A5007066141- Renal and related cancers
- Glaucoma and retinal disorders
- Erythropoietin and Anemia Treatment
- Cancer, Hypoxia, and Metabolism
- Phagocytosis and Immune Regulation
- Immune cells in cancer
- Renal cell carcinoma treatment
- Dialysis and Renal Disease Management
- Ferroptosis and cancer prognosis
- Chronic Kidney Disease and Diabetes
- Ion Transport and Channel Regulation
- Epigenetics and DNA Methylation
- Vitamin D Research Studies
- Urological Disorders and Treatments
- Transplantation: Methods and Outcomes
- Pregnancy and preeclampsia studies
- Immune responses and vaccinations
- Hormonal Regulation and Hypertension
- Birth, Development, and Health
- Retinal Diseases and Treatments
- Liver Disease and Transplantation
- Renal Diseases and Glomerulopathies
- Angiogenesis and VEGF in Cancer
- Renal Transplantation Outcomes and Treatments
- Genomics, phytochemicals, and oxidative stress
Duke University
2018-2025
Duke Medical Center
2021-2023
Durham VA Medical Center
2022
RELX Group (United States)
2021
Duke University Hospital
2021
Northwestern University
2015-2020
Renal Research Institute
2018-2019
Tohoku University
2009-2017
Cardiovascular Institute Hospital
2016-2017
Hypertension Institute
2017
Abnormal cellular accumulation of the dicarbonyl metabolite MG (methylglyoxal) occurs on exposure to high glucose concentrations, inflammation, cell aging and senescence. It is associated with increased MG-adduct content protein DNA linked strand breaks mutagenesis, mitochondrial dysfunction ROS (reactive oxygen species) formation detachment from extracellular matrix. MG-mediated damage countered by glutathione-dependent metabolism Glo1 (glyoxalase 1). not known, however, whether has...
Primary congenital glaucoma (PCG) is a devastating eye disease and an important cause of childhood blindness worldwide. In PCG, defects in the anterior chamber aqueous humor outflow structures result elevated intraocular pressure (IOP); however, genes molecular mechanisms involved etiology these have not been fully characterized. Previously, we observed PCG-like phenotypes transgenic mice that lack functional angiopoietin-TEK signaling. Herein, identified rare TEK variants 10 189 unrelated...
Background and objectives Per- polyfluoroalkyl substances (PFASs) are a large group of manufactured nonbiodegradable compounds. Despite increasing awareness as global pollutants, the impact PFAS exposure on human health is not well understood, there growing concerns for adverse effects kidney function. Therefore, we conducted scoping review to summarize identify gaps in understanding between health. Design, setting, participants, & measurements We systematically searched PubMed, EMBASE,...
Overwhelming lipid peroxidation induces ferroptotic stress and ferroptosis, a non-apoptotic form of regulated cell death that has been implicated in maladaptive renal repair mice humans. Using single-cell transcriptomic mouse genetic approaches, we show proximal tubular (PT) cells develop molecularly distinct, pro-inflammatory state following injury. While these inflammatory PT transiently appear after mild injury return to their original without inducing fibrosis, severe they accumulate...
CKD progresses with fibrosis and erythropoietin (Epo)-dependent anemia, leading to increased cardiovascular complications, but the mechanisms linking Epo-dependent anemia remain unclear. Here, we show that cellular phenotype of renal Epo-producing cells (REPs) alternates between a physiologic state pathologic fibrogenic in response microenvironmental signals. In novel mouse model, unilateral ureteral obstruction–induced inflammatory milieu activated NFκB Smad signaling pathways REPs, rapidly...
Erythropoietin (Epo) is produced by renal Epo-producing cells (REPs) in a hypoxia-inducible manner. The conversion of REPs into myofibroblasts and coincident loss ability are the major cause fibrosis anemia. However, hypoxic response these transformed remains unclear. Here, we used complementary vivo transgenic live imaging approaches to better understand importance hypoxia signaling Epo production. Live mice expressing green fluorescent protein from modified Epo-gene locus revealed that...
Primary congenital glaucoma (PCG) is a leading cause of blindness in children worldwide and caused by developmental defects 2 aqueous humor outflow structures, Schlemm's canal (SC) the trabecular meshwork. We previously identified loss-of-function mutations angiopoietin (ANGPT) receptor TEK families with PCG showed that ANGPT/TEK signaling essential for SC development. Here, we describe roles major ANGPT ligands development pathway. determined ANGPT1 development, Angpt1-knockout mice form...
Significance Reducing vascular leakage and stabilizing the endothelium through activation of angiopoietin (ANGPT)–TIE2 receptor tyrosine kinase pathway is a promising therapeutic strategy for diseases. ANGPT2 one two major ligands TIE2 receptor. Uniquely, possesses an agonistic role in lymphatic endothelium, but acts as competitive antagonist blood endothelium. The molecular basis opposing actions these beds poorly understood. Here we demonstrate that absence VEPTP expression confers agonist...
In both humans and mice, repair of acute kidney injury is worse in males than females. Here, we provide evidence that this sexual dimorphism results from sex differences ferroptosis, an iron-dependent, lipid-peroxidation-driven regulated cell death. Using genetic single-cell transcriptomic approaches report female confers striking protection against which was experimentally induced proximal tubular (PT) cells by deleting glutathione peroxidase 4 (Gpx4). Single-cell analyses further identify...
Hypertension in patients with chronic kidney disease (CKD) strongly associates cardiovascular events. Among CKD, reducing the accumulation of uremic toxins may protect against development hypertension and progression renal damage, but there are no established therapies to accomplish this. Here, overexpression human kidney-specific organic anion transporter SLCO4C1 rat reduced hypertension, cardiomegaly, inflammation setting failure. In addition, decreased plasma levels guanidino succinate,...
Placental activation of the renin-angiotensin system (RAS) plays a key role in pathogenesis preeclampsia. Reactive oxygen species (ROS) are thought to affect placental angiogenesis, which is critical for preventing preeclampsia pathology. We examined ROS by genetically modifying Keap1-Nrf2 pathway, cellular antioxidant defense system, mouse model RAS-induced Nrf2 deficiency would be expected impair responses; however, preeclamptic mice improved maternal and fetal survival, ameliorated...
Erythropoietin (Epo) is produced in the kidney and liver a hypoxia-inducible manner via activation of transcription factors (HIFs) to maintain oxygen homeostasis. Accelerating Epo production hepatocytes one plausible therapeutic strategy for treating anemia caused by diseases. To elucidate regulatory mechanisms hepatic production, we analyzed mouse lines harboring liver-specific deletions genes encoding HIF-prolyl-hydroxylase isoforms (PHD1, PHD2, PHD3) that mediate inactivation HIF1α HIF2α...
Vitamin D regulates mineral homeostasis. The most biologically active form of vitamin D, 1,25-dihydroxyvitamin (1,25D), is synthesized by CYP27B1 from 25-dihydroxyvitamin (25D) and inactivated CYP24A1. Human monogenic diseases genome-wide association studies support a critical role for CYP24A1 in regulation homeostasis, but little known about its tissue-specific effects. Here, we describe the responses mice with inducible global deletion, kidney-specific, intestine-specific deletion Cyp24a1...
Purpose: Affecting children by age 3, primary congenital glaucoma (PCG) can cause debilitating vision loss the developmental impairment of aqueous drainage resulting in high intraocular pressure (IOP), globe enlargement, and optic neuropathy. TEK haploinsufficiency accounts for 5% PCG diverse populations, with low penetrance explained variable dysgenesis Schlemm's canal (SC) mice. We report eight families TEK-related PCG, provide evidence SVEP1 as a disease modifier family 8 higher severity....
Diabetic nephropathy is a leading cause of end-stage kidney failure. Reduced angiopoietin-TIE2 receptor tyrosine kinase signaling in the vasculature leads to increased vascular permeability, inflammation, and endothelial cell loss associated with development diabetic complications. Here, we identified mechanism explain how TIE2 attenuated animals. Expression protein phosphatase VE-PTP (also known as PTPRB), which dephosphorylates TIE2, robustly up-regulated renal microvasculature rodents,...
Methylglyoxal (MGO) is a non-enzymatic metabolite in the glycolytic pathway and its concentration blood tissues elevated diabetes renal failure. MGO induces tissue injuries via ROS; however, mechanism remains to be clarified. The present study examined harmful actions of MGO. Human aortic endothelial cells were assessed under real-time fluorescent microscopy with continuous superfusion. Increases intracellular ROS measured indicator, 5-(and-6)-chloromethyl-2',7'-dichlorodihydrofluorescein...
Renal macrophages represent a highly heterogeneous and specialized population of myeloid cells with mixed developmental origins from the yolk-sac hematopoietic stem (HSC). They promote both injury repair by regulating inflammation, angiogenesis, tissue remodeling. Recent reports highlight differential roles for ontogenically distinct renal macrophage populations in disease. However, little is known about how these change over time normal, uninjured kidneys. Prior demonstrated high proportion...
The transcription factor GATA2 plays pivotal roles in early renal development, but its distribution and physiological functions adult kidney are largely unknown. We examined the expression pattern by tracing green fluorescent protein (GFP) fluorescence Gata2(GFP/+) mice that recapitulate endogenous found a robust GFP specifically medulla. Upon purification of GFP-positive cells, we collecting duct (CD)-specific markers, including aquaporin 2 (Aqp2), an important channel for water...