the Food and Drug Administration announced the development of the Critical Path Initiative in order to address the decreasing numbers of innovative medical products being submitted for approval. The first topic addressed by this report was the pressing need for the development of new biomarkers to improve clinical trials and improve medical therapy. In 2007, the School of Medicine and the Institute for Genome Sciences &Policy at Duke University collaborated to create the Duke Proteomics Core Facility, a shared resource facility with a mission to provide protein characterization resources and expertise in support of the basic and clinical research programs of Duke Investigators. The Proteomics Core Facility was originally designed to provide capabilities for liquid-chromatography-mass spectrometry (LC/MS) based proteomics for protein identification and protein quantitation, including biomarker discovery (open LC/MS/MS) and biomarker verification (targeted LC/MS/MS with multiple reaction monitoring) experiments, and has recently (February 2009) added the capability for multiplexed antibody assays for these biomarker verification studies. The Duke Proteomics Facility came on-line in September 2007, and has successfully served the proteomics needs of 44 Principal Investigators across the School of Medicine. The majority of the projects have been differential expression projects, providing both qualitative and quantitative information on a wide variety of sample types, including cell lines, tissue lysates, protein complexes, and biofluids. Of particular relevance is the success in biomarker discovery experiments in human clinical samples, which has lead to a significant increase in the number of projects submitted for biomarker discovery proteomics. Because of the large number of biomarker discovery/verification samples in the queue in 2009 from projects that have committed funds for their analyses (>1,300 LC/MS analyses), our Facility has reached maximum capacity, with new projects of this type being delayed indefinitely or turned away due to lack of LC/MS instrument time. Therefore, this S10 proposal requests an open 'omic LC/MS system effectively identical to the system we have in place in our facility to support the research projects from NIH-funded investigators described in this proposal. Thus, the focus is on adding capacity to our Facility, with the additional capacity coming from an instrument platform where we have a proven track record of success, one which has demonstrated excellent quantitative reproducibility and sufficient system ruggedness for clinical-scale biomarker studies, as is necessary to achieve the research aims of the studies described in this proposal.
The proposed LC/MS system will significantly increase the capacity of the Duke Proteomics Facility to conduct differential protein expression analyses of biologic materials such as cell and tissue lysates, blood, and other body fluids. The research projects enabled by this proposal aim to advance our understanding of disease areas including oncology, heart disease, liver disease, osteoarthritis, and infectious diseases, and ultimately will improve clinical trials and patient therapies through the discovery and characterization of protein 'biomarkers'of health and disease. This LC/MS system will essentially double the instrument capacity available for such studies at Duke and enable us to leverage the extensive expertise, robust data analysis capabilities, and plethora of important biomedical research opportunities at Duke to the fullest extent.
