Steps toward mapping the human vasculature by phage display

Wadih Arap; Mikhail G. Kolonin; Martin Trepel; Johanna Lahdenranta; Marina Cardó-Vila; Ricardo J. Giordano; Paul J. Mintz; Peter U. Ardelt; Virginia J. Yao; Claudia I. Vidal; Limor Chen; Anne Flamm; Heli Valtanen; Lisa M. Weavind; Marshall E. Hicks; Raphael E. Pollock; Gregory H. Botz; Corazon D. Bucana; Erkki Koivunen; Dolores Cahill; Patricia Troncoso; Keith A. Baggerly; Rebecca D. Pentz; Kim Anh Do; Christopher J. Logothetis; Renata Pasqualini

doi:10.1038/nm0202-121

Steps toward mapping the human vasculature by phage display

Wadih Arap, Mikhail G. Kolonin, Martin Trepel, Johanna Lahdenranta, Marina Cardó-Vila, Ricardo J. Giordano, Paul J. Mintz, Peter U. Ardelt, Virginia J. Yao, Claudia I. Vidal, Limor Chen, Anne Flamm, Heli Valtanen, Lisa M. Weavind, Marshall E. Hicks, Raphael E. Pollock, Gregory H. Botz, Corazon D. Bucana, Erkki Koivunen, Dolores CahillPatricia Troncoso, Keith A. Baggerly, Rebecca D. Pentz, Kim Anh Do, Christopher J. Logothetis, Renata Pasqualini

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517 Scopus citations

Abstract

The molecular diversity of receptors in human blood vessels remains largely unexplored. We developed a selection method in which peptides that home to specific vascular beds are identified after administration of a peptide library. Here we report the first in vivo screening of a peptide library in a patient. We surveyed 47, 160 motifs that localized to different organs. This large-scale screening indicates that the tissue distribution of circulating peptides is nonrandom. High-throughput analysis of the motifs revealed similarities to ligands for differentially expressed cell-surface proteins, and a candidate ligand-receptor pair was validated. These data represent a step toward the construction of a molecular map of human vasculature and may have broad implications for the development of targeted therapies.

Original language	English (US)
Pages (from-to)	121-127
Number of pages	7
Journal	Nature Medicine
Volume	8
Issue number	2
DOIs	https://doi.org/10.1038/nm0202-121
State	Published - Feb 2002
Externally published	Yes

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1038/nm0202-121

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Arap, W., Kolonin, M. G., Trepel, M., Lahdenranta, J., Cardó-Vila, M., Giordano, R. J., Mintz, P. J., Ardelt, P. U., Yao, V. J., Vidal, C. I., Chen, L., Flamm, A., Valtanen, H., Weavind, L. M., Hicks, M. E., Pollock, R. E., Botz, G. H., Bucana, C. D., Koivunen, E., ... Pasqualini, R. (2002). Steps toward mapping the human vasculature by phage display. Nature Medicine, 8(2), 121-127. https://doi.org/10.1038/nm0202-121

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, KA, Logothetis, CJ & Pasqualini, R 2002, 'Steps toward mapping the human vasculature by phage display', Nature Medicine, vol. 8, no. 2, pp. 121-127. https://doi.org/10.1038/nm0202-121

@article{d51f5843d8bb4040b8dc88a369a8dbfb,

title = "Steps toward mapping the human vasculature by phage display",

abstract = "The molecular diversity of receptors in human blood vessels remains largely unexplored. We developed a selection method in which peptides that home to specific vascular beds are identified after administration of a peptide library. Here we report the first in vivo screening of a peptide library in a patient. We surveyed 47, 160 motifs that localized to different organs. This large-scale screening indicates that the tissue distribution of circulating peptides is nonrandom. High-throughput analysis of the motifs revealed similarities to ligands for differentially expressed cell-surface proteins, and a candidate ligand-receptor pair was validated. These data represent a step toward the construction of a molecular map of human vasculature and may have broad implications for the development of targeted therapies.",

author = "Wadih Arap and Kolonin, {Mikhail G.} and Martin Trepel and Johanna Lahdenranta and Marina Card{\'o}-Vila and Giordano, {Ricardo J.} and Mintz, {Paul J.} and Ardelt, {Peter U.} and Yao, {Virginia J.} and Vidal, {Claudia I.} and Limor Chen and Anne Flamm and Heli Valtanen and Weavind, {Lisa M.} and Hicks, {Marshall E.} and Pollock, {Raphael E.} and Botz, {Gregory H.} and Bucana, {Corazon D.} and Erkki Koivunen and Dolores Cahill and Patricia Troncoso and Baggerly, {Keith A.} and Pentz, {Rebecca D.} and Do, {Kim Anh} and Logothetis, {Christopher J.} and Renata Pasqualini",

note = "Funding Information: Acknowledgements We thank R.C. Bast, Jr., R.R. Brentani, W.K. Cavenee, A.C. von Eschenbach, I.J. Fidler, W.K. Hong, D.M. McDonald, J. Mendelsohn and L.A. Zwelling for comments on the manuscript; W.D. Heston for sharing unpublished data; C.L. Cavazos, P.Y. Dieringer, R.G. Nikolova, C.A. Perez, B.H. Restel, C.P. Soto and X. Wang for technical assistance. This work was funded in part by grants from NIH (CA90270 and CA8297601 to R.P., CA90270 and CA9081001 to W.A.) and awards from the Gilson–Longenbaugh Foundation and CaP CURE (to R.P. and W.A.). M.G.K., J.L. and P.J.M. received support from the Susan G. Komen Breast Cancer Foundation, R.J.G. from FAPESP (Brazil), M.C.V. from the Department of Defense, L.C. from the NCCRA and E.K. from the Academy of Finland.",

year = "2002",

month = feb,

doi = "10.1038/nm0202-121",

language = "English (US)",

volume = "8",

pages = "121--127",

journal = "Nature Medicine",

issn = "1078-8956",

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T1 - Steps toward mapping the human vasculature by phage display

AU - Arap, Wadih

AU - Kolonin, Mikhail G.

AU - Trepel, Martin

AU - Lahdenranta, Johanna

AU - Cardó-Vila, Marina

AU - Giordano, Ricardo J.

AU - Mintz, Paul J.

AU - Ardelt, Peter U.

AU - Yao, Virginia J.

AU - Vidal, Claudia I.

AU - Chen, Limor

AU - Flamm, Anne

AU - Valtanen, Heli

AU - Weavind, Lisa M.

AU - Hicks, Marshall E.

AU - Pollock, Raphael E.

AU - Botz, Gregory H.

AU - Bucana, Corazon D.

AU - Koivunen, Erkki

AU - Cahill, Dolores

AU - Troncoso, Patricia

AU - Baggerly, Keith A.

AU - Pentz, Rebecca D.

AU - Do, Kim Anh

AU - Logothetis, Christopher J.

AU - Pasqualini, Renata

N1 - Funding Information: Acknowledgements We thank R.C. Bast, Jr., R.R. Brentani, W.K. Cavenee, A.C. von Eschenbach, I.J. Fidler, W.K. Hong, D.M. McDonald, J. Mendelsohn and L.A. Zwelling for comments on the manuscript; W.D. Heston for sharing unpublished data; C.L. Cavazos, P.Y. Dieringer, R.G. Nikolova, C.A. Perez, B.H. Restel, C.P. Soto and X. Wang for technical assistance. This work was funded in part by grants from NIH (CA90270 and CA8297601 to R.P., CA90270 and CA9081001 to W.A.) and awards from the Gilson–Longenbaugh Foundation and CaP CURE (to R.P. and W.A.). M.G.K., J.L. and P.J.M. received support from the Susan G. Komen Breast Cancer Foundation, R.J.G. from FAPESP (Brazil), M.C.V. from the Department of Defense, L.C. from the NCCRA and E.K. from the Academy of Finland.

PY - 2002/2

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N2 - The molecular diversity of receptors in human blood vessels remains largely unexplored. We developed a selection method in which peptides that home to specific vascular beds are identified after administration of a peptide library. Here we report the first in vivo screening of a peptide library in a patient. We surveyed 47, 160 motifs that localized to different organs. This large-scale screening indicates that the tissue distribution of circulating peptides is nonrandom. High-throughput analysis of the motifs revealed similarities to ligands for differentially expressed cell-surface proteins, and a candidate ligand-receptor pair was validated. These data represent a step toward the construction of a molecular map of human vasculature and may have broad implications for the development of targeted therapies.

AB - The molecular diversity of receptors in human blood vessels remains largely unexplored. We developed a selection method in which peptides that home to specific vascular beds are identified after administration of a peptide library. Here we report the first in vivo screening of a peptide library in a patient. We surveyed 47, 160 motifs that localized to different organs. This large-scale screening indicates that the tissue distribution of circulating peptides is nonrandom. High-throughput analysis of the motifs revealed similarities to ligands for differentially expressed cell-surface proteins, and a candidate ligand-receptor pair was validated. These data represent a step toward the construction of a molecular map of human vasculature and may have broad implications for the development of targeted therapies.

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VL - 8

SP - 121

EP - 127

JO - Nature Medicine

JF - Nature Medicine

IS - 2

ER -

Steps toward mapping the human vasculature by phage display

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