Matthew Springer, PhD
Profile
Research interests include cell therapy and gene therapy approaches to the study of cardiovascular disease, with the goals of exploring potential treatments and understanding underlying mechanisms involved in angiogenesis, vascular function, and treatments for myocardial infarction. Dr. Matthew L. Springer received his BA from the University of California, Berkeley in 1985 and his Ph.D. from Stanford University in 1992. He did postdoctoral research at Stanford and continued his research there as a senior scientist until joining the UCSF faculty in 2003, where he is currently one of two non-clinicians on the faculty of the Division of Cardiology. The close juxtaposition of his basic research background with the clinical cardiologists in the Division has resulted in an active translational research program. Dr. Springer's research interests include cell therapy and gene therapy approaches to studying cardiovascular disease, with the goals of exploring potential treatments and understanding underlying mechanisms involved in angiogenesis, vascular function, and treatments for myocardial infarction. The laboratory is studying differential responses of cardiac and skeletal muscle to angiogenic gene therapy in mice, focusing on effects of VEGF and pleiotrophin on the vasculature. Further interests center in the therapeutic effects of bone marrow cell implantation into the heart after myocardial infarction, using an ultrasound-guided injection approach that they have developed in collaboration with the Yeghiazarians lab, with a special emphasis on the therapeutic implications of the age and cardiac disease status of the cell donor. Similarly, the lab is studying the effects of age and disease on circulating angiogenic cells (sometimes called endothelial progenitor cells), with a focus on the roles of endothelial nitric oxide synthase and nitric oxide in the function of these cells. Lastly, they have developed a rat model of endothelium-dependent flow-mediated vasodilation, and are using it to examine mechanisms underlying vascular reactivity and how they are affected by cigarette smoke exposure and dietary flavanols.
University of California, Berkeley, B.A., 1981-1985, Molecular Biology
Stanford University, Ph.D., 1985-1991, Biological Sciences
Stanford University, (postdoctoral), 1991-1993, Cell Biology/Biochemistry
Stanford University, (postdoctoral), 1993-1997, Molecular Pharmacology
Selected Publications
Springer, M.L., Chen, A.S., Kraft, P.E., Bednarski, M., and Blau, H.M. (1998). VEGF gene delivery to muscle: Potential role for vasculogenesis. Mol. Cell 2:549-558.
Springer, M.L., Hortelano, G., Bouley, D., Wong, J., Kraft, P.E., and Blau, H.M. (2000). Induction of angiogenesis by implantation of encapsulated primary myoblasts expressing vascular endothelial growth factor. J. Gene Med. 2:279-288.
Lee, R.J., Springer, M.L., Blanco-Bose, W.E., Shaw, R., Ursell, P.C., and Blau, H.M. (2000). VEGF gene delivery to myocardium: Deleterious effects of unregulated expression. Circulation 102:898-901.
Springer, M.L., Ozawa, C.R., Banfi, A., Kraft, P.E., Ip, T.K., Brazelton, T.R., and Blau, H.M. (2003). Localized arteriole formation adjacent to sites of implantation of myoblasts expressing VEGF. Mol. Ther., 7:441-449.
Ozawa, C.R., Banfi, A., Glazer, N., Thurston, G., Springer, M.L., Kraft, P.E., McDonald, D.M., and Blau, H.M. (2004). Microenvironmental VEGF concentration, not total dose, determines a threshold between normal and aberrant angiogenesis. J. Clin. Invest. 113: 516-527.
Springer, M.L., Sievers, R.E., Viswanathan, M., Yee, M.S., Foster, E., Grossman, W., and Yeghiazarians, Y. (2005). Closed-chest cell injections into mouse myocardium guided by high-resolution echocardiography. Amer. J. Physiol. Heart Circ. Physiol., 289:H1307-H1314.
Takagawa, J., Zhang, Y., Sievers, R.E., Kapasi, N.K., Wong, M.L., Wang, Y., Yeghiazarians, Y., Lee, R.J., Grossman, W., and Springer, M.L. (2007). Myocardial infarct size measurement in the mouse chronic infarction model: Comparison of area- and length-based approaches. J. Appl. Physiol. 102:2104-2111.
Springer, M.L., Banfi, A., Ye, J., von Degenfeld, G., Kraft, P.E., Saini, S.A., Kapasi, N.K., and Blau, H.M. (2007). Localization of vascular response to VEGF is not dependent on heparin binding. FASEB J. 21:2074-2085.
Heiss, C., Wong, M.L., Block, V.I., Lao, D., Real, W.M., Yeghiazarians, Y., Lee, R.J., and Springer, M.L. (2008). Pleiotrophin induces nitric oxide dependent migration of endothelial progenitor cells. J. Cell. Physiol. 215:366-373.
Heiss, C., Sievers, R.E., Amabile, N., Momma, T.Y., Chen, Q., Natarajan, S., Yeghiazarians, Y., and Springer, M.L. (2008). In vivo measurement of flow-mediated vasodilation in living rats using high resolution ultrasound. Amer. J. Physiol. Heart Circ. Physiol. 294:H1086-H1093.
Heiss, C., Amabile, N., Lee, A.C., Real, W.M., Schick, S., Lao, D., Wong, M.L., Jahn, S., Angeli, F.S., Minasi, P., Springer, M.L., Hammond, S.K., Glantz, S.A., Grossman, W., Balmes, J.R., and Yeghiazarians, Y. (2008). Second hand smoke causes acute vascular injury, and mobilization of dysfunctional endothelial progenitor cells. J. Am. Coll. Cardiol. 51:1760-1771.
Yeghiazarians, Y., Zhang, Y., Prasad, M., Shih, H., Saini, S.A., Takagawa, J., Sievers, R.E., Wong, M.L., Kapasi, N.K., Mirsky, R., Koskenvuo, J., Minasi, P., Ye, J.,Viswanathan, M.N., Angeli, F.S., Boyle A.J., Springer, M.L., and Grossman, W. (2009). Injection of bone marrow cell extract into infarcted hearts results in functional improvement comparable to intact cell therapy. Mol. Ther.17:1250-1256.
Heiss, C., Jahn, S., Taylor, M., Real, W.M., Angeli, F., Wong, M.L., Amabile, N., Prasad, M., Rassaf, T., Ottaviani, J.I., Mihardja, S., Keen, C.L., Springer, M.L., Boyle, A.,Grossman, W., Glantz, S.A., Schroeter, H., and Yeghiazarians, Y. (2010). Improvement of endothelial function with dietary flavanols is associated with mobilization of circulating angiogenic cells in patients with coronary artery disease. J. Am. Coll. Cardiol. 56:218-224
Heiss, C., Schanz, A., Amabile, N., Jahn, S., Chen, Q., Wong, M.L., Rassaf, T., Heinen, Y., Cortese-Krott, M., Grossman, W., Yeghiazarians, Y., and Springer, M.L. (in press). NO-synthase expression and functional response to NO are both important modulators of circulating angiogenic cell response to angiogenic stimuli. Arterioscler. Thromb. Vasc. Biol. 30:2212-2218.
Zhang, Y., Sievers, R.E., Prasad, M., Mirsky, R., Shih, H., Wong, M.L., Angeli, F.S., Ye, J., Takagawa, J., Koskenvuo, J.W., Springer, M.L., Grossman, W., Boyle, A.J., and Yeghiazarians, Y. (in press). Timing of bone marrow cell therapy is more important than repeated injections after myocardial infarction. Cardiovasc. Pathol., Epub ahead of print, 7/27/10.