POLLY A. HOFMANN, Ph.D., B.S.

Dean, Faculty Affairs
Professor, Department of Physiology

Office: Ste 1006 910 Madison Building
Tel: (901) 448-2464
phofmann@uthsc.edu

Education

  • PostDoc, University of Wisconsin, Madison WI, Physiology
  • Ph.D., University of Pittsburgh, School of Medicine, Department of Physiology, Pittsburgh, PA, Department of Physiology
  • Ph.D., University of Pittsburgh, Pittsburgh, PA, Physiology
  • B.S., University of Illinois, Champaign, IL, Biology
  • B.S., University of Illinois, Champaign, IL, Biology

Research Interest/Specialty

Research description

On a beat-to-beat basis, force and rate of cardiac contractions can be modified through kinase-dependent phosphorylations and phosphatase-dependent dephosphorylations of myocardial proteins. Short and long-term modification of various myocardial proteins by phosphorylation plays an important role in cardiac survival following ischemia and myocardial function of the hypertrophied heart. In our lab we specifically focus on the molecular mechanisms by which ser/thr phosphatases, such as PP1 and PP2a, are modified and the role of phosphatases in altering myocardial function and survival. Identification of these mechanisms of action under physiologic and pathologic conditions is key to the design of effective clinical therapies.

Research description

On a beat-to-beat basis, force and rate of cardiac contractions can be modified through kinase-dependent phosphorylations and phosphatase-dependent dephosphorylations of myocardial proteins. Short and long-term modification of various myocardial proteins by phosphorylation plays an important role in cardiac survival following ischemia and myocardial function of the hypertrophied heart. In our lab we specifically focus on the molecular mechanisms by which ser/thr phosphatases, such as PP1 and PP2a, are modified and the role of phosphatases in altering myocardial function and survival. Identification of these mechanisms of action under physiologic and pathologic conditions is key to the design of effective clinical therapies.

Publications

  1. Cai, C, Lothstein, L, Morrison, RR, Hofmann, PA. Protection from doxorubicin-induced cardiomyopathy using the modified anthracycline N-benzyladriamycin-14-valerate (AD 198). J Pharmacol Exp Ther, 335 (1), 223-30, 2010.
  2. Hofmann, PA, Israel, M, Koseki, Y, Laskin, J, Gray, J, Janik, A, Sweatman, TW, Lothstein, L. N-Benzyladriamycin-14-valerate (AD 198): a non-cardiotoxic anthracycline that is cardioprotective through PKC-epsilon activation. J Pharmacol Exp Ther, 323 (2), 658-64, 2007.
  3. Morrison, RR, Tan, XL, Ledent, C, Mustafa, SJ, Hofmann, PA. Targeted deletion of A2A adenosine receptors attenuates the protective effects of myocardial postconditioning. Am J Physiol Heart Circ Physiol, 293 (4), H2523-9, 2007.
  4. Blunt, BC, Creek, AT, Henderson, DC, Hofmann, PA. H2O2 activation of HSP25/27 protects desmin from calpain proteolysis in rat ventricular myocytes. Am J Physiol Heart Circ Physiol, 293 (3), H1518-25, 2007.
  5. Zhu, Z, Hofmann, PA, Buolamwini, JK. Cardioprotective effects of novel tetrahydroisoquinoline analogs of nitrobenzylmercaptopurine riboside in an isolated perfused rat heart model of acute myocardial infarction. Am J Physiol Heart Circ Physiol, 292 (6), H2921-6, 2007.
  6. Deshmukh, PA, Blunt, BC, Hofmann, PA. Acute modulation of PP2a and troponin I phosphorylation in ventricular myocytes: studies with a novel PP2a peptide inhibitor. Am J Physiol Heart Circ Physiol, 292 (2), H792-9, 2007.
  7. Rajashree, R, Blunt, BC, Hofmann, PA. Modulation of myosin phosphatase targeting subunit and protein phosphatase 1 in the heart. Am J Physiol Heart Circ Physiol, 289 (4), H1736-43, 2005.
  8. Blunt, BC, Chen, Y, Potter, JD, Hofmann, PA. Modest actomyosin energy conservation increases myocardial postischemic function. Am J Physiol Heart Circ Physiol, 288 (3), H1088-96, 2005.
  9. Liu, Q, Hofmann, PA. Protein phosphatase 2A-mediated cross-talk between p38 MAPK and ERK in apoptosis of cardiac myocytes. Am J Physiol Heart Circ Physiol, 286 (6), H2204-12, 2004.
  10. Chen, Y, Rajashree, R, Liu, Q, Hofmann, P. Acute p38 MAPK activation decreases force development in ventricular myocytes. Am J Physiol Heart Circ Physiol, 285 (6), H2578-86, 2003.
  11. Pyle, WG, Chen, Y, Hofmann, PA. Cardioprotection through a PKC-dependent decrease in myofilament ATPase. Am J Physiol Heart Circ Physiol, 285 (3), H1220-8, 2003.
  12. Liu, Q, Hofmann, PA. Modulation of protein phosphatase 2a by adenosine A1 receptors in cardiomyocytes: role for p38 MAPK. Am J Physiol Heart Circ Physiol, 285 (1), H97-103, 2003.
  13. Grey, EM, Chan, CK, Chen, Y, Hofmann, PA. Age-related functional effects linked to phosphatase activity in ventricular myocytes. Am J Physiol Heart Circ Physiol, 285 (1), H90-6, 2003.
  14. Liu, Q, Hofmann, PA. Antiadrenergic effects of adenosine A(1) receptor-mediated protein phosphatase 2a activation in the heart. Am J Physiol Heart Circ Physiol, 283 (4), H1314-21, 2002.
  15. Rajashree, R, Koster, JC, Markova, KP, Nichols, CG, Hofmann, PA. Contractility and ischemic response of hearts from transgenic mice with altered sarcolemmal K(ATP) channels. Am J Physiol Heart Circ Physiol, 283 (2), H584-90, 2002.
  16. Pyle, WG, Lester, JW, Hofmann, PA. Effects of kappa-opioid receptor activation on myocardium. Am J Physiol Heart Circ Physiol, 281 (2), H669-78, 2001.
  17. Lester, JW, Hofmann, PA. Role for PKC in the adenosine-induced decrease in shortening velocity of rat ventricular myocytes. Am J Physiol Heart Circ Physiol, 279 (6), H2685-93, 2000.
  18. Pyle, WG, Smith, TD, Hofmann, PA. Cardioprotection with kappa-opioid receptor stimulation is associated with a slowing of cross-bridge cycling. Am J Physiol Heart Circ Physiol, 279 (4), H1941-8, 2000.
  19. Redaelli, G, Malhotra, A, Li, B, Li, P, Sonnenblick, EH, Hofmann, PA, Anversa, P. Effects of constitutive overexpression of insulin-like growth factor-1 on the mechanical characteristics and molecular properties of ventricular myocytes. Circ Res, 82 (5), 594-603, 1998.
  20. Rigby, SL, Hofmann, PA, Zhong, J, Adams, HR, Rubin, LJ. Endotoxemia-induced myocardial dysfunction is not associated with changes in myofilament Ca2+ responsiveness. Am J Physiol, 274 (2 Pt 2), H580-90, 1998.
  21. Lester, JW, Gannaway, KF, Reardon, RA, Koon, LD, Hofmann, PA. Effects of adenosine and protein kinase C stimulation on mechanical properties of rat cardiac myocytes. Am J Physiol, 271 (5 Pt 2), H1778-85, 1996.
  22. Dunlap, AW, Thomason, DB, Menon, V, Hofmann, PA. Decreased Ca2+ sensitivity of isometric tension in skinned cardiac myocytes from tail-suspended rats. J Appl Physiol, 80 (5), 1612-7, 1996.
  23. Hofmann, PA, Menon, V, Gannaway, KF. Effects of diabetes on isometric tension as a function of [Ca2+] and pH in rat skinned cardiac myocytes. Am J Physiol, 269 (5 Pt 2), H1656-63, 1995.
  24. Hofmann, PA, Lange, JH. Effects of phosphorylation of troponin I and C protein on isometric tension and velocity of unloaded shortening in skinned single cardiac myocytes from rats. Circ Res, 74 (4), 718-26, 1994.
  25. Hofmann, PA, Miller, WP, Moss, RL. Altered calcium sensitivity of isometric tension in myocyte-sized preparations of porcine postischemic stunned myocardium. Circ Res, 72 (1), 50-6, 1993.
  26. Hofmann, PA, Moss, RL. Effects of calcium on shortening velocity in frog chemically skinned atrial myocytes and in mechanically disrupted ventricular myocardium from rat. Circ Res, 70 (5), 885-92, 1992.
  27. Hofmann, PA, Greaser, ML, Moss, RL. C-protein limits shortening velocity of rabbit skeletal muscle fibres at low levels of Ca2+ activation. J Physiol, 439, 701-15, 1991.
  28. Hofmann, PA, Hartzell, HC, Moss, RL. Alterations in Ca2+ sensitive tension due to partial extraction of C-protein from rat skinned cardiac myocytes and rabbit skeletal muscle fibers. J Gen Physiol, 97 (6), 1141-63, 1991.
  29. Hofmann, PA, Metzger, JM, Greaser, ML, Moss, RL. Effects of partial extraction of light chain 2 on the Ca2+ sensitivities of isometric tension, stiffness, and velocity of shortening in skinned skeletal muscle fibers. J Gen Physiol, 95 (3), 477-98, 1990.
  30. Hofmann, PA, Fuchs, F. Bound calcium and force development in skinned cardiac muscle bundles: effect of sarcomere length. J Mol Cell Cardiol, 20 (8), 667-77, 1988.
  31. Hofmann, PA, Fuchs, F. Evidence for a force-dependent component of calcium binding to cardiac troponin C. Am J Physiol, 253 (4 Pt 1), C541-6, 1987.