A5069369057- Ion Transport and Channel Regulation
- Ion channel regulation and function
- Electrolyte and hormonal disorders
- Hormonal Regulation and Hypertension
- Renal and related cancers
- Cardiac electrophysiology and arrhythmias
- Sodium Intake and Health
- Magnesium in Health and Disease
- Potassium and Related Disorders
- Renal function and acid-base balance
- Cellular transport and secretion
- Genetic and Kidney Cyst Diseases
- Renin-Angiotensin System Studies
- Erythrocyte Function and Pathophysiology
- Single-cell and spatial transcriptomics
- Chronic Kidney Disease and Diabetes
- COVID-19 Clinical Research Studies
- Neuroscience and Neuropharmacology Research
- Pancreatic function and diabetes
- Parathyroid Disorders and Treatments
- Birth, Development, and Health
- Lipid Membrane Structure and Behavior
- Endoplasmic Reticulum Stress and Disease
- Neuroscience and Neural Engineering
- Biomedical Research and Pathophysiology
Johns Hopkins University
2019-2025
Johns Hopkins Medicine
2020-2025
University of Maryland, Baltimore
2010-2019
University of Maryland, College Park
2018
Yale University
1992-2017
University Hospital Cologne
2012
University of Baltimore
2004
University of California, San Francisco
2004
University of Kansas
1984-2002
Commissariat à l'Énergie Atomique et aux Énergies Alternatives
2001
Diabetic nephropathy is characterized by damage to both the glomerulus and tubulointerstitium, but relatively little known about accompanying cell-specific changes in gene expression. We performed unbiased single-nucleus RNA sequencing (snRNA-seq) on cryopreserved human diabetic kidney samples generate 23,980 transcriptomes from 3 control early samples. All major cell types of were represented final dataset. Side-by-side comparison demonstrated cell-type-specific expression that are...
Hypertension places a major burden on individual and public health, but the genetic basis of this complex disorder is poorly understood. We conducted genome-wide association study systolic diastolic blood pressure (SBP DBP) in Amish subjects found strong signals with common variants serine/threonine kinase gene, STK39 . confirmed an independent 4 non-Amish Caucasian samples including Diabetes Genetics Initiative, Framingham Heart Study, GenNet, Hutterites (meta-analysis combining all...
Aberrant activation of with no lysine (WNK) kinases causes familial hyperkalemic hypertension (FHHt). Thiazide diuretics treat the disease, fostering view that hyperactivation thiazide-sensitive sodium-chloride cotransporter (NCC) in distal convoluted tubule (DCT) is solely responsible. However, aberrant signaling aldosterone-sensitive nephron (ASDN) and inhibition potassium-excretory renal outer medullary potassium (ROMK) channel have also been implicated. To test these ideas, we introduced...
There has been much speculation in journals, as well social and traditional media about a link between popularly used classes of drugs that inhibit the renin-angiotensin system (RAS) novel coronavirus (severe acute respiratory syndrome 2 [SARS-CoV-2]) infection or disease 2019 (COVID-19) severity (1,2). After examining available evidence, we advise inhibitors RAS pathway should be continued patients with COVID-19 who are taking these for evidence-based indications. The putative SARS-CoV-2...
Thiazide diuretics are used to treat hypertension; however, compensatory processes in the kidney can limit antihypertensive responses this class of drugs. Here, we evaluated pathways SPAK kinase-deficient mice, which unable activate thiazide-sensitive sodium chloride cotransporter NCC (encoded by Slc12a3). Global transcriptional profiling, combined with biochemical, cell biological, and physiological phenotyping, identified gene expression signature response revealed how it establishes an...
Abstract Autosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of end stage renal characterized by progressive expansion cysts. To better understand cell types and states driving ADPKD progression, we analyze eight five healthy human samples, generating single multiomic atlas consisting ~100,000 nucleus transcriptomes ~50,000 epigenomes. Activation proinflammatory, profibrotic signaling pathways are driven proximal tubular cells with a failed repair transcriptomic...
Background: Discovering metabolomic markers of dietary potassium may help improve assessment and trace the impact on chronic kidney disease (CKD) development. Methods: We included adults from Atherosclerosis Risk in Communities (ARIC) study without CKD at visit 1 ( N = 3,812). Cross-sectional associations between serum metabolites were assessed using multivariable linear regression models. Cox models estimated hazard ratios for potassium-related incident CKD. Incident was defined as...
The Kir1.1 (ROMK) subtypes of inward rectifier K+ channels mediate potassium secretion and regulate sodium chloride reabsorption in the kidney. density ROMK on cortical collecting duct apical membrane is exquisitely regulated concert with physiological demands. Although protein kinase A-dependent phosphorylation one three phospho-acceptors Kir1.1, Ser-44, also a canonical serum-glucocorticoid-regulated (SGK-1) site, controls number active channels, it unknown whether this involves activating...
A fundamental and essential property of nearly all salt-transporting epithelia is the tight parallel coupling between magnitude K-conductive pathway at basolateral membrane activity Na,K-dependent ATPase (Na,K-ATPase). In present study, we demonstrate that response in renal proximal tubule governed, least part, through interaction ATP-sensitive K channels Na,K-ATPase-mediated changes intracellular ATP levels. First, identified a K-selective channel membrane, which inhibited by cytosolic...
Na(+)/H(+) exchanger regulatory factor (NHERF) and NHERF2 are PDZ motif proteins that mediate the inhibitory effect of cAMP on 3 (NHE3) by facilitating formation a multiprotein signaling complex. With use antibodies specific for NHERF NHERF2, immunocytochemical analysis rat kidney was undertaken to determine nephron distribution both their colocalization with other transporters ezrin. most abundant in apical membrane proximal tubule cells, where it colocalized ezrin NHE3. detected glomerulus...
Members of the WNK family serine/threonine kinases have been implicated as important modulators salt homeostasis, regulating balance between renal sodium reabsorption and potassium excretion. Gain-of-expression mutations in WNK1 gene uncouple Na(+) K(+) cause a familial disorder diminished excretion, excessive retention, hypertension (pseudohypoaldosteronism type II or Gordon's syndrome). Alternative splicing produces kidney-specific short form (KS-WNK1) more ubiquitous long (L-WNK1), but it...
ROMK channels are well-known to play a central role in renal K secretion, but the absence of highly specific and avid-ROMK antibodies has presented significant roadblocks toward mapping extent expression along entire distal nephron determining whether surface density these is regulated response physiological stimuli. Here, we prepared new verified be specific, using knockout mice as control. Characterization with segmental markers revealed more extensive pattern than previously thought,...
Background Hyperkalemia in association with metabolic acidosis that are out of proportion to changes glomerular filtration rate defines type 4 renal tubular (RTA), the most common RTA observed, but molecular mechanisms underlying associated incompletely understood. We sought determine whether hyperkalemia directly causes and, if so, through which this occurs. Methods studied a genetic model results from early distal convoluted tubule (DCT)–specific overexpression constitutively active...
Proteomic profiling may allow identification of plasma proteins that associate with subsequent changesin kidney function, elucidating biologic processes underlying the development and progression CKD.We quantified association between 4877 a composite outcome ESKD or decline in eGFR by ≥50% among 9406 participants Atherosclerosis Risk Communities (ARIC) Study (visit 3; mean age, 60 years) who were followed for median 14.4 years. We performed separate analyses these subset 4378 5), at later...
Significance Statement Measurement of urinary extracellular vesicle (uEV) protein abundances is frequently used to reflect ongoing (patho)physiologic processes in the kidney. However, whether uEVs and kidney directly correlate, or alterations levels can be determined by assessing changes uEVs, has never been comprehensively determined. Here, quantitative proteomic data indicate rats are correlated, with a monotonic relationship between altered transporter abundance after physiologic...
Dietary potassium (K+) supplementation is associated with a lowering effect in blood pressure (BP), but not all studies agree. Here, we examined the effects of short- and long-term K+ on BP mice, whether differences depend accompanying anion or sodium (Na+) intake molecular alterations kidney that may underlie changes. Relative to control diet, was higher mice fed high NaCl (1.57% Na+) diet for 7 weeks K+-free 2 weeks. highest K+-free/high diet. Commensurate increased abundance...
Potassium regulates the WNK (with no lysine kinase)-SPAK (STE20/SPS1-related proline/alanine-rich kinase) signaling axis, which in turn controls phosphorylation and activation of distal convoluted tubule thiazide-sensitive NCC (sodium-chloride cotransporter) for sodium-potassium balance. Although their roles kidney have not been investigated, it has postulated that Cab39 (calcium-binding protein 39) or Cab39l (Cab39-like) is required SPAK/OSR1 (oxidative stress response 1) activation. This...