Physiology

MARIUS P. SUMANDEA, Ph.D. Assistant Professor Ph.D. University of Illinois, Chicago, 1999 Office: BBSRB-B249 Tel: (859) 323-6613 Lab: BBSRB – B206, B213 E-mail: mariussumandea@uky.edu

Molecular, cellular and mechanical dynamics of cardiac muscle function

Cardiac muscle contraction and relaxation is the result of integrated activity of highly synchronized and fine-tuned protein-protein interactions. An important challenge in the study of heart muscle function is to understand the significance of alterations at the molecular level (for example, phosphorylation, missense mutations or deletions, proteolysis, oxidation etc.) to integrated biology of contraction and relaxation.

Our laboratory’s primary research focus is on a protein called troponin, which serves as a molecular switch involved in calcium-dependent regulation of cardiac muscle contraction. Troponin is a heterotrimeric complex consisting of a Ca2+-binding protein, troponin C; an actomyosin MgATPase inhibiting protein, troponin I, and a tropomyosin-binding protein, troponin T. Troponin is a “hot spot” for: phosphorylation by various kinases (PKA, PKC, PAK, ROCK, Raf etc.); missense mutations and deletions that are causal in cardiomyopathies; disease-induced proteolysis (caspase 3, caplain etc.) and oxidation - all of which are well correlated with altered cardiac dynamics.

Our long-term goals are: 1) to unravel the molecular mechanisms that modulate cardiac muscle activity under normal and disease states; 2) understand how biochemical signal transduction pathways influence cardiac cell function and 3) develop new approaches for heart failure treatments. To this end, we utilize multidisciplinary approaches that integrate the strength of molecular and cellular biology, microbiology, biochemistry, biophysics and physiology.

Recent publications:

Marius P. Sumandea, Chaojian Wang, Aaron Hinken, Vitalyi O. Rybin, Tomoyoshi Kobayashi, Gail Sievert, Steven J. Feinmark, C. William Balke, R. John Solaro, Susan F. Steinberg, Tyrosine phosphorylation modifies PKCdelta-dependent phosphorylation of cardiac troponin I, J. Biol. Chem, Epub June 12 2008, M802396200

Ye Chen-Izu, Christopher W. Ward, Wayne Stark Jr., Tamas Banyasz, Marius P. Sumandea, C. William Balke, Leighton T. Izu, Xander H.T. Wehrens, Phosphorylation of RyR2 and shortening of RyR2 cluster spacing in spontaneously hypertensive rats with heart failure, Am. J. Phys, 293:H2409-17, 2007

Rashad J. Belin, Marius P. Sumandea, Edward A. Allen, Kelly Schoenfelt, Helen Wang, R. John Solaro, Pieter P. de Tombe, Augmented Protein Kinase C-alpha Induced Myofilament Protein Phosphorylation Contributes to Myofilament Dysfunction in Experimental Congestive Heart Failure, Circ Res, 101:195-204, 2007

Rashad J. Belin, Marius P. Sumandea, Tomoyoshi Kobayashi, Lori A. Walker, Veronica L. Rundell, Milana Yuzahakova, Stuart H. Ruch, David L. Geenen, R. John Solaro, Pieter P. de Tombe, Left Ventricular Myofilament Dysfunction in Rat Experimental Hypertrophy and Congestive Heart Failure, Am.J.Phys, 291:H2344-53, 2006

W. Glen Pyle, Gustavo La Rotta, Pieter P. de Tombe, Marius P. Sumandea, R. John Solaro, Control of Cardiac Myofilament Activation and PKC-?II Signaling Through the Actin Capping Protein, CapZ, J Mol Cell Cardiol, 41:537-43, 2006

Marius P. Sumandea, E.M. Burkart, T. Kobayashi, P. P. de Tombe, R. J. Solaro. Molecular and Integrated Biology of Thin Filament Protein Phosphorylation in Heart Muscle, Cardiac Engineering: From Genes and Cells to Structure and Function, ed. S. Sideman and R. Beyar, Volume 1015, Ann. NY Acad. Sci., 2004

E.M. Burkart, G.M. Arteaga, Marius P. Sumandea, R. Prabhakar, D.F. Wieczorek, R.J. Solaro, Altered Signaling Surrounding The C-Lobe of Cardiac Troponin C in Myofilaments Containing an Alpha-Tropomyosin Mutation Linked to Familial Hypertrophic Cardiomyopathy, J Mol Cell Cardiol, 35(10):1285-93, Oct 2003

Marius P. Sumandea, T. Kobayashi, W.G. Pyle, P. P. de Tombe, R. J. Solaro. Identification of Functionally Critical PKC Phosphorylation Residue of Cardiac Troponin T. J. Biol. Chem, 278(37):35135-44, 2003

E. M. Burkart, Marius P. Sumandea, M. Nili, T. Kobayashi, A. F. Martin, E. Homsher, R. J. Solaro, Charge Change at Protein Kinase C Sites of Phosphorylation on Cardiac Troponin I Affects Thin Filament Regulation. J. Biol. Chem, 278(13):11265, 2003

Other Publications