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Wadih Arap, M.D., Ph.D. 1983, University of Sao Paulo; Ph.D., 1996, Stanford University The University of Texas M. D. Anderson Cancer Center |
Research Interests:
Proteomics can be defined as the systematic analysis of the proteins in biological samples that aims to document the overall distribution of proteins in cells, identify and characterize individual proteins of interest, and ultimately to elucidate their relationships and functional roles. Vascular proteomics is the molecular phenotyping of cells forming blood vessels at the protein-protein interaction level. We are developing integrated, combinatorial library platform technologies whose goal is to enable the identification, validation, and prioritization of molecular targets in human blood vessels. Expanding our understanding of this complex system will lead to insights into the biology of the tumor circulatory microenvironment, changes in blood vessels during tumor progression, and the localization of novel markers in cancer and in other diseases with an angiogenesis component. The vascular endothelium expresses differential receptors depending on the functional state and tissue localization of its lining cells. We have developed a method to functionally characterize this receptor heterogeneity with phage display random peptide libraries. Using this technology, we have isolated several peptide ligands that home to tissue-specific endothelial cell receptors following intravenous administration. Such peptide ligands can be used to target therapeutic compounds, genes, or imaging agents to endothelial cells in vitro and in vivo. Recent advances in the field include identification of endothelial receptors expressed differentially in normal and pathological conditions and the isolation of peptides or antibody ligands to such receptors in in vitro assays, in animal models, and in patients. These milestones, which extend the “functional map” of the vasculature, should lead to mechanistic insights into diseases that exhibit distinct vascular characteristics such as cancer, obesity, and inflammation.
Program Affiliations:
Program in Virology and
Gene Therapy
Vascular Biology