A5014937991- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- Renal and related cancers
- Genetic and Kidney Cyst Diseases
- Wnt/β-catenin signaling in development and cancer
- Systemic Sclerosis and Related Diseases
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Pancreatic function and diabetes
- Ion Transport and Channel Regulation
- Melanoma and MAPK Pathways
- Autoimmune Bullous Skin Diseases
- Cell Adhesion Molecules Research
- Erythrocyte Function and Pathophysiology
- Protein Kinase Regulation and GTPase Signaling
- Platelet Disorders and Treatments
- Renal cell carcinoma treatment
- Signaling Pathways in Disease
- Nerve injury and regeneration
- Tuberous Sclerosis Complex Research
- Biomedical Research and Pathophysiology
- Genetic Syndromes and Imprinting
- Caveolin-1 and cellular processes
- Renal and Vascular Pathologies
- Vasculitis and related conditions
- Proteoglycans and glycosaminoglycans research
Children's Hospital Colorado
2024
University of Colorado Denver
2024
University of Pennsylvania
2015-2024
Penn Center for AIDS Research
2018-2024
University of Pennsylvania Health System
2018-2024
The Bronx Defenders
2023
Albert Einstein College of Medicine
2023
Children's Hospital at Montefiore
2023
University of Michigan–Ann Arbor
2002-2022
Johns Hopkins University
2022
Glomerular injury and proteinuria in diabetes (types 1 2) IgA nephropathy is related to the degree of podocyte depletion humans. For determining causal relationship between glomerulosclerosis, a transgenic rat strain which human diphtheria toxin receptor specifically expressed podocytes was developed. The rodent homologue does not act as (DT) receptor, thereby making rodents resistant DT. Injection DT into rats but wild-type resulted dose-dependent from glomeruli. Three stages glomerular...
NPHS2 was recently identified as a gene whose mutations cause autosomal recessive steroid-resistant nephrotic syndrome. Its product, podocin, is new member of the stomatin family, which consists hairpin-like integral membrane proteins with intracellular NH2- and COOH-termini. Podocin expressed in glomerular podocytes, but its subcellular distribution interaction other are unknown. Here we show, by immunoelectron microscopy, that podocin localizes to podocyte foot process membrane, at...
Diabetic nephropathy (DN) is among the most lethal complications that occur in type 1 and 2 diabetics. Podocyte dysfunction postulated to be a critical event associated with proteinuria glomerulosclerosis glomerular diseases including DN. However, molecular mechanisms of podocyte development DN are not well understood. Here we have shown activity mTOR complex (mTORC1), kinase senses nutrient availability, was enhanced podocytes diabetic animals. Further, podocyte-specific mTORC1 activation...
NPHS2 was recently identified as a gene whose mutations cause autosomal recessive steroid-resistant nephrotic syndrome. Its product, podocin, is new member of the stomatin family, which consists hairpin-like integral membrane proteins with intracellular NH2- and COOH-termini. Podocin expressed in glomerular podocytes, but its subcellular distribution interaction other are unknown. Here we show, by immunoelectron microscopy, that podocin localizes to podocyte foot process membrane, at...
Podocyte dysfunction, one of the major causes proteinuria, leads to glomerulosclerosis and end stage renal disease, but its underlying mechanism remains poorly understood. Here we show that Wnt/beta-catenin signaling plays a critical role in podocyte injury proteinuria. Treatment with adriamycin induced Wnt activated beta-catenin mouse podocytes. Overexpression Wnt1 vivo glomerular aggravated albuminuria adriamycin-induced suppression nephrin expression, whereas blockade Dickkopf-1...
Cytokines such as tumor necrosis factor alpha (TNF) profoundly affect endothelial cell function, promoting for example interaction with leukocytes and inducing a procoagulant phenotype. Changes of this nature are likely to be central the proinflammatory effects TNF. In order elucidate molecular mechanisms by which TNF alters function we utilized differential plaque hybridization identify TNF-responsive genes. Forty TNF-inducible cDNAs were identified on cross-hybridization found arise from...
Dicer is an enzyme that generates microRNA (miRNA), which are small, noncoding RNA function as important regulators of gene and protein expression. For exploration the functional roles miRNA in glomerular biology, was inactivated selectively mouse podocytes. Mutant mice developed proteinuria 4 to 5 weeks after birth died several later, presumably from kidney failure. Multiple abnormalities were observed glomeruli mutant mice, including foot process effacement, irregular split areas basement...
A properly established and maintained podocyte intercellular junction, or slit diaphragm, is a necessary component of the selective permeability barrier kidney glomerulus. The observation that mutation deletion diaphragm transmembrane protein nephrin results in failure foot process morphogenesis concomitant proteinuria first suggested hypothesis serves as signaling complex directly integrates junctional integrity with cytoskeletal dynamics. observations made herein provide direct evidence to...
The application of deep learning for automated segmentation (delineation boundaries) histologic primitives (structures) from whole slide images can facilitate the establishment novel protocols kidney biopsy assessment. Here, we developed and validated networks structures on biopsies nephrectomies. For development, examined 125 Minimal Change Disease collected across 29 NEPTUNE enrolling centers along with 459 stained Hematoxylin & Eosin (125), Periodic Acid Schiff Silver (102), Trichrome...
Abstract Summary: We report a transgenic mouse line that expresses Cre recombinase exclusively in podocytes. Twenty‐ four founders were generated which was placed under the regulation of 2.5‐kb fragment human NPHS2 promoter. Previously, this shown to drive beta‐galactosidase (β‐gal) expression podocytes mice. For analysis, founder mice bred with ROSA26 mice, reporter β‐gal cells undergo recombination. Eight 24 lines found express kidney. Histological analysis kidneys showed confined...
Signal transducers and activators of transcription (STATs) are factors that mediate normal biologic responses to cytokines growth factors. However, abnormal activation certain STAT family members, including Stat3, is increasingly associated with oncogenesis. In fibroblasts expressing the Src oncoprotein, Stat3 induces specific gene expression required for cell transformation. Although tyrosine kinase constitutive phosphorylation on tyrosine, Stat3-mediated regulation requires both serine...
Recent investigations have focused on characterizing the molecular components of podocyte intercellular junction, because several these components, including Nephrin, are functionally necessary for development normal structure and filter integrity. Accumulating evidence suggests that Nephrin-associated protein complex is a signaling nexus. As such, Nephrin-dependent might be mediated in part through Nephrin phosphorylation. Described biochemical mouse genetics experiments demonstrating...
Glomerular visceral epithelial cells (podocytes) appear to play a central role in maintaining the selective filtration barrier of renal glomerulus. While immunoglobulin superfamily member Nephrin was proposed act as cell adhesion molecule at podocyte intercellular junction necessary for glomerular perm selectivity, ligand has not been identified. The existence new subfamily Nephrin-like molecules including Neph1 recently described. Genetic deletion or resulted similar phenotypes foot process...
ABSTRACT. Cellular crescents are a defining histologic finding in many forms of inflammatory glomerulonephritis. Despite numerous studies, the origin glomerular remains unresolved. A genetic cell lineage-mapping study with novel transgenic mouse model was performed to investigate whether visceral epithelial cells, termed podocytes, precursors cells that populate cellular crescents. The podocyte-specific 2.5P-Cre line crossed ROSA26 reporter line, resulting irreversible constitutive...
Diabetic kidney disease (DKD) is the single most common cause of albuminuria and end-stage in United States. We found increased expression Wnt/β-catenin (Ctnnb1) pathway transcripts proteins glomeruli podocytes patients mouse models DKD. Mice with podocyte-specific stabilized Ctnnb1 exhibited basement membrane abnormalities, albuminuria, susceptibility to glomerular injury. deletion or canonical Wnt inhibitor Dickkopf-related protein 1 (Dkk1) also showed Podocytes were less motile adhesive...