Project description:study of diphenhydramine in blood and skin - untargeted mass spectrometry analysis [doi:10.25345/C5SJ2X] - reupload for summer school
Project description:Background Vaccinia virus (VACV) infection induces prominent changes in host cell metabolism. Little is known about the global metabolic reprogramming that takes place in the whole tissue during viral infection. Here, we performed an unbiased longitudinal metabolomics study in VACV-infected mice to investigate metabolic changes in the tissue during infection. We assessed metabolites in homogenized skin over time in the presence or absence of antigen-specific T cells using untargeted mass spectrometry. VACV infection induced several significant metabolic changes, including in the levels of nucleic acid metabolites (reflecting the impact of viral replication on the skin metabolome). Furthermore, monocyte- and antiviral T cell-produced metabolites, including itaconic acid, glutamine, and glutathione, were significantly increased following infection, highlighting the immune response’s contribution to the global skin metabolome. Additional RNA-Seq of infected skin tissue recapitulated transcriptional changes identified via metabolomics. Overall, our study reveals the metabolic balance of viral replication and the antiviral immune response in the skin and identifies metabolic pathways that could contribute to cutaneous poxvirus control in vivo.
Project description:Matrix Selection for the Visualization of Small Molecules and Lipids in Brain Tumors Using Untargeted MALDI-TOF Mass Spectrometry Imaging
Project description:Comparison of DNA methylation levels of chromosome 18 between placentas and blood cells of pregnant women Extracted DNA from 5 cases of placental tissues and 5 cases of maternal blood cell was subjected to MeDIP (methylated DNA immunoprecipitation) and hybridized to Affymetrix GeneChip® Human Tiling 2.0R Array sets. A control without immunoprecipitation (IP) was also processed in parallel with the immunoprecipitated DNA samples. The results were validated with bisulfite sequencing and mass spectrometry-based analysis
Project description:By utilizing proteomic and transcriptomic analysis coupled with untargeted polar and non-polar metabolite analysis by liquid chromatography/mass spectrometry, we identified a specific metabolic program elicited by c-MET inhibition. Interference with c-MET drives oxidative metabolism by increasing fatty acid oxidation (FAO) and glucose anaplerosis, which was orchestrated by the master-regulator, PGC1α. Based on a drug screen, we further found that the mitochondrial matrix chaperone inhibitor, gamitrinib, along with c-MET inhibition causes synergistic cell death, which was mechanistically related to the ability of gamitrinib to suppress oxidative metabolism. In alignment with these findings, FAO inhibitor, etomoxir, enhanced the anti-proliferative effects of c-MET inhibition as well. Both combination therapies were active in vivo, suggesting two novel potential combination therapies, involving c-MET inhibitors.
Project description:Markers of biological ageing have potential utility in primary care and public health. We developed a model of age based on untargeted metabolic profiling across multiple platforms, including nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry in urine and serum, within a large sample (N=2,239) from the UK Airwave cohort. We validated a subset of model predictors in a Finnish cohort including repeat measurements from 2,144 individuals. DNA methylation age was assessed for 1,110 participants using the Infinium HumanMethylation EPIC BeadChip. We investigated the determinants of accelerated ageing, including lifestyle and psychological risk factors for premature mortality. The metabolomic age model was well correlated with chronological age (mean r=0.86 across independent test sets). Increased metabolomic age acceleration (mAA) was associated after false discovery rate (FDR) correction with overweight/obesity, diabetes, heavy alcohol use and depression. DNA methylation age acceleration measures were uncorrelated with mAA. Increased DNA methylation phenotypic age acceleration (N = 1,110) was associated after FDR correction with heavy alcohol use, hypertension and low income. In conclusion, metabolomics is a promising approach for the assessment of biological age and appears complementary to established epigenetic clocks.