National Heart, Lung, and Blood Institute Proteomics Initiative

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The offeror seeks to apply state-of-the-art methods and to develop new approaches and techniques to investigate a biological process of broad interest to heart, lung and blood diseases: adaptation to ischemia/hypoxia. Adaptive changes to hypoxia and ischemia are important physiologically and become even more prominent in pathological states. Because hypoxia and ischemia trigger immediate responses in the affected tissues, post-translational modification of the proteome will dominate the initial response (whether or not longer-term changes in gene expression also occur). Detailed characterization of the normal and diseased proteomes in response to ischemia/hypoxia over time is a necessary step in understanding the adaptive mechanisms. The goal will be to eventually obtain "disease protein fingerprints" of numerous ischemic/hypoxic disorders, which may then provide a unified picture of the pathogenesis - the unique features in, and commonalities among, the various stages of injury and tissue types. State-of-the-art and innovative methods, coupled with equally state-of-the-art and innovative biology, form the cornerstone of the Hopkins proposal. The central philosophy of our Center is as follows: compelling biological questions will drive innovation in technologies of protein chemistry, instrumentation and data analysis. In turn, the application of innovative technologies will revolutionize our understanding of the biology of ischemia/hypoxia.