A5010081724- Renal Diseases and Glomerulopathies
- Chronic Kidney Disease and Diabetes
- Lymphoma Diagnosis and Treatment
- RNA modifications and cancer
- Ubiquitin and proteasome pathways
- Bioinformatics and Genomic Networks
- Renal and related cancers
- RNA Research and Splicing
- Genetic Associations and Epidemiology
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Single-cell and spatial transcriptomics
- Glycosylation and Glycoproteins Research
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Cancer Research and Treatments
- Cancer Genomics and Diagnostics
- Gene expression and cancer classification
- Birth, Development, and Health
- Ion Transport and Channel Regulation
- RNA Interference and Gene Delivery
- Lipid metabolism and disorders
- Chronic Lymphocytic Leukemia Research
- Cell Adhesion Molecules Research
- Advanced Proteomics Techniques and Applications
- Cancer-related gene regulation
- Epigenetics and DNA Methylation
University of Michigan
2015-2025
Duke University
2024
Michigan United
2010-2024
Michigan Medicine
2018-2024
Duke Medical Center
2024
Michigan Center for Translational Pathology
2021
Yale University
2017
University of Iowa
2015
University of California, Davis
2015
National University Health System
2013
Significance Statement Although corticosteroids are an effective first-line therapy for minimal change disease, relapse, steroid dependence, and intolerance common in this podocytopathy of unknown etiology. The efficacy B cell–targeted therapies some patients suggests autoantibody-mediated This study describes the novel discovery both adults children with disease autoantibodies targeting nephrin, a critical component podocyte slit diaphragm that ensures integrity glomerular filtration...
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...
Summary Calorie restriction (CR) increases lifespan in organisms ranging from budding yeast through mammals. Mitochondrial adaptation represents a key component of the response to CR. Molecular mechanisms underlying this are largely unknown. Here we show that lysine acetylation mitochondrial proteins is altered during CR tissue‐specific fashion. Via large‐scale mass spectrometry screening, identify 72 candidate involved variety metabolic pathways with changes may play an important role...
Annual influenza vaccinations are currently recommended for all individuals 6 months and older. Antibodies induced by vaccination an important mechanism of protection against infection. Despite the overall public health success vaccination, many fail to induce a substantial antibody response. Systems-level immune profiling studies have discerned associations between transcriptional cell subset signatures with responses. However, existing relied on small cohorts not been validated in large...
Abstract Computational tools for multiomics data integration have usually been designed unsupervised detection of features explaining large phenotypic variations. To achieve this, some approaches extract latent signals in heterogeneous sets from a joint statistical error model, while others use biological networks to propagate differential expression and find consensus signatures. However, few directly consider molecular interaction as feature, the essential linker between different omics...
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...
A contiguous assembly of the inbred 'EL10' sugar beet (Beta vulgaris ssp. vulgaris) genome was constructed using PacBio long-read sequencing, BioNano optical mapping, Hi-C scaffolding, and Illumina short-read error correction. The EL10.1 540 Mb, which 96.2% contained in nine chromosome-sized pseudomolecules with lengths from 52 to 65 31 contigs a median size 282 kb that remained unassembled. Gene annotation incorporating RNA-seq data curated sequences via MAKER pipeline generated 24,255 gene...
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...
Sparsentan, a dual endothelin receptor A inhibitor and angiotensin blocker, reduced proteinuria in patients with focal segmental glomerulosclerosis (FSGS) Phase II III studies. However, the estimated glomerular filtration rate (eGFR) endpoint was not achieved, partially attributed to disease heterogeneity among participants. Sparsentan reversed molecular fingerprint kidneys of an adriamycin-challenged rat model chronic kidney disease, consistent phenotypic data. Transcriptomic profiles from...
Chronic kidney diseases (CKDs) are a global health concern, necessitating comprehensive understanding of their complex pathophysiology. This study explores the use 2 complementary multidimensional -omics data integration methods to elucidate mechanisms CKD progression as proof concept. Baseline biosamples from 37 participants with in Clinical Phenotyping and Resource Biobank Core (C-PROBE) cohort prospective longitudinal outcome ascertained over 5 years were used generate molecular profiles....
Identification of biomarkers and therapeutic targets is a critical goal precision medicine. N-glycoproteins are particularly attractive class proteins that constitute potential cancer for small molecules, antibodies, cellular therapies. Using mass spectrometry (MS), we generated compendium 1,091 (from 40 human primary lymphomas cell lines). Hierarchical clustering revealed distinct subtype signatures included several subtype-specific biomarkers. Orthogonal immunological studies in 671...
Focal segmental glomerulosclerosis (FSGS) is a common cause of end-stage kidney disease (ESKD) across the lifespan. While 10% to 15% children and 3% adults who develop ESKD have FSGS, it remains uncertain whether natural history differs in pediatric vs adult patients, this uncertainty contributes exclusion adolescents clinical trials.
Hyperfiltration is a state of high glomerular filtration rate (GFR) observed in early diabetes that damages glomeruli, resulting an iterative process increasing load on fewer and remaining functional glomeruli. To delineate underlying cellular mechanisms damage associated with hyperfiltration, transcriptional profiles kidney biopsies from Pima Indians type 2 or without early-stage diabetic disease were grouped into two hyperfiltration categories based annual iothalamate GFR measurements....
Kidney organoids are a promising model to study kidney disease, but their use is constrained by limited knowledge of functional protein expression profile. Here, we define the organoid proteome and transcriptome trajectories over culture duration upon exposure TNFα, cytokine stressor. Older increase deposition extracellular matrix decrease glomerular proteins. Single cell integration reveals that most changes localize podocytes, tubular stromal cells. TNFα treatment results in 322...