A5018962385- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- Renal and related cancers
- Diabetes Treatment and Management
- Genetic Associations and Epidemiology
- Birth, Development, and Health
- Single-cell and spatial transcriptomics
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Diabetes and associated disorders
- Pancreatic function and diabetes
- Systemic Lupus Erythematosus Research
- Lipid metabolism and disorders
- Liver Disease Diagnosis and Treatment
- Dialysis and Renal Disease Management
- Genetic Syndromes and Imprinting
- Parathyroid Disorders and Treatments
- Ion Transport and Channel Regulation
- Metabolism, Diabetes, and Cancer
- Epigenetics and DNA Methylation
- GDF15 and Related Biomarkers
- Genetic and Kidney Cyst Diseases
- Cell Adhesion Molecules Research
- Electrolyte and hormonal disorders
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Apelin-related biomedical research
University of Michigan
2016-2025
Centre for Science and Environment
2024
Michigan Medicine
2018-2024
Michigan United
2010-2024
CMR University
2024
Ludwig-Maximilians-Universität München
2022
Michigan Center for Translational Pathology
2020
National Cancer Council Malaysia
2018
Ann Arbor Center for Independent Living
2018
Pediatric Nephrology of Alabama
2014
Renal and urinary EGF can serve as biomarkers for prediction of outcomes in chronic kidney disease.
Cell-lineage-specific transcripts are essential for differentiated tissue function, implicated in hereditary organ failure, and mediate acquired chronic diseases. However, experimental identification of cell-lineage-specific genes a genome-scale manner is infeasible most solid human tissues. We developed the first method to identify with expression, even lineages not separable by microdissection. Our machine-learning-based approach leverages high-throughput data from homogenates novel...
Diabetes is associated with altered cellular metabolism, but how metabolism contributes to the development of diabetic complications unknown. We used BKS db/db mouse model investigate changes in carbohydrate and lipid kidney cortex, peripheral nerve, retina. A systems approach using transcriptomics, metabolomics, metabolic flux analysis identified tissue-specific differences, increased glucose fatty acid kidney, a moderate increase retina, decrease nerve. In was enhanced protein acetylation...
Significance Statement Although studies show that diabetic kidney disease has a heritable component, searches for the genetic determinants of this complication diabetes have had limited success. In study, new international genomics consortium, JDRF funded Diabetic Nephropathy Collaborative Research Initiative, assembled nearly 20,000 samples from participants with type 1 diabetes, and without disease. The authors found 16 disease–associated loci at genome-wide significance. strongest signal...
To define cellular mechanisms underlying kidney function and failure, the KPMP analyzes biopsy tissue in a multicenter research network to build cell-level process maps of kidney. This study aimed establish single cell RNA sequencing strategy use transcriptional profiles from biopsies molecular subtypes glomerular diseases. Using multiple sources adult human reference samples, 22,268 passed quality control parameters. Unbiased clustering resulted 31 distinct clusters that were linked immune...
The molecular mechanisms of sodium-glucose cotransporter-2 (SGLT2) inhibitors (SGLT2i) remain incompletely understood. Single-cell RNA sequencing and morphometric data were collected from research kidney biopsies donated by young persons with type 2 diabetes (T2D), aged 12 to 21 years, healthy controls (HCs). Participants T2D obese had higher estimated glomerular filtration rates mesangial volumes than HCs. Ten participants been prescribed SGLT2i (T2Di[+]) 6 not (T2Di[-]). Transcriptional...
Lupus nephritis (LN) is a serious manifestation of systemic lupus erythematosus. Therapeutic studies in mouse LN models do not always predict outcomes human therapeutic trials, raising concerns about the relevance these preclinical models. In this study, we used an unbiased transcriptional network approach to define, molecular terms, similarities and differences among three LN. Genome-wide gene-expression networks were generated using natural language processing automated promoter analysis...
Murine models are valuable instruments in defining the pathogenesis of diabetic nephropathy (DN), but they only partially recapitulate disease manifestations human DN, limiting their utility. To define molecular similarities and differences between murine we performed a cross-species comparison glomerular transcriptional networks. Glomerular gene expression was profiled patients with early type 2 DN three mouse (streptozotocin DBA/2, C57BLKS db/db, eNOS-deficient db/db mice)....
Growth differentiation factor-15 (GDF-15) is a member of the TGF-β cytokine superfamily that widely expressed and may be induced in response to tissue injury. Elevations GDF-15 identify novel pathway involved loss kidney function among patients with CKD. Among participants Clinical Phenotyping Resource Biobank (C-PROBE) study Seattle Kidney Study (SKS), we tested whether expression GDF15 mRNA correlates circulating levels elevations are associated decline function. In matching samples 24 CKD...
Diabetic kidney disease (DKD) remains the most common cause of end-stage despite multifactorial intervention. We demonstrated that increased cholesterol in association with downregulation ATP-binding cassette transporter ABCA1 occurs normal human podocytes exposed to sera patients type 1 diabetes and albuminuria (DKD(+)) when compared diabetic normoalbuminuria (DKD(-)) similar duration lipid profile. Glomerular was confirmed biopsies from early DKD (n = 70) living donors 32). Induction...
Fibroblasts from patients with Tangier disease carrying ATP-binding cassette A1 (ABCA1) loss-of-function mutations are characterized by cardiolipin accumulation, a mitochondrial-specific phospholipid. Suppression of ABCA1 expression occurs in glomeruli diabetic kidney (DKD) and human podocytes exposed to DKD sera collected prior the development DKD. We demonstrated that siRNA knockdown led reduced oxygen consumption capabilities associated alterations oxidative phosphorylation (OXPHOS)...
TGF-β1 is a pleotropic growth factor that mediates glomerulosclerosis and podocyte apoptosis, hallmarks of glomerular diseases. The expression microRNA-21 (miR-21) regulated by TGF-β1, miR-21 inhibits apoptosis in cancer cells. TGF-β1–transgenic mice exhibit accelerated loss glomerulosclerosis. We determined increases rapidly cultured murine podocytes after exposure to higher kidneys than wild-type mice. miR-21–deficient showed increased proteinuria extracellular matrix deposition fewer per...
A previous meta-analysis of genome-wide association data by the Cohorts for Heart and Aging Research in Genomic Epidemiology CKDGen consortia identified 16 loci associated with eGFR. To define how each these single-nucleotide polymorphisms (SNPs) could affect renal function, we integrated GFR-associated regulatory pathways, producing a molecular map CKD. In kidney biopsy specimens from 157 European subjects representing nine different CKDs, transcript levels 18 genes proximity to SNPs...
APOL1 variants have been associated with renal phenotypes in blacks. To refine clinical outcomes and discover mechanisms of APOL1-associated kidney injury, we analyzed genomic datasets derived from 90 black subjects the Nephrotic Syndrome Study Network (NEPTUNE), stratified by risk genotype. Ninety proteinuria ≥0.5 g/d were enrolled at first biopsy for primary nephrotic syndrome followed. Clinical determined, histomorphometry sequencing Mendelian genes performed. genotyped, glomerular...
BACKGROUND. In this study, we identified the lipidomic predictors of early type 2 diabetic kidney disease (DKD) progression, which are currently undefined.
Podocyte injury is central to many forms of kidney disease, but transcriptional signatures reflecting podocyte and compensation mechanisms are challenging analyze in vivo. Human organoids derived from pluripotent stem cells (PSCs), a potentially new model for disease regeneration, present an opportunity explore the plasticity podocytes. Here, profiling more than 12,000 single human PSC–derived organoid cultures was used identify robust reproducible cell lineage gene expression shared with...
COVID-19 morbidity and mortality are increased via unknown mechanisms in patients with diabetes kidney disease. SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) for entry into host cells. Because ACE2 is a susceptibility factor infection, we investigated how diabetic disease medications alter receptor expression kidneys. Single cell RNA profiling of biopsies from healthy living donors revealed primarily proximal tubular epithelial This cell-specific localization was confirmed by situ...
The diagnosis of nephrotic syndrome relies on clinical presentation and descriptive patterns injury kidney biopsies, but not specific to underlying pathobiology. Consequently, there are variable rates progression response therapy within diagnoses. Here, an unbiased transcriptomic-driven approach was used identify molecular pathways which shared by subgroups patients with either minimal change disease (MCD) or focal segmental glomerulosclerosis (FSGS). Kidney tissue transcriptomic...
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease, and histopathologic glomerular lesions are among earliest structural alterations DN. However, signaling pathways that initiate these incompletely understood.To delineate cellular molecular basis for DN initiation, we performed single-cell bulk RNA sequencing cells from type 2 diabetes mice (BTBR ob/ob) at early stage DN.Analysis differentially expressed genes revealed glucose-independent responses in cell types. The...
Current classification of chronic kidney disease (CKD) into stages using indirect systemic measures (estimated glomerular filtration rate (eGFR) and albuminuria) is agnostic to the heterogeneity underlying molecular processes in thereby limiting precision medicine approaches. To generate a novel CKD categorization that directly reflects within drivers we analyzed publicly available transcriptomic data from biopsy tissue. A Self-Organizing Maps unsupervised artificial neural network...