Lindsey Miles, PhD
Research Focus
Regulation of the Plasminogen Activation System
Dr. Miles studies how interactions of proteolytic systems (specifically the plasminogen activation system) with cell surfaces modulate cellular function and how cells modulate protease systems via positive feedback mechanisms. Recently, using a proteomics approach and a monocyte progenitor cell line, Dr. Miles identified a novel protein, the plasminogen receptor, Plg-RKT, which has unique properties including a transmembrane topology with a carboxyl terminal lysine exposed on the cell surface in an orientation to bind plasminogen and stimulate plasminogen activation and is colocalized with and physically associates with the urokinase type plasminogen activator receptor (uPAR). Ongoing research employs newly developed reagents including specific function-blocking anti-Plg-RKT antibodies, region specific peptide mimetics, and Plg-RKT protein expression systems to address the role of this new plasminogen receptor in inflammation and cancer progression.
Education
Ph.D., University of California, San Diego,Professional Experience
2013-2017 Professor of Cell and Molecular Biology, Cell and Molecular Biology (CMB), Scripps Research-2012 Associate Professor of Cell Biology, Cell Biology, Scripps Research
Awards & Professional Activities
American Heart Association Special Recognition Award in Thrombosis (2004)American Heart Association, National Thrombosis Study Group;
American Heart Association, Council on Arteriosclerosis, Thrombosis and Vascular Biology, Women's Leadership Committee, Chair;
American Heart Association, Council on Arteriosclerosis, Thrombosis and Vascular Biology Leadership Committee;
American Heart Association Western States Affiliate Research Committee;
American Heart Association Western Consortium, Review Committee 4B, Co-chair;
President, XVIIth International Congress on Fibrinolysis and Proteolysis (2006);
Council Member, International Society for Fibrinolysis and Proteolysis;
Editorial Boards: Frontiers in Bioscience, Thrombosis and Haemostasis
Selected References
For a complete list of publications: http://www.scripps.edu/miles/publications.html
Miles, L.A., Lighvani, S., Baik, N., Parmer, C.M., Khaldoyanidi, S., Mueller, B.M., Parmer, R.J. New insights into the role of Plg-RKT in macrophage recruitment. International Review of Cell & Molecular Biology, In Press, 2013.
Gingles, N.A., Bai H., Miles, L.A., and Parmer, R.J. Peptidergic regulation of plasminogen activator inhibitor-1 gene expression in vivo. Journal of Thrombosis and Haemostasis, 2013 Sep;11(9):1707-15. PMID: 2380003
Miles, L.A. and Parmer, R.J., Plasminogen receptors: The First Quarter Century. Seminars in Thrombosis and Hemostasis. 2013 Jun;39(4):329-37
Miles, L.A., Andronicos, N.M., Chen, E.I., Baik, N., Bai, H., Parmer, C.M., Lighvani, S., Nangia, S., Kiosses, W.B., Kamps, M.P., Yates III, J.R. and Parmer, R.J. Identification of the novel plasminogen receptor, Plg-RKT. In: Proteomics/Book 1: Human Diseases and Protein Functions, ISBN 978-953-307-832-8, Man, T.K. and Flores, R.J.(Ed.), Intech, Chapter 10: 219-238, 2012. Available from: http://www.intechopen.com/articles/show/title/identification-of-the-novel-plasminogen-receptor-plg-rkt
Miles, L.A., Plow, E.F., Waisman, D.M., and Parmer, R.J. Plasminogen Receptors. Journal of Biomedicine and Biotechnology. 2012 2012:130735 Epub 2012 Nov 20. PMID: 23226936
Miles, L.A., Lighvani, S., Baik, N., Andronicos, N., Chen, E.I., Parmer, C.M., Khaldoyanidi, S., Diggs, J., Kiosses, W., Kamps, M.P., Yates, J.R., Parmer, R.J. The plasminogen receptor, Plg-RKT, and macrophage function. Journal of Biomedicine and Biotechnology, 2012 2012:250464 Epub 2012 Oct 14. PMCID: PMC3484331
Felez, J., Jardi, M., Fabregas, P., Parmer, R.J., Miles, L.A. Monoclonal antibodies against receptor-induced binding sites detect cell-bound plasminogen in blood. Blood, 2012 Jul 19;120(3):678-81. PMCID: PMC3401219
Lighvani, S., Baik, N., Diggs, J.E., Khaldoyanidi, S., Parmer, R.J, and Miles, L.A. Regulation of macrophage migration by a novel plasminogen receptor Plg-RKT. Blood, 2011 Nov 17;118(20):5622-30. PMCID: PMC3217361
Bai, H. Baik, N., Kiosses, W.B., Krajewski, S., Miles, L.A., Parmer, R.J. The novel plasminogen receptor, Plg-RKT regulates catecholamine release. J Biol Chem, 2011 Sept 23;286(38):33125-33. PMCID: PMC3190921
Han, J., Baik, N., Kim, K-H, Yang, J-M, Han, G., Gong, Y., Jardi, M., Castellino, F.J., Felez, J., Parmer, R.J. and Miles, L.A. Monoclonal antibodies detect receptor-induced binding sites (RIBS) in Glu-plasminogen. Blood, 2011 Aug 11;118(6):1653-62. PMCID: PMC3156051
Jiang, Q., Gingles, N.A., Olivier, M.A., Miles, L.A., Parmer, R.J. The anti-fibrinolytic SERPIN, plasminogen activator inhibitor 1 (PAI-1), is targeted to and released from catecholamine storage vesicles. Blood, 2011 Jun 30;117(26):7155-62. PMCID: PMC3143556
Miles, L.A. and Parmer, R.J. S100A10: A complex inflammatory role. Blood, 2010 Aug 19;116(7):1022-4. PMID: 20724548
Miles, L.A. and Parmer, R.J. PAI-1: Cardiac friend or foe? Blood, 10:1862-1863, 2010. PMID: 20223930.
Andronicos, N.M., Chen, E.I., Baik, N., Bai, H., Parmer, C.M., Kiosses, W.B., Kamps, M.P., Yates, J.R., III, Parmer, R.J., Miles, L.A. Proteomics-based discovery of a novel, structurally unique, and developmentally regulated plasminogen receptor, Plg-RKT, a major regulator of cell surface plasminogen activation. Blood, 2010 Feb 18;115(7): 1319-30. Plenary Paper. PMCID: PMC2826757