A5043034849- Renal and related cancers
- Metabolism and Genetic Disorders
- MicroRNA in disease regulation
- Genetic and Kidney Cyst Diseases
- Pregnancy and preeclampsia studies
- Mitochondrial Function and Pathology
- Renal cell carcinoma treatment
- Diet and metabolism studies
- Amino Acid Enzymes and Metabolism
- Renal Diseases and Glomerulopathies
- Metabolomics and Mass Spectrometry Studies
- Congenital Anomalies and Fetal Surgery
- Chronic Kidney Disease and Diabetes
- Lysosomal Storage Disorders Research
- Adipose Tissue and Metabolism
- Cancer-related molecular mechanisms research
- Pediatric Urology and Nephrology Studies
- Peroxisome Proliferator-Activated Receptors
- Biomedical Research and Pathophysiology
- Systemic Sclerosis and Related Diseases
- RNA modifications and cancer
- PARP inhibition in cancer therapy
- Glycosylation and Glycoproteins Research
- Acute Kidney Injury Research
- Bone and Joint Diseases
University of Pittsburgh
2014-2024
Children's Hospital of Pittsburgh
2014-2024
Icahn School of Medicine at Mount Sinai
2022-2024
University of Pittsburgh Medical Center
2017-2022
The University of Queensland
2012-2016
MicroRNAs are small noncoding RNAs that post-transcriptionally regulate mRNA levels. While previous studies have demonstrated miRNAs indispensable in the nephron progenitor and ureteric bud lineage, little is understood about stromal during kidney development. The renal stroma (marked by expression of FoxD1) gives rise to interstitium, a subset peritubular capillaries, multiple supportive vascular cell types including pericytes glomerular mesangium. In this study, we generated...
Significance Statement Regulation of endothelial cells is important in many biologic processes, including development, organ function, and disease. The kidney vasculature highly sensitive to hypoxic injury has a limited capacity for repair. AKI as result decreased blood flow common, there are no current therapies. MicroRNAs small noncoding RNAs that inhibit expression target genes. Endothelial-derived miR-17∼92 cluster microRNAs critical function repair during mice. Furthermore,...
To identify therapies for combined D, L-2-hydroxyglutaric aciduria (C-2HGA), a rare genetic disorder caused by recessive variants in the SLC25A1 gene. Patients C-2HGA were identified and diagnosed whole exome sequencing biochemical genetics testing. Patient derived fibroblasts then treated with phenylbutyrate functional effects assessed metabolomics RNA-sequencing. In this study, we demonstrated that patient exhibited impaired cellular bioenergetics. Moreover, Fibroblasts form one worsened...
Crim1 is a transmembrane protein that regulates the bioavailability of growth factors such as VEGFA. Crim1(KST264)(/)(KST264) hypomorphic mice develop renal disease characterized by glomerular cysts and loss endothelial integrity, progressing to peritubular pericystic fibrosis. Peritubular capillary cells display morphological changes well detachment from basement membrane. In this study, gene expression profiling CD31(+) isolated kidneys showed up-regulation transcripts associated with...
The epithelial sodium channel (ENaC) is expressed in the cells of distal convoluted tubules, connecting and cortical collecting duct (CCD) kidney nephron. Under regulation steroid hormone aldosterone, ENaC a major determinant (Na+ ) water balance. ability aldosterone to regulate microRNAs (miRs) has recently been realized, but role miRs Na+ not well established. Here we demonstrate that expression miR cluster mmu-miR-23-24-27, upregulated CCD by stimulation both vitro vivo. Increasing these...
Low nephron endowment at birth has been associated with an increased risk for developing hypertension and chronic kidney disease. We demonstrated in earlier study that conditional deletion of the microRNA (miRNA)-processing enzyme Dicer from progenitors results premature depletion expression proapoptotic protein Bim (also known as Bcl-2L11). In this study, we generated a compound mouse model both Bim, to determine biologic significance Dicer-deficient progenitors. The loss partially restored...
Karyomegalic interstitial nephritis (KIN) is a genetic adult-onset chronic kidney disease (CKD) characterized by genomic instability and mitotic abnormalities in the tubular epithelial cells. KIN caused recessive mutations FAN1 DNA repair enzyme. However, endogenous source of damage FAN1/KIN kidneys has not been identified. Here we show, using FAN1-deficient human renal cells (hRTECs) FAN1-null mice as model KIN, that pathophysiology triggered hypersensitivity to reactive oxygen species...
We have previously demonstrated that loss of miR-17~92 in nephron progenitors a mouse model results renal hypodysplasia and chronic kidney disease. Clinically, decreased congenital endowment because is associated with an increased risk hypertension disease, this at least partly dependent on the self-renewal progenitors. Here, we present evidence for novel molecular mechanism regulating by highly conserved cluster. Whole transcriptome sequencing revealed lacking cluster Cftr expression....
Crim1 hypomorphic (Crim1(KST264/KST264)) mice display progressive renal disease characterized by glomerular defects, leaky peritubular vasculature, and interstitial fibrosis. Here we show that 27% of these also present with hydronephrosis, suggesting obstructive nephropathy. Dynamic magnetic resonance imaging using Magnevist showed fast development hypo-intense signal in the kidneys Crim1(KST264/KST264) mice, pooling filtrate within parenchyma. Rhodamine dextran (10 kDa) clearance was...
Congenital medullary dysplasia with obstructive nephropathy is a common congenital disorder observed in paediatric patients and represents the foremost cause of renal failure. However, molecular processes regulating normal papillary outgrowth during postnatal period are unclear. In this study, transcriptional profiling medulla across development revealed enrichment non-canonical Wnt signalling, vascular development, planar cell polarity genes, all which may contribute to perinatal...
Very long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is an autosomal recessive disease that prevents the body from utilizing fatty acids for energy, most needed during stress and fasting. Symptoms can appear infancy through childhood adolescence or early adulthood, include hypoglycemia, recurrent rhabdomyolysis, myopathy, hepatopathy, cardiomyopathy. REN001 a peroxisome-proliferator-activated receptor delta (PPARδ) agonist modulates expression of genes coding acid β-oxidation enzymes...
The molecular events driving specification of the kidney have been well characterized. However, how initial field size is established, patterned, and proportioned not Lhx1 a transcription factor expressed in pronephric progenitors required for kidney, but few interacting proteins or downstream targets identified. By tandem-affinity purification, we isolated FRY like transcriptional coactivator (Fryl), one two paralogous genes, fryl furry (fry), described vertebrates. Both were found to...
Mammalian nephrons originate from a population of nephron progenitor cells, and changes in these cells' transcriptomes contribute to the cessation nephrogenesis, an important determinant number. To characterize microRNA (miRNA) expression identify putative cis-regulatory regions, we collected cells mouse kidneys at embryonic day 14.5 postnatal zero assayed small RNA transposase-accessible chromatin. We detect 1104 miRNA (114 with changes), 46,374 chromatin accessible regions (2103...
MicroRNAs (miRNAs) are small non-coding RNAs that essential for the regulation of gene expression and play critical roles in human health disease. Here we present comprehensive miRNA profiling data mouse nephrogenic mesenchymal progenitors, a population cells enriched nephron progenitors give rise to most cell-types nephron, functional unit kidney. We describe with 162 miRNAs differentially expressed when compared whole also annotated 49 novel developing kidney experimentally validated 4...
PurposeTo identify therapies for Combined D, L-2-hydroxyglutaric aciduria (C-2HGA), a rare genetic disorder caused by recessive mutations in the SLC25A1 gene.MethodsC-2HGA patients were first identified and diagnosed whole exome sequencing biochemical genetics testing. Patient derived fibroblasts then treated with various therapeutic agents, functional effects assessed metabolomics RNA-sequencing.ResultsIn this study, we demonstrated that C-2HGA patient exhibited impaired cellular...
Abstract Very long chain acyl-CoA dehydrogenase deficiency (VLCADD) is an autosomal recessive disease that prevents the body from utilizing fatty acids for energy, most needed during stress and fasting. Symptoms can appear infancy through childhood adolescence or early adulthood, include hypoglycemia, recurrent rhabdomyolysis, myopathy, hepatopathy, cardiomyopathy. REN001 a peroxisome proliferator activated receptor delta (PPARδ) agonist modulates gene expression of acid β-oxidation enzymes...