), as well vivo chronic PD model.We demonstrate that predominant...
Peritoneal dialysis (PD) employs hypertonic glucose to remove excess water and uremic waste. membrane failure limits its long-term use. T-cell cytokines promote this decline. differentiation is critically determined by the microenvironment. We here study how PD-range regulates polarization IL-17 production. In human peritoneal cavity, CD3+ cell numbers increased in PD. Single RNA sequencing detected expression of T helper (Th) 17 signature genes RORC IL23R. vitro, stimulated spontaneous...