A5091542186- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- Renal and related cancers
- Single-cell and spatial transcriptomics
- Cancer Genomics and Diagnostics
- Vasculitis and related conditions
- Systemic Lupus Erythematosus Research
- Adipose Tissue and Metabolism
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Lung Cancer Treatments and Mutations
- Ion Transport and Channel Regulation
- Bioinformatics and Genomic Networks
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cell Adhesion Molecules Research
- Biomedical Ethics and Regulation
- Pancreatic function and diabetes
- Gene expression and cancer classification
- Diabetes Treatment and Management
- Adipokines, Inflammation, and Metabolic Diseases
- Renal cell carcinoma treatment
- Radiomics and Machine Learning in Medical Imaging
- NF-κB Signaling Pathways
- Bat Biology and Ecology Studies
- Pancreatic and Hepatic Oncology Research
- Cytokine Signaling Pathways and Interactions
University of Michigan
2016-2025
Cohen Children's Medical Center
2024
Michigan United
2019-2024
Michigan Medicine
2018-2024
University of Washington Medical Center
2021
Thermo Fisher Scientific (United States)
2014
Vall d'Hebron Institute of Oncology
2012
University of Alabama at Birmingham
2012
Selventa (United States)
2011
Boston University
2005-2008
Abstract Understanding kidney disease relies on defining the complexity of cell types and states, their associated molecular profiles interactions within tissue neighbourhoods 1 . Here we applied multiple single-cell single-nucleus assays (>400,000 nuclei or cells) spatial imaging technologies to a broad spectrum healthy reference kidneys (45 donors) diseased (48 patients). This has provided high-resolution cellular atlas 51 main types, which include rare previously undescribed...
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...
Abstract Chronic kidney disease (CKD) is a public health problem driven by myofibroblast accumulation, leading to interstitial fibrosis. Heterogeneity recently recognized characteristic in fibroblasts CKD, but the role of different populations still unclear. Here, we characterize proinflammatory fibroblast population (named CXCL-iFibro), which corresponds an early state differentiation CKD. We demonstrate that CXCL-iFibro co-localize with macrophages and participate their attraction, switch...
High levels of circulating TNF and its receptors, TNFR1 TNFR2, predict the progression diabetic kidney disease (DKD), but their contribution to organ damage in DKD remains largely unknown. Here, we investigated function local systemic podocyte injury. We cultured human podocytes with sera collected from patients, who displayed elevated levels, focal segmental glomerulosclerosis (FSGS) whose resembled those healthy patients. Exogenous administration or expression was equally sufficient cause...
<h3>Objectives</h3> To characterise renal tissue metabolic pathway gene expression in different forms of glomerulonephritis. <h3>Methods</h3> Patients with nephrotic syndrome (NS), antineutrophil cytoplasmic antibody-associated vasculitis (AAV), systemic lupus erythematosus (SLE) and healthy living donors (LD) were studied. Clinically indicated biopsies obtained at time diagnosis microdissected into glomerular tubulointerstitial compartments. Microarray-derived differential 88 genes...
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...
Abstract Understanding kidney disease relies upon defining the complexity of cell types and states, their associated molecular profiles, interactions within tissue neighborhoods. We have applied multiple single-cell or -nucleus assays (>400,000 nuclei/cells) spatial imaging technologies to a broad spectrum healthy reference (n = 42) kidneys. This has provided high resolution cellular atlas 100 that include rare novel populations. The multi-omic approach provides detailed transcriptomic...
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...
Significance Statement A signaling molecule that plays a role in the innate immune system, stimulator of IFN genes (STING), is crucial regulator cyclic GMP-AMP synthase (cGAS)-STING pathway. This pathway regulates inflammation and energy homeostasis under conditions obesity, kidney fibrosis, AKI, but its exact pathogenesis glomerular diseases remains unclear. The authors found activation STING wild-type mice sufficient to cause albuminuria podocyte loss, cGAS-STING upregulated with...
Glomerular diseases are classified using a descriptive taxonomy that is not reflective of the heterogeneous underlying molecular drivers. This limits only diagnostic and therapeutic patient management, but also impacts clinical trials evaluating targeted interventions. The Nephrotic Syndrome Study Network (NEPTUNE) poised to address these challenges. study has enrolled >850 pediatric adult patients with proteinuric glomerular who have contributed deep clinical, histologic, genetic, profiles...
Abstract Aberrant activation of nuclear factor-κB (NF-κB) transcription factors has been implicated in the pathogenesis breast cancer. We previously showed elevated activity IκB kinase α (IKKα), IKKβ, and protein CK2 primary human cancer specimens cultured cells. A novel inducible IKK termed IKK-i/IKKε characterized as a potential NF-κB activator. Here, we provide evidence that implicates show expression carcinogen-induced mouse mammary tumors. Multiple cell lines higher levels compared with...
IntroductionIndividuals with focal segmental glomerular sclerosis (FSGS) typically undergo kidney biopsy only once, which limits the ability to characterize cell gene expression over time.MethodsWe used single-cell RNA sequencing (scRNA-seq) explore disease-related molecular signatures in urine cells from subjects FSGS. We collected 17 samples 12 FSGS and captured these as 23 samples. The inflammatory renal epithelial immune were evaluated bulk data sets of minimal change disease (MCD) (The...
Abstract Background Critical to advancing the systems-level evaluation of complex biological processes is development comprehensive networks and computational methods apply analysis systems biology data (transcriptomics, proteomics/phosphoproteomics, metabolomics, etc.). Ideally, these will be specifically designed capture normal, non-diseased tissue or cell types under investigation, can used with experimentally generated assess impact perturbations like xenobiotics other cellular stresses....
Aberrant constitutive expression of NF-kappaB subunits, reported in more than 90% breast cancers and multiple other malignancies, plays pivotal roles tumorigenesis. Higher RelB subunit was demonstrated estrogen receptor alpha (ERalpha)-negative versus ERalpha-positive ones, due part to repression synthesis by ERalpha signaling. Notably, promoted a invasive phenotype ERalpha-negative via induction the BCL2 gene. We report here that reciprocally inhibits cancer cells, which contributes...
Abstract Overexpression of the epidermal growth factor receptor family member HER2 is found in ∼30% breast cancers and a target for immunotherapy. Trastuzumab, humanized monoclonal antibody against HER2, cytostatic when added alone highly successful clinical settings used combination with other chemotherapeutic agents. Unfortunately, tumors patients develop resistance to trastuzumab or metastasize brain, which inaccessible therapy. Previously, we showed that green tea polyphenol...