Development and Optimization of Near Single Cell Proteome of Diabetic Nephropathy
Diabetes is projected to be a major health crisis in near future. People with diabetes are more likely to have both microvascular and macrovascular complications, including diabetic kidney disease (DKD). The incidence of occurring DKD on diabetic individuals is estimated to be ~40% and triggers kidney-specific diseases such as glomerular hypertrophy, glomerulosclerosis, and tubulointerstitial inflammation and fibrosis. Despite current therapies, there is an urgent need to understand the risk of disease onset and progression. Building of a molecular/cellular atlas integrating imaging and “omics” datasets provides a promise for a comprehensive picture of kidney at pertinent clinical endpoints. This carefully designed study brings a team of expert investigators who have access to the best facilities in carrying the proposed work. We aim to develop and generate proteomics data at near single cell level interrogating the cells captured from glomeruli. Through this study, we will be able dive deep into the DKD-associated processes in glomerular cells such as mesangial expansion, glomerular basement membrane thickening and fibrosis. The protocol developed through this study will be helpful to capture more kidney cell types for proteome profiling in the future. The unbiased and high throughput interrogation of glomerular cells at different clinical endpoints of DKD (stages I-IV) will generate proteome data for hypothesis generation. The additional contribution is that this proteome data will be instrumental in providing a dimension among many dimensions of molecular integration through imaging and other omics such as transcriptomics and metabolomics. The hypotheses generated could be applied to larger studies with funding from NIH and non-NIH sources.

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