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| Renata Pasqualini, PhD
Research Interests:
Angiogenesis inhibitors, pathologic neovascularization, bacteriophage, biological tumor markers |
Our research is aimed at targeting blood vessels for delivery of diagnostic and therapeutic agents by using probes that can bind to specific areas in select vascular beds. Every normal or diseased organ appears to display a unique signature or address on its blood vessels that can serve as a target for selected peptides. Vascular targeting makes it possible to guide toxic drugs, genes, or imaging agents to tumors while sparing normal tissues. We have demonstrated that this approach is an effective means of delivering anticancer drugs or peptides in the treatment of cancer in mice. We have also developed complementary methods of assessing the distribution of peptides guided to specific vasculature, tissues, and target cells.
We have identified small peptides that can target the lining of normal organs or tumor vessels but not normal vessels. These peptides were isolated from a large collection of peptides that are present on the surface of small, virus-like particles known as phages. The phages are injected into the blood, and those that bind to specific blood vessels are isolated. This technology, called in vivo phage display, is now being used to identify the unique molecular addresses of vessels in human vasculature. In another application, phages are being used in blood samples to identify novel tumor markers for the production of anticancer vaccines customized for individual cancer patients.
The potential range of applications for phage-display random peptide libraries is quite broad, and in the past decade, considerable progress has been made in the development of screening methods in which the peptide libraries are used to isolate ligands. The research in our laboratory focuses on exploring the heterogeneity of blood vessels through this technology in order to further our understanding of tumor endothelium specificity and to define the role of endothelial cell markers in angiogenesis and metastasis.
Selected Publications
Kolonin MG, Pasqualini R, Arap W. Teratogenicity induced by targeting a placental immunoglobulin transporter. Proc Natl Acad Sci USA 99:13055-13060, 2002
Arap W, Kolonin MG, Trepel M, Lahdenranta J, Cardo-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 KA, Logothetis CJ, Pasqualini R. Steps toward mapping the human vasculature by phage display. Nat Med 8:121-127, 2002
Giordano RJ, Cardo-Vila M, Lahdenranta J, Pasqualini R, Arap W. Biopanning and rapid analysis of selective interactive ligands. Nat Med 7:1249-1253, 2001
Kolonin M, Pasqualini R, Arap W. Molecular addresses in blood vessels as targets for therapy. Curr Opin Chem Biol 5:308-313, 2001
Trepel M, Grifman M, Weitzman M, Pasqualini R. Molecular adaptors for vascular-targeted adenoviral gene delivery. Hum Gene Ther 11:1971-1981, 2000
Additional Information:
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