Metabolomics and Proteomics
The metabolomics team at MCTP is actively working on the development of a new multiplex metabolite panel for the early detection of prostate cancer. This new testing platform would enhance the diagnostic specificity for progressive disease over conventional PSA testing currently available in the clinics. Changes in metabolites that occur during the development of cancer, particularly changes in amino acid metabolism, may be effective biomarkers of disease progression. Rather than focusing on individual amino acids as biomarkers, a group of key amino acids as a whole are being tested for their diagnostic power. Early studies show promising results and implicate the fatty acid metabolic pathway in prostate cancer progression. We hope to develop candidate fatty acid metabolites for a multiplex panel of diagnostic/prognostic metabolomic biomarkers to differentiate aggressive prostate cancer much more accurately at an early stage than conventional PSA testing. Similar to the PCA3 testing developed at MCTP and currently in use, this will also be a non-invasive urine-based test.
We are also focusing on choline metabolites to determine whether increased oxidation and/or phosphorylation pathways of choline are responsible for the increase in 11C-choline uptake associated with aggressive prostate cancer. In addition, employing LC-MS- and GC-MS-based approaches, we are undertaking a comprehensive steroid profiling (including androgens, corticosteroids, progestogens, estrogens, estrogen metabolites, estrogen conjugates, and estrogen-DNA adducts) as well as exogenous steroid derivatives to determine if there is differential expression in these compounds in prostate cancer.
We are also engaged in metabolomics studies in collaborations with other labs across the UM campus. We are working with Dr. Ramamoorthy, Department of Chemistry utilizing NMR-based metabolomics in combination with gas chromatography/liquid chromatography-mass spectrometry (GC/LC-MS) techniques to develop a multiplex panel for the detection of clinically localized PCa (J Magn Reson. 2013 Jan;226:93-9). NMR in combination with mass spectrometry-based metabolomic profiling are being used to study head and neck cancers (with Dr. Kapila, School of Dentistry, J Proteome Res. 2011 Nov 4;10(11):5232-41) as well as bladder cancer (with Dr. Lee, Department of Urology and Dr. Ramamoorthy, Department of Chemistry, J Proteome Res. 2013 Jul 5;12(7):3519-28).
The MCTP Proteomics Facility provides assistance to researchers in the identification, characterization and quantitation of proteins. Experiments ranging from simple protein discovery to identification of post-translational modifications to large scale relative quantitation can be performed using our state-of-the art instrumentation and software. We provide full range of services, starting with assistance in sample preparation, mass spectrometric analysis, interpretation of the results and statistical analysis.
Our main instrument is ThermoScientific LTQ Velos Pro linear ion trap mass spectrometer coupled to Proxeon nanoLC system. We utilize several software for the analysis of the data, including MASCOT and X!Tandem (for initial search), TPP (for data validation and filtering) and QSPEC (for statistical analysis). We also create on-demand scripts for specific tasks.