Project description:This project aims to evaluate the association between environmental exposure to perfluorinated alkyl substances (PFCs) and the development of risk factors for cardiometabolic disease in youth diagnosed with diabetes in the SEARCH Cohort Study. The longitudinal study of newly diagnosed cases of type 1 and type 2 diabetes examines serum metabolome changes at baseline and follow-up at approximately 5 years (all >3 years from baseline). Exposures to PFCs and biological effects characterized by serum metabolome changes will be associated with known cardiometabolic risk factors in youth diagnosed with diabetes.
Project description:Processing of the dataset of synthetic phosphopeptides by Savitzki et al. (MCP, 2011) using multiple search engines. Establishment of the D-score: a search engine independent MD-score.
Project description:Single cell RNA-sequencing analysis allows for a more complete cell-by-cell analysis of the effects of SGLT2 inhibitors on the kidneys of patients with youth onset type 2 diabetes.
Project description:We aimed to predict obesity risk with genetic data, specifically, obesity-associated gene expression profiles. Genetic risk score was computed. The genetic risk score was significantly correlated with BMI when an optimization algorithm was used. Linear regression and built support vector machine models predicted obesity risk using gene expression profiles and the genetic risk score with a new mathematical method.
Project description:Reliable non-invasive tools to diagnose at risk metabolic dysfunction-associated steatohepatitis (MASH) are urgently needed to improve management. We developed a risk stratification score incorporating proteomics-derived serum markers with clinical variables to identify high risk MASH patients (NAFLD Activity Score (NAS) >4 and fibrosis score >2). In this three-phase proteomic study of biopsy-proven metabolic dysfunction-associated steatotic fatty liver disease (MASLD), we first developed a multi-protein predictor for discriminating NAS>4 based on SOMAscan proteomics quantifying 1,305 serum proteins from 57 US patients. Four key predictor proteins were verified by ELISA in the expanded US cohort (N=168), and enhanced by adding clinical variables to create the 9-feature MASH Dx Score which predicted MASH and also high risk MASH (F2+). The MASH Dx Score was validated in two independent, external cohorts from Germany (N=139) and Brazil (N=177). The discovery phase identified a 6-protein classifier that achieved an AUC of 0.93 for identifying MASH. Significant elevation of four proteins (THBS2, GDF15, SELE, IGFBP7) was verified by ELISA in the expanded discovery and independently in the two external cohorts. MASH Dx Score incorporated these proteins with established MASH risk factors (age, BMI, ALT, diabetes, hypertension) to achieve good discrimination between MASH and MASLD without MASH (AUC:0.87- discovery; 0.83- pooled external validation cohorts), with similar performance when evaluating high risk MASH F2-4 (vs. MASH F0-1 and MASLD without MASH). The MASH Dx Score offers the first reliable non-invasive approach combining novel, biologically plausible ELISA-based fibrosis markers and clinical parameters to detect high risk MASH in patient cohorts from the US, Brasil and Europe.
Project description:To evaluate functional consequences of insulin-deficient diabetes mellitus for the liver, we used a genetically engineered pig model of mutant INS gene induced diabetes of youth (MIDY). Liver samples of MIDY pigs and wild-type (WT) littermate controls were analyzed by label-free proteomics to reveal pathways and key drivers significantly affected by chronic insulin deficiency and hyperglycemia.
Project description:To evaluate functional consequences of insulin-deficient diabetes mellitus for adipose tissue, we used a genetically engineered pig model of mutant INS gene induced diabetes of youth (MIDY). Adipose tissue samples of MIDY pigs and wild-type (WT) littermate controls were analyzed by label-free proteomics to reveal pathways and key drivers significantly affected by chronic insulin deficiency and hyperglycemia.
Project description:To gain insight into the relationship between circulating monocytes and cardiovascular risk (CV) progression in patients with type 2 diabetes (T2D), we collected blood monocytes (CD14 positive selection) from 92 people with type 2 diabetes and coronary artery calcium score (CAC-score). Gene expression profiles of circulating monocytes were assessed by RNA sequencing.