Wadih Arap, M.D., Ph.D. 1983, University of Sao Paulo; Ph.D., 1996, Stanford University UT M. D. Anderson Cancer Center Genitourinary Medical Oncology and Cancer Biology Contact Information Biographical Sketch

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.

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Arap W, Kolonin MG, Trepel M, Lahdenranta J, Cardó-Vila M, Giordano RJ, Mintz PJ, Ardelt PU, Yao, VJ, Vidal CI, Chen L, Flamm A, Valtanen H, Weavind LM, Hicks ME, Pollock RE, Botz GH, Bucana CD, Koivunen E, Cahill D, Troncoso P, Baggerly KA, Pentz RD, Do K-A, Logothetis CJ, Pasqualini R. Steps toward mapping the human vasculature by phage display. Nat Med 8:121-7, 2002. (Editorials: Science, by Jennifer Couzin; Cancer Cell, by Judah Folkman; Nature Drug Discovery Reviews, by Melanie Brazil, Pharmacogen J, by Phillip Thorpe; Hastings Center Report; Nat Med). (Featured in the Cover)

Cardó-Vila M, Arap W, Pasqualini R. av b5 Integrin-Dependent programmed cell death triggered by a peptide mimic of Annexin V. Mol Cell 11:1151-62, 2003.

Mintz P, Kim J, Do KA, Wang X, Zinner RG, Cristofanilli M, Arap MA, Hong WK, Troncoso P, Logothetis CJ, Pasqualini R, Arap W. Fingerprinting the circulating repertoire of antibodies from cancer patients. Nat Biotechnol 21:57-63, 2003. (Editorial: Nat Biotechnol, by Sam Hanash, 21:37-38, 2003. (Featured in the Cover)

Arap MA, Lahdenranta J, Mintz PJ, Hajitou A, Sarkis AS, Arap W, Pasqualini R. Cell surface expression of the stress response chaperone GRP78 enables tumor targeting by circulating ligands. Cancer Cell 6:275-284, 2004. (Editorials: Science and Nat Med, 2004).

Kolonin MG, Saha PK, Chan L, Pasqualini R, Arap, W. Reversal of obesity by targeted ablation of adipose tissue. Nat Med 10: 625-32, 2004. (Editorials, Science, Nature, Nature Med, Nature Reviews)

Marchió S, Lahdenranta J, Schlingemann RO, Valdembri D, Wesseling P, Arap MA, Hajitou A, Ozawa MG, Trepel M, Giordano RJ, Nanus DM, Dijkman HBPM, Oosterwijk E, Sidman RL, Cooper MD, Bussolino F, Pasqualini R, Arap W. Aminopeptidase A is a functional target in angiogenic blood vessels. Cancer Cell 5:151-62, 2004.

Program Affiliation:
Program in Virology and Gene Therapy
Vascular Biology