E. Helene Sage, PhD
Title:
Member
Email Address:
Phone Number:
206-341-1311
Background
Dr. Sage received her AB degree, magna cum laude and with distinction in Biochemistry, from Mount Holyoke College. She received her PhD in Biochemistry from The University of Utah in 1977. Postdoctoral studies in the Department of Biochemistry at the University of Washington were completed in 1980, and Dr. Sage joined the faculty of the Department of Biological Structure, University of Washington, in 1982. She was promoted to Full Professor in 1990, and initiated the Division of Vascular Biology at the Hope Heart Institute in 1999. Since 2004, Dr. Sage has been a member of the Benaroya Research Institute and retains an Affiliate Professorship in the Department of Biological Structure at the University.
Areas of Research
Projects in Dr. Sage's laboratory are focused on the role of secreted proteins in the regulation of cell behavior. The lab has contributed extensively to the field of extracellular matrix, including the collagens (their structure and function) and the matricellular proteins (such as SPARC, hevin, and thrombospondin). A combinatorial approach involving cell biology, models of human disease, and protein chemistry has produced insights into the regulation of cancers, would healing, and developmental processes by these various proteins.
Selected Publications
Sage, H., R.B. Vernon, S.E. Funk, E.A. Everitt, and J. Angello 1989 SPARC, a Secreted Protein Associated with Cellular Proliferation, Inhibits Cell Spreading In Vitro and Exhibits Ca+2-dependent Binding to the Extracellular Matrix. J. Cell Biol. 109:341-356.
Lane, T.F., and E.H. Sage 1990 Functional Mapping of SPARC: Peptides from Two Distinct Ca++-binding Sites Modulate Cell Shape. J. Cell Biol. 111:3065-3076.
Fouser, L., L. Iruela-Arispe, P. Bornstein and E.H. Sage 1991 Transcriptional Activity of the ?1(I) Collagen Promoter is Correlated with the Formation of Capillary-like Structures by Endothelial Cells in vitro. J. Biol. Chem. 266:18345-18351.
Raines, E.W., T.F. Lane, M.-L. Iruela-Arispe, R. Ross, and E.H. Sage 1992 The Extracellular Glycoprotein SPARC Interacts with Platelet-derived Growth Factor (PDGF)-AB and -BB and Inhibits the Binding of PDGF to its Receptors. Proc. Natl. Acad. Sci. USA 89:1281-1285.
Goldblum, S.E., X. Ding, S.E. Funk, and E.H. Sage 1994 SPARC (Secreted Protein Acidic and Rich in Cysteine) Regulates Endothelial Cell Shape and Barrier Function. Proc. Nat. Acad. Sci. USA 91:3448-3452.
Lane, T.F., M.L. Iruela-Arispe, R.S. Johnson, and E.H. Sage 1994 SPARC is a Source of Copper-binding Peptides That Stimulate Angiogenesis. J. Cell Biol. 125:929-943.
O’Reilly, M.S., L. Holmgren, Y. Shing, C. Chen, R.A. Rosenthal, M. Moses, W.S. Lane, Y. Cao, E.H. Sage, and J. Folkman 1994 Angiostatin: A Novel Angiogenesis Inhibitor that Mediates the Suppression of Metastases by a Lewis Lung Carcinoma. Cell 79:315-328 (Cover).
Iruela-Arispe, M.-L., T.F. Lane, D. Redmond, M. Reilly, R. Bolender, T.J. Kavanagh, and E.H. Sage 1995 Expression of SPARC During Development of the Chicken Chorioallantoic Membrane: Evidence For Regulated Proteolysis In Vivo. Molec. Biol. Cell 6:327-343.
Vernon, R.B., and E.H. Sage 1995 Between Molecules and Morphology: Extracellular Matrix and the Creation of Vascular Form. Am. J. Pathol. 147:873-883.
Iruela-Arispe, M.-L., P. Porter, P. Bornstein, and E.H. Sage 1996 Thrombospondin 1, an Inhibitor of Angiogenesis, is Regulated by Progesterone in the Human Endometrium. J. Clin. Invest. 98:403-412.
Francki, A., A.D. Bradshaw, J.A. Bassuk, C.C. Howe, W.G. Couser and E.H. Sage 1999 SPARC Regulates the Expression of Collagen Type I and Transforming Growth Factor-?1 in Mesangial Cells. J. Biol. Chem. 274:32145-32152.
Brekken, R.A., P. Puolakkainen, D.C. Graves, G. Workman, S.R. Lubkin, and E.H. Sage 2003 Enhanced Growth of Tumors in SPARC-null Mice is Associated with Changes in the ECM. J. Clin. Invest. 111:487-495.
Bradshaw, A.D., D.C. Graves, K. Motamed, and E.H. Sage 2003 SPARC-null Mice Exhibit Increased Adiposity Without Significant Differences in Overall Body Weight. Proc. Nat. Acad. Sci. USA 100:6045-6050.
Sage E.H., M. Reed, S.E. Funk, T. Truong, M. Steadele, P. Puolakkainen, D.H. Maurice, and J. Bassuk 2003 Cleavage of the Matricellular Protein SPARC by Matrix Metalloproteinase 3 Produces Polypeptides that Influence Angiogenesis. J. Biol. Chem. 278:37849-37857.
Barker, T.H., P. Framson, P. Puolakkainen, M. Reed, S.E. Funk, and E.H. Sage 2005 Matricellular Homologs in the Foreign Body Response: Hevin Suppresses Inflammation, but Hevin and SPARC together Diminish Angiogenesis. Am. J. Pathol. 166:923-933.
Barker, T.H., G. Baneyx, M. Cardó-Vila, G.A. Workman, M. Weaver, P.M. Menon, S. Dedhar, S.A. Rempel, W. Arap, R. Pasqualini, V. Vogel, and E.H. Sage 2005 SPARC Regulates Extracellular Matrix Organization through its Modulation of Integrin-linked Kinase Activity. J. Biol. Chem. 43:36483-36493.
Nozaki, M., E. Sakurai, B.J. Raisler, J.Z. Baffi, J. Witta, Y. Ogura, R.A. Brekken, E.H. Sage, B.K. Ambati, and J. Ambati 2006 Loss of SPARC-mediated VEGFR-1 Suppression Post Injury Reveals a Novel Antiangiogenic Activity of VEGF-A. J. Clin. Invest. 116:422-429. (Cited in the Faculty of 1000/Biology)
Kzhyshkowska, J., G. Workman, M. Cardó-Vila, W. Arap, R. Pasqualini, A. Gratchev, L. Krusell, S. Goerdt, and E.H. Sage 2006 Novel Function of Alternatively Activated Macrophages: Stabilin-1-Mediated Clearance of SPARC. J. Immunol. 176:5825-5832.
Sullivan, M.M., T.H. Barker, S.E. Funk, A. Karchin, N.S. Seo, M. Höök, J. Sanders, B. Starcher, T.N. Wight, P. Puolakkainen, and E.H. Sage 2006 Matricellular Hevin Regulates Decorin Production and Collagen Assembly. J. Biol. Chem. 281:27621-27632.
Bornstein, P. and H. Sage 1980 Structurally Distinct Collagen Types. Ann. Rev. Biochem. 49:957-1003 (ISI Citation Classic).
Sage, E.H. 1997 Pieces of Eight: Bioactive Fragments of Extracellular Proteins as Regulators of Angiogenesis. Trends Cell Biol. 7:182-186.
Sage, E.H. 1997 Terms of Attachment: SPARC and Tumorigenesis - News & Views. Nat. Med. 3:144-146.
Bornstein, P. and E.H. Sage 2002 Matricellular Proteins: Extracellular Modulators of Cell Function. Curr. Opin. Cell Biol. 14:608-616.