Stephen W. Schaffer, Ph.D.

Stephen W. Schaffer, Ph.D.Professor Emeritus
USA Department of Pharmacology

Ph.D.: University of Minnesota
Post-doctoral: University of Pennsylvania 

Research Interests

Dr. Schaffer's laboratory has been studying the effects of diabetes and hypertension on heart function.  In addition to developing a cardio- myopathy, individuals suffering from diabetes or hypertension are at increased risk of ischemic heart disease.   The effects of diabetes are closely tied to changes in cell signaling and cardiac metabolism while the effects of hypertension are related to events mediated by increased preload and afterload.   An important player in both diseases is angiotensin II, which initiates an array of signaling pathways that can kill the cardiomyocyte and adversely affect myocardial function.  Dr. Schaffer's studies have discovered a signaling pathway of angiotensin II in which reactive species generated in the cytosol trigger mitochondrial oxidative stress through a complex series of steps that includes mitochondrial DNA damage.  Dr. Schaffer believes that this pathway contributes to both the development of the diabetic cardiomyopathy and to pressure-mediated ischemic injury.   Of particular interest are the clinical implications of elevated afterload pressure on the ischemic heart.  Dr. Schaffer's work suggests that reductions in blood pressure may serve as an important mechanism of protecting the heart against ischemic injury.

Representative Publications

  1. S.W. Schaffer, B.H. Tan and G.L. Wilson, Development of a cardiomyopathy in a model of noninsulin-dependent diabetes.  Am J Physiol 246, H179-H185 (1985).
  2. S.W. Schaffer, M. Seyed-Mozaffari, C.R. Cutcliff and G.L. Wilson, Postreceptor myocardial metabolic defect in a rat model of noninsulin-dependent diabetes mellitus. Diabetes 35, 593-597 (1986).
  3. S.W. Schaffer, M.S. Mozaffari, M. Artman and G.L. Wilson, Basis for myocardial mechanical defects associated with noninsulin-dependent diabetes.  Am J Physiol 256, E25-E30 (1989).
  4. S.N. Allo and S.W. Schaffer, Defective sarcolemmal phosphorylation associated with noninsulin-dependent diabetes.  Biochim Biophys Acta 1023, 206-212 (1990).
  5. S.N. Allo, T.M. Lincoln, G.L. Wilson, F.J. Green, A.M. Watanabe and S.W. Schaffer, Noninsulin-dependent diabetes induced defects in cardiac cellular calcium regulation.  Am J Physiol 260, C1165-C1171 (1991).
  6. R.S. Kaplan, J.A. Mayor, R. Blackwell, G.L. Wilson and S.W. Schaffer, Functional levels of mitochondrial anion transport proteins in noninsulin-dependent diabetes mellitus. Mol Cell Biochem 107, 79-86 (1991).
  7. S.W. Schaffer, S. Allo, S. Punna and T. White, Defective response to cAMP-dependent protein kinase in noninsulin-dependent diabetic heart. Am J Physiol 261, E369-E376 (1991).
  8. S.W. Schaffer, Cardiomyopathy associated with noninsulin-dependent diabetes. Mol Cell Biochem 107, 1-20 (1991).
  9. S.W. Schaffer and G.L. Wilson, Factors contributing to the insulin resistance and mechanical dysfunction that develops in the hearts of Wistar rats with streptozotocin-induced noninsulin-dependent diabetes, Diabetologia 36, 195-199 (1993).
  10. S.W. Schaffer, B.A. Warner and G.L. Wilson, Effects of chronic glipizide treatment on the noninsulin-dependent diabetic heart, Hormone Metabol Res 25, 348-352 (1993).
  11. Y. Liu, J.D. Thornton, M.V. Cohen, J.M. Downey and S.W. Schaffer, Streptozotocin-induced non-insulin-dependent diabetes protects the heart from infarction, Circulation 88, 1273-1278 (1993).
  12. C. Ballard and S. Schaffer. Stimulation of the Na+/Ca2+ exchanger by phenylephrine, angiotensin II and endothelin 1. J Mol Cell Cardiol 28, 11-17 (1996).
  13. S.W. Schaffer and M. Mozaffari. Abnormal mechanical function in diabetes: relation to myocardial calcium handling. Cor Art Dis 7, 109-115 (1996).
  14. S.W. Schaffer, C. Ballard-Croft, S. Boerth and S.N. Allo.  Mechanisms underlying depressed Na+-Ca2+ exchanger activity in the diabetic heart. Cardiovascular Research 34, 129-136 (1997).
  15. S.W. Schaffer, C. Ballard Croft and V. Solodushko, Cardioprotective effect of chronic hyperglycemia: Effect of hypoxia-induced apoptosis and necrosis. Am J Physiol 278, H1948-H1954 (2000).
  16. M.S. Mozaffari and S.W. Schaffer. Effect of hypertension and hypertension-glucose intolerance on myocardial ischemic injury. Hypertension 42, 1042-1049 (2003).
  17. V. Grishko, V. Pastukh, V. Solodushko, M. Gillespie, J. Azuma and S. Schaffer. Apoptotic cascade initiated by angiotensin II in neonatal cardiomyocytes: role of DNA damage. Am J Physiol, 285/286, H2364-2372 (2003).
  18. T. Krieg, X-M Yang, J.M. Downey, S.W. Schaffer and M.V. Cohen. Augmented taurine release is not the mechanism of ischemic preconditioning's cardioprotection. Amino Acids 26, 263-266 (2004).
  19. V. Pastukh, S. Wu, C. Ricci, M. Mozaffari and S. Schaffer. Reversal of hyperglycemic preconditioning by angiotensin II: role of calcium transport. Am J Physiol 288: H1965-H1975 (2005).
  20. M.S. Mozaffari, C. Patel, C. Ballas and S.W. Schaffer, Effects of excess salt and fat intake on myocardial function and infarct size in rat. Life Sci 78: 1808-1813 (2006).
  21. M.S. Mozaffari, C. Patel and S.W. Schaffer, Mechanisms underlying afterload-induced exacerbation of myocardial infarct size: role of T-type Ca2+ channel. Hypertension 47: 912-919 (2006).
  22. C. Ricci, V. Pastukh, M. Mozaffari and S.W. Schaffer, Insulin withdrawal induces apoptosis via a free radical mediated mechanism. Can J Physiol Pharmacol 85: 455-464 (2007).
  23. C Ricci, C.J. Jong and S.W. Schaffer, Pro-apoptotic and anti-apoptotic effects of hyperglycemia: role of insulin signaling. Can J Physiol Pharmacol 86: 166-172 (2008).
  24. C. Ricci, V. Pastukh, J. Leonard, J. Turrens, G. Wilson, D. Schaffer and S.W. Schaffer. Mitochondrial DNA damage triggers mitochondrial superoxide generation and apoptosis. Am J Physiol 294: C413-C422 (2008).
  25. M.S. Mozaffari and S.W. Schaffer. Effect of pressure overload on cardioprotection of mitochondrial KATP channels and glycogen synthase kinase 3b: interaction with the MPT pore. Am J Hypertens 21: 570-575 (2008).
  26. T. Ito, Y. Kimura, Y. Uozumi, M. Takai, S. Muraoka, T. Matsuda, K. Ueki, M. Yoshiyama, M. Ikawa, M. Okabe, S.W. Schaffer, Y. Fujio and J. Azuma. Taurine deletion caused by knocking out the taurine  transporter gene leads to a cardiomyopathy with cardiac atrophy. J Mol Cell Cardiol 44: 927-937 (2008).
  27. M.S. Mozaffari and S.W. Schaffer. Myocardial ischemic-reperfusion injury in a rat model of metabolic syndrome. Obesity 16: 2253-2258 (2008).
  28. S.W. Schaffer, J. Azuma and M. Mozaffari. Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 87: 91-99 (2009).
  29. S.W. Schaffer and M. Mozaffari, The neonatal STZ model of diabetes. In: Experimental Models of Diabetes, J.H. McNeill (ed), CRC Press, pp. 231-255, Boca Raton, FL (1999).
  30. S.W. Schaffer and M. Mozaffari, Regulation of myocardial phospholipid N-methylation by insulin and diabetes. In: Diabetes and Cardiovascular Disease: Etiology, treatment and outcomes, A. Angel, N Dhalla, G. Pierce, P. Singal (eds), Kluwer Academic/Plenum Publishers, pp. 175-181, New York/Boston/Dordrecht/London/Moscow (2001).
  31. S. Schaffer, J. Azuma, K. Takahashi and M. Mozaffari. Why is taurine cytoprotective? In: Taurine 5: Beginning the 21st Century, J.B. Lombardini, S.W. Schaffer and J. Azuma (eds), Kluwer Plenum Publishers, pp. 307-321, New York/Boston. Dordrecht/London/Moscow (2003).
  32. M.S. Suleiman and S.W. Schaffer.  The apoptotic mitochondrial pathway - modulators, interventions and clinical applications. In: Mitochondria: the dynamic organelleSchaffer SW and Suleiman, MS (eds), Springer Publications, New York pp. 271-290 (2007).
  33. S.W. Schaffer and M.S. Mozaffari. Angiotensin II signaling: cell growth and apoptosis. In: Signal transduction in cardiovascular systems in health and disease. Srivastava A and Srivastava M (eds), Springer Publications, New York, pp 117-137 (2008).

Books Edited

  1. The Effects of Taurine on Excitable Tissues, S.W. Schaffer, S.I. Baskin and J.J. Kocsis (eds.), Spectrum Publications, New York, 1981.
  2. Prostaglandins: Research and Clinical Update, G.L. Longenecker and S.W. Schaffer (eds.), Alpha Editions, Minneapolis, 1985.
  3. Taurine: Nutritional Value and Mechanisms of Action, J.B. Lombardini, S.W. Schaffer and J. Azuma (eds.), Plenum Press, New York, 1992.
  4. Taurine 3: Cellular and Regulatory Mechanisms, S. Schaffer, J.B. Lombardini and R.J. Huxtable (eds.)  Plenum Press, New York/London, 1998.
  5. Taurine 5: Beginning the 21st Century, J.B. Lombardini, S.W. Schaffer and J. Azuma (eds), Kluwer Plenum Publications, New York/Boston/Dordrecht/London/Moscow, 2003.
  6. Mitochondria: the dynamic organelle, S.W. Schaffer and M.S. Suleiman (eds), Springer Publications, New York, 2007
  7. Taurine 7, J. Azuma, S.W. Schaffer and T. Ito (eds.), Springer Publications, New York, 2009.