Mark T. Ziolo, Ph.D.

Assistant Professor

019 Hamilton Hall (office)
034 Hamilton Hall (lab)
1645 Neil Avenue
Columbus OH 43210-1218

614-688-7905 (office)
614-688-7900 (lab)
614-688-7999 (fax)
ziolo.1@osu.edu

Education:
Ph.D., Physiology and Biophysics, University of Illinois, Chicago, IL

Research Interests:
My research area is excitation-contraction coupling in the heart using state-of-the-art electrophysiological and optical methods. The focus of my research is how nitric oxide and/or cyclic GMP alter cardiac myocite function. Other areas include b-adrenergic signaling and human heart failure.

Techniques Available:
We use a variety of state-of-the-art techniques in the lab to study cardiac myocyte function- epifluorescence (to measure Ca²⁺ and NO), video edge detection (cell shortening), patch clamp (whole cell voltage clamp for I_Ca, I_Kr, I_Ks, I_K1, NCX and current clamp for action potentials), and confocal microscopy (line scan mode- Ca²⁺ sparks). I have 2 experimental setups in which we use patch clamp, epifluorescence and/or video edge detection and there is a confocal microscope in DHLRI.

Laboratory Environment:
The general area of research for my lab is investigating Excitation-Contraction Coupling (EC Coupling) in the heart. More specifically, I examine the effects of nitric oxide (NO) on ECC. NO is a free radical that is produced in cardiac myocytes via enzymes termed NO synthase (NOS). There are 3 isoforms of NOS, and all 3 are expressed in myocytes. The lab studies the effect of all 3 isoforms on cardiac function. Other areas of interest include the effects of b-adrenergic stimulation and disease states (e.g., heart failure) on cardiac myocyte EC coupling.

Studies performed in the lab are done on isolated cardiac myocytes (the muscle cells of the heart). We isolate the myocytes from a variety of animals- transgenic mice (NOS1^-/-, NOS3^-/-, NOS2^-/-, a cardiac specific, inducible overexpression of NOS2, and others (through collaborations), rabbits (control and adenovirus-mediated overexpression (in culture), failing human hearts (from transplant recipients or LVAD implants) and a canine heart failure model.

Laboratory Members:
Honglan Wang, Ph.D., Postdoctoral Researcher
Christopher Traynham, Graduate Student
Saamia Hossain, Student Assistant
Dr. Ziolo
Lifei Tang, Graduate Student
SteveRoof, Graduate Student

Collaborators:
Paul M.L. Janssen, Ph.D., The Ohio State University
Muthu Periasamy, Ph.D., The Ohio State University
Sandor Gyorke, Ph.D., The Ohio State University
David Feldman, M.D., Ph.D., The Ohio State University
Cynthia Carnes, Ph.D., The Ohio State University
Jeff Molkentin, Ph.D., Cincinnati Children's Hospital Medical Center
Tom Shannon, D.V.M., Ph.D., Rush University
Litsa Kranias, Ph.D., University of Cincinnati
Jay Zweier, M.D., The Ohio State University
Jonathan P. Davis, Ph.D., The Ohio State University

Selected Publications:

Kohr MJ, Wang H, Wheeler DG, Velayutham M, Zweier JL, Ziolo MT. Targeting of phospholamban by peroxynitrite decreases ?-adrenergic stimulation in cardiomyocytes. Cardiovasc Res. 77(2):353–361, 2008.
Feldman DS, Elton TS, Sun B, Martin MM, Ziolo MT. Mechanisms of Disease: Detrimental Adrenergic Signaling in Acute Decompensated Heart Failure. Nat Clin Pract Cardiovasc Med. 5:208-218, 2008.
Wang H, Kohr MJ, Wheeler DG, Ziolo MT. Endothelial Nitric Oxide Synthase Decreases ?-adrenergic Responsiveness via Inhibition of the L-type Ca²⁺ Current. Am J Physiol-Heart. 294 H1473-H1480, 2008.
Ziolo MT. The Fork in the Nitric Oxide Road: Cyclic GMP or Nitrosylation. Nitric Oxide. 18(3):153-156, 2008.
Kohr MJ, Wang H, Wheeler DG, Velayutham M, Zweier JL, Ziolo MT. Biphasic effect of SIN-1 is reliant upon cardiomyocyte contractile state. Free Radical Biology and Medicine. 45:73-80, 2008.
Wang H, Kohr MJ, Traynham CJ, Wheeler DG, Janssen PM, Ziolo MT. Neuronal nitric oxide synthase signaling within cardiac myocytes targets phospholamban. Am J Physiol-Cell Physiology. 294:C1566-C1575, 2008.
DeSantiago J, Ai X, Islam M, Acuna G, Ziolo MT, Bers DM, Pogwizd SM. Arrhythmogenic effects of ?₂-adrenergic stimulation in the failing heart are attributable to enhanced Sarcoplasmic Reticulum Ca Load. Circ Res. 102:1389-1397, 2008.
Ziolo MT, Kohr MJ, Wang H. Nitric oxide Signaling and Myocardial Function. Invited Review. J Mol Cell Cardiol. 45(5):625-32, 2008.
Kohr MJ, Davis JP, Ziolo MT. Peroxynitrite increases protein phosphatase activity and promotes the interaction of phospholamban with protein phosphatase 2a in the myocardium. Nitric Oxide. 20(3): 217-221, 2009.
Wang H, Kohr MJ, Traynham CJ, Ziolo MT. Phosphodiesterase 5 Restricts NOS3/Soluble Guanylate Cyclase Signaling to L-type Ca²⁺ current in Cardiac Myocytes. J Mol Cell Cardiol. 47(2):304-14, 2009.
Kohr MJ, Tocchetti CG, Gao WD, Kass DA, Paolocci N, Ziolo MT. Nitroxyl Enhances Cardiomyocyte Contraction by Increasing Sarcoplasmic Reticulum Ca²⁺-Cycling Independent of L-Type Ca²⁺ Current. Frontiers in Bioscience. 2:614-26, 2010.
Doshi AA, Ziolo MT, Wang H, LesinskiA, Binkley PF. A promoter polymorphism of the endothelial nitric oxide synthase gene is associated with reduced mRNA and protein expression in failing human myocardium. J Cardiac Failure. In Press.
Kohr MJ, Traynham CJ, Davis JP, Ziolo MT. cAMP-independent activation of protein kinase A by the Peroxynitrite Generator SIN-1 elicits positive inotropic effects in cardiomyocytes. J Mol Cell Cardiol. In Press.

Ongoing Projects:
Regulation of cardiac myocyte contractile function by reactive nitrogen species (nitric oxide, peroxynitrite, etc.). Other areas include ?-adrenergic signaling and human heart failure.

External Grants:
• NIH R01 HL079283 07/01/2006-06/30/2011, P.I. - Mark T. Ziolo
• NIH K02 HL094692 01/01/2009-12/31/2014, P.I.- Mark T Ziolo

• NIH ARRA Challenge Grant RC1 HL099538-0110, 10/01/2009-09/30/2011, P.I.- Paul Janssen, CoPI- Ziolo

• NIH R01 HL084498 07/01/2007-06/30/2012, P.I. - David Feldman, CoPI - Ziolo

• NIH F31 HL096435 7/1/09-6/30/11, Christopher Traynham, Graduate Student, Mentor – Ziolo

Lab Graduates:

Dr. Mark Kohr (IBGP, defended March, 2009). Current position: Postdoctoral Fellow with a joint appointment at Johns Hopkins University and National Institutes of Health (mentors: Drs. Charles Steenbergen and Elizabeth Murphy).