A5002572018- Metabolism and Genetic Disorders
- Eicosanoids and Hypertension Pharmacology
- Peroxisome Proliferator-Activated Receptors
- Acute Kidney Injury Research
- Diet and metabolism studies
- Cellular Mechanics and Interactions
- Cancer, Hypoxia, and Metabolism
- Renal and related cancers
- Chronic Kidney Disease and Diabetes
- Microtubule and mitosis dynamics
- DNA Repair Mechanisms
- Biochemical Acid Research Studies
- Pluripotent Stem Cells Research
- Dialysis and Renal Disease Management
- Advanced Glycation End Products research
- 3D Printing in Biomedical Research
- Genomics and Chromatin Dynamics
- Cancer Genomics and Diagnostics
- Fibroblast Growth Factor Research
- Alcohol Consumption and Health Effects
- Bladder and Urothelial Cancer Treatments
- Adipose Tissue and Metabolism
- Silk-based biomaterials and applications
- MicroRNA in disease regulation
- Metabolomics and Mass Spectrometry Studies
University of Pittsburgh
2021-2025
Children's Hospital of Pittsburgh
2022-2023
University of Pittsburgh Medical Center
2023
UPMC Health System
2023
University of Virginia
2015-2021
Vascularization plays a critical role in organ maturation and cell type development. Drug discovery, mimicry, ultimately transplantation hinge on achieving robust vascularization of vitro engineered organs. Here, focusing human kidney organoids, we overcame this hurdle by combining induced pluripotent stem (iPSC) line containing an inducible ETS translocation variant 2 (ETV2) (a transcription factor playing endothelial development) that directs differentiation vitro, with non-transgenic iPSC...
Dicarboxylic fatty acids are generated in the liver and kidney a minor pathway called acid ω-oxidation. The effects of consuming dicarboxylic as an alternative source dietary fat have not been explored. Here, we fed dodecanedioic acid, 12-carbon (DC12), to mice at 20% daily caloric intake for nine weeks. DC12 increased metabolic rate, reduced body fat, improved glucose tolerance. We observed DC12-specific breakdown products liver, kidney, muscle, heart, brain, indicating that oral escaped...
The renal tubular epithelial cells (RTECs) are particularly vulnerable to acute kidney injury (AKI). While fatty acids the preferred energy source for RTECs via acid oxidation (FAO), FAO-mediated H2O2 production in mitochondria has been shown be a major of oxidative stress. We have previously that mitochondrial flavoprotein, long-chain acyl-CoA dehydrogenase (LCAD), which catalyzes key step FAO, directly produces vitro. Further, we showed LCAD becomes hyposuccinylated during AKI. Here,...
Vertebrate embryos undergo dramatic shape changes at gastrulation that require locally produced and anisotropically applied forces, yet how these forces are transmitted across tissues remains unclear. We show depletion of myosin regulatory light chain (RLC) levels in the embryo blocks force generation through two distinct mechanisms: destabilizing II (MII) hexameric complex inhibiting MII contractility. Molecular dissection mechanisms demonstrates normal convergence requires contractility we...
Although aneuploidy is found in the majority of tumors, degree varies widely. It unclear how cancer cells become aneuploid or highly tumors are different from those more normal ploidy. We developed a simple computational method that measures structural rearrangements large chromosome regions 522 human breast The Cancer Genome Atlas (TCGA). Highly overexpress activators mitotic transcription and genes encoding proteins segregate chromosomes. Overexpression three transcriptional regulators,...
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,...
Significance Statement In this study, we demonstrate that a common, low-cost compound known as octanedioic acid (DC 8 ) can protect mice from kidney damage typically caused by ischemia-reperfusion injury or the chemotherapy drug cisplatin. This seems to enhance peroxisomal activity, which is responsible for breaking down fats, without adversely affecting mitochondrial function. DC not only affordable and easy administer but also effective. These encouraging findings suggest could potentially...
Abstract Acute kidney injury (AKI) manifests as a major health concern, particularly for the elderly. Understanding AKI‐related proteome changes is critical prevention and development of novel therapeutics to recover function mitigate susceptibility recurrent AKI or chronic disease. In this study, mouse kidneys were subjected ischemia‐reperfusion injury, contralateral remained uninjured enable comparison assess injury‐induced in proteome. A ZenoTOF 7600 mass spectrometer was optimized...
Succinylation is an understudied posttranslational modification that has been shown to increase peroxisomal activity. Furthermore, increased activity reduce oxidative stress and protect proximal tubules after acute kidney injury. Analysis of mass spectrometry succinylomic proteomic data reveals a novel role for Parkinson’s related Park7 in mediating Nrf2 antioxidant response This protection pathway provides new insights injury prevention development therapeutics.
Kif2a is a member of the kinesin-13 microtubule depolymerases, which tightly regulate dynamics for many cellular processes. We characterized depletion in Xenopus animal caps and embryos. generates defects blastopore closure. These are rescued by removing cap, suggesting that Kif2a-depleted not compliant enough to allow gastrulation movements. Gastrulation mutated an Aurora kinase phosphorylation site, phenotypes caused problems mitosis. During cap mitoses, localizes spindle poles...
Acute kidney injury (AKI) manifests as a major health concern, particularly for the elderly. Understanding AKI-related proteome changes is critical prevention and development of novel therapeutics to recover function mitigate susceptibility recurrent AKI or chronic disease. In this study, mouse kidneys were subjected ischemia-reperfusion injury, contralateral remained uninjured enable comparison assess injury-induced in proteome. A fast-acquisition rate ZenoTOF 7600 mass spectrometer was...
Abstract Vascularization plays a critical role in organ maturation and cell type development. Drug discovery, mimicry, ultimately transplantation clinical setting thereby hinges on achieving robust vascularization of vitro engineered organs. Here, focusing human kidney organoids, we overcome this hurdle by combining an inducible ETS translocation variant 2 ( ETV2 ) induced pluripotent stem (iPSC) line, which directs endothelial fate, with non-transgenic iPSC line suspension organoid culture....
ABSTRACT Proximal tubular epithelial cells (PTECs) are particularly vulnerable to acute kidney injury (AKI). While fatty acids the preferred energy source for PTECs via acid oxidation (FAO), FAO-mediated H 2 O production in mitochondria has been shown be a major of oxidative stress. We have previously that mitochondrial flavoprotein, long-chain acyl-CoA dehydrogenase (LCAD), which catalyzes key step FAO, directly produces vitro . Further we established loss lysine deacylase, Sirtuin 5 (...
Mice with inducible urothelial deletion of fibroblast growth factor receptor 2 (ShhCreERT2;Fgfr2
Introduction Lysine succinylation is a post-translational modification associated with the control of several diseases, including acute kidney injury (AKI). It suggested that hypersuccinylation favors peroxisomal fatty acid oxidation (FAO) instead mitochondrial. In addition, medium-chain acids (MCFAs) dodecanedioic (DC 12 ) and octanedioic 8 ), upon FAO, generate succinyl-CoA, resulting in hypersuccinylation. DC convenient, inexpensive, easily administered, efficient. We believe this study...
Vascularization plays a critical role in organ maturation and cell type development. Drug discovery, mimicry, transplantation hinge on achieving robust vascularization of vitro engineered organs. Here, focusing human kidney organoids, we overcome this hurdle by combining an inducible ETS translocation variant 2 (ETV2) induced pluripotent stem (iPSC) line, which directs endothelial fate, with non-transgenic iPSC line suspension culture. The resulting organoids show extensive cells, more...
Abstract Aurora kinase B (AURKB in human, Ipl1 S. cerevisiae ) is a master regulator of mitosis and its dysregulation has been implicated chromosome instability. AURKB accumulates the nucleus S-phase regulated by CHK1 but not DNA Damage Response (DDR). Here we show that conserved role to recover from replication stress restart forks. Active localized forks after prolonged arrest. phosphorylation induces activating PLK1 both Plk1 are required deactivate DDR. Clinical trials with inhibitors...