Author: Jordan Vail Price
Publisher:
Published: 2013
Total Pages:
ISBN-13:
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Since the advent of microarray technology in the early 1990's, the development of highly multiplex genomics tools has greatly outpaced the field of proteomics in terms of the generation of useful platforms for basic research and clinical analysis. Yet, to deliver on the great promise of genomics tools that analyze nucleic acids, technologies that permit the analysis of protein-protein interactions on a comparable scale need to be developed. Our group and others have shown that whole-protein and peptide microarrays can provide large amounts of information about the protein interactions that underlie the human immune response in health and disease. Here we describe three novel proteomics microarray platforms and demonstrate that the arrays can be used to gain insight into the antibody-mediated immune response in a spectrum of human diseases. In the first study, we detail the generation of a protein microarray that allows the detection of antibodies that bind to the molecular communication factors of the immune system: cytokines, chemokines, growth factors, and other circulating proteins. Using these arrays, we identified novel targets of autoantibodies in systemic lupus erythematosus, which may delineate a unique subgroup of patients within the spectrum of lupus. In the second study, we describe influenza antigen microarrays that permitted the identification of antibody reactivity to specific influenza hemagglutinin epitopes associated with poor or effective response to the seasonal influenza vaccine. These arrays have potential for development into a clinical diagnostic tool capable of predicting an individual's ability to mount an effective antibody response to vaccination. Finally, we report the development of a silicon-based peptide microarray developed in collaboration with researchers at the Intel Corporation. These "Intel arrays" hold great potential for ultimately enabling highly parallel, real-time measurement of protein-protein interaction with myriad possible downstream applications. The technologies we have developed move the field of multiplex proteomic analysis forward on many fronts, and constitute valuable additions to the proteomics toolkit available to researchers and clinicians. Moreover, our work demonstrates that detailed analysis of protein-protein interaction is required to make more informed models of different states of human health and disease.
