The goal of this SBIR application is to demonstrate the feasibility of a global approach to screen for disease specific monoclonal antibodies (mAbs) to low level proteins for the discovery and validation of biomarkers of alcohol-induced liver damage. The technology will utilize a workflow that is essentially the reverse of that followed today, where antigens are first identified and then antibodies generated for potential biomarkers. In the present proposal, plasma proteome of alcohol-induced liver damage patients and a suitable control group will be screened against more than 1000 hybridomas for discriminating antibodies, seeking for at least 10 apparently disease specific discriminating biomarker mAbs. To demonstrate that the mAbs are to low level proteins, the antigens for at least 5 mAbs will be identified by affinity isolation and mass spectrometry. The level of these proteins in blood will also be determined or estimated. The suggested approach represents a novel method for biomarker discovery and validation, offering more than 10-fold greater sensitivity, as well as being 10-fold less expensive and many-fold higher throughput than present day LC/MS based approaches. Once feasibility of the approach has been demonstrated, the methodology will be ready for implementation on individual patient samples. Important to the success of this project is the collaboration of Biosystems International, a startup company with expertise in immunology and assay development, with the Barnett Institute at Northeastern University in Boston, MA, a research center with expertise in chromatography and mass spectrometry. A critical need today is the development of technology that can rapidly and cost effectively deliver disease specific antibodies for low level proteins in blood and that can be used to discover and validate biomarkers for the early detection of alcohol-induced liver damage. The goal of this program is to meet this need, and the reagents generated should be widely utilized for diagnostic purposes.
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