The offeror seeks to apply state-of-the-art methods and to develop new approaches andtechniques to investigate a biological process of broad interest to heart, lung and blooddiseases: adaptation to ischemia/hypoxia. Adaptive changes to hypoxia and ischemia areimportant physiologically and become even more prominent in pathological states. Becausehypoxia and ischemia trigger immediate responses in the affected tissues, post-translationalmodification of the proteome will dominate the initial response (whether or not longer-termchanges in gene expression also occur). Detailed characterization of the normal and diseasedproteomes in response to ischemia/hypoxia over time is a necessary step in understanding theadaptive mechanisms. The goal will be to eventually obtain 'disease protein fingerprints' ofnumerous ischemic/hypoxic disorders, which may then provide a unified picture of thepathogenesis - the unique features in, and commonalities among, the various stages of injuryand tissue types. State-of-the-art and innovative methods, coupled with equally state-of-the-artand innovative biology, form the cornerstone of the Hopkins proposal. The central philosophy ofour Center is as follows: compelling biological questions will drive innovation in technologies ofprotein chemistry, instrumentation and data analysis. In turn, the application of innovativetechnologies will revolutionize our understanding of the biology of ischemia/hypoxia.
