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Meredith  Bond
 

Meredith Bond Ph.D.

Academic Title: Adjunct Professor
Primary Appointment: Physiology
m.bond40@csuohio.edu

Personal History:

I grew up in Sydney, Australia. Obtained a B.A. from Macquarie University in Sydney in 1976. Worked for two years as a technician for Britton Chance at the University of Pennsylvania and then obtained a PhD in Physiology from the Pennsylvania Muscle Institute and Dept of Physiology, University of Pennsylvania. I was then a post-doctoral fellow and Research Associate with Andrew and Avril Somlyo at the University of Pennsylvania. I moved to Cleveland in 1986 to take up a position as Staff in the Department of Molecular Cardiology in the Research Institute of the Cleveland Clinic Foundation. I also had an adjunct faculty appointment in the Department of Physiology and Biophysics, Case Western Reserve University. My research has been continually funded by NIH. Over the years, I was fortunate to have four graduate students obtain their PhD in my lab, over 15 post-doctoral fellows train with me and over 25 undergraduate students spend summers in my lab. I moved to Baltimore in September 2003 to become Professor and Chair of the Department of Physiology at the University of Maryland School of Medicine. In 2011, I left Baltimore to become the Dean of the College of Sciences and Health Professions at Cleveland State University in Cleveland, OH.

 

Research Interests:

Area of general research interest:

β-adrenergic pathways in hypertrophied and failing hearts, cardiac function, role of protein kinases, regulation of phosphorylation of myofibrillar proteins in the heart; role of A-kinase anchoring proteins (AKAPs) in protein kinase A (PKA) targeting; genomic and proteomic analysis of human heart failure.

Current program:

β-adrenergic pathways and troponin I phosphorylation in hypertrophied and failing hearts; gene expression profiling in human heart failure.

Regulation of cAMP dependent protein kinase (PKA) is determined in part by sub-cellular targeting of PKA by A-kinase anchoring proteins (AKAPs). Anchoring of PKA by AKAPs increases the local concentration of PKA, thus directing the kinase to specific substrates. My lab investigates downstream regulation of the β-adrenergic signaling pathway by AKAP targeted PKA. Our work in animal models of cardiac hypertrophy and failure and in failing human hearts has shown that this downstream regulation of the β-adrenergic signal transduction pathway is impaired in diseased hearts, resulting in altered substrate phosphorylation.

We are currently investigating the functional role of AKAPs in the heart. We have disrupted PKA interaction with endogenous AKAPs in cardiac myocytes by introducing an inhibitory peptide, Ht31, via adenoviral gene transfer. Our results provide the first evidence of the importance of PKA targeting by AKAPs in the regulation of PKA substrate phosphorylation and of cardiac contractility., We are currently introducing Ht31 peptide by adenoviral gene transfer into rat hearts in vivo and determining the effect on cardiac contractility by echocardiography. We have also identified a novel AKAP in the heart - the intermediate filament protein, synemin. We hypothesize that synemin targets PKA to the cytoskeleton, regulating phosphorylation of cytoskeletal and sarcomeric substrates.

We are also performing gene expression profiling in failing and non-failing human hearts by high density oligonucleotide arrays. These measurements allow identification of clusters of genes with altered expression in human heart failure and have revealed distinct gene fingerprints of human heart failure of different etiologies.

Lab Techniques and Equipment:

  • Isolation of rat cardiac myocytes and measurement of cytosolic Ca2+ and cell shortening
  • Adenoviral gene transfer in isolated myocytes and rat heart in vivo
  • Non-invasive assessment of cardiac contractility in rodents by echocardiography
  • Fluorescent resonance energy transfer of GFP-tagged proteins and peptides in cells
  • Oligonucleotide microarray analysis of gene expression in the heart
  • Measurement of substrate phosphorylation by back-phosphorylation and by mass-spectrometry
  • Expression of wild type and mutant AKAPs and PKA in CHO and HEK cells
  • Confocal microscopy and immunofluorescent microscopy
  • Immunoprecipitation

Publications:


1.       Tan, F.L., Moravec, C.S., Li, J., Apperson-Hansen, C., McCarthy, P.M., Young, J.B. and Bond, M. (2002) Gene expression fingerprint as a predictor of human heart failure and its etiology. Proc Natl Acad Sci USA 99: 11387-11392.

2.       Ruse, C.I., Willard, B., Jin, J.P., Haas, T., Kinter, M. and Bond, M. (2002) Kinetics and stoichiometry of protein phosphorylation at the amino acid level. Anal Chem, 74: 1658-1664.

3.       Ruehr, M.R., Russell, M.A., Ferguson, D., Scott, J.D., Bhat, M., Ma, J., Damron, D.S. and Bond, M. (2003) Targeting of protein kinase A by muscle A kinase-anchoring protein (mAKAP) regulates phosphorylation and function of the skeletal muscle ryanodine receptor. J Biol Chem, 278: 24831-24836.

4.       Masri, S.C., Yamani, M.H., Russell, M.A., Ratliff, N.B., Yang, J., Almasan, A., Apperson-Hansen, C., Li, J., Starling, R.C., McCarthy, P., Young, J.B. and Bond, M. (2003) Sustained apoptosis in human cardiac allografts despite histologic resolution of rejection. Transplantation, 76: 859–864.

5.       Ruse, C.I., Kinter, M. and Bond, M. (2004) Integrated analysis of the human cardiac transcriptome, proteome and phosphoproteome. Proteomics, 4: 1505-1516.

6.       Ruehr, M.L., Russell, M.R. and Bond, M. (2004) A-Kinase Anchoring Protein targeting of Protein Kinase A in the heart. J Mol Cell Cardiol, 37(3): 653-665.

7.       Barbato, J.C., Huang, Q-Q., Hossain, M.M., Bond, M. and Jin, J-P. (2005) Proteolytic N-Terminal Truncation of Cardiac Troponin I Enhances Ventricular Diastolic Function. J. Biol. Chem., 280: 6602 – 6609.

8.       Riddle, E., Schwartzman, R., Bond, M. and Insel, P. (2005) Multi-tasking RGS Proteins in the Heart: The next Therapeutic Target? Circ Res., 96: 401-411.

9.       Russell, M., Lund, L.M., Haber, R., McKeegan, K., Cianciola, N., Mizuno, Y., Bond, M. (2006) The Intermediate Filament Protein Synemin is an A-kinase Anchoring Protein. Arch Biochem Biophys, 456(2): 204-15.

10.   Barrows, B.R., Azimzadeh, A.A., Zhou, H., Vives-Rodriguez, G., McCulle, S.L., Stark, W.N., Ambulos, N., Jing, Y., Pierson, R.N. III, Johnson, F.L., Balke, C.W., Gottlieb, S.S., and Bond, M. (2007) Robust gene expression analysis using amplified RNA from biopsy-sized human heart tissue. J Mol Cell Cardiol, 42(1): 260-4.

11.   Mauban, JH, O’Donnell, M, Warrier, S, Manni, S, and Bond, M. AKAP-scaffolding proteins and regulation of cardiac physiology. Physiology (Bethesda). 2009 Apr;24:78-87.  PMCID: PMC2751630

12.   Manni S, Mauban JH, Ward CW, Bond M. Phosphorylation of the PKA regulatory subunit modulates PKA-AKAP interaction, substrate phosphorylation and calcium signaling in cardiac cells. J Biol Chem 283(35): 24145-24154, 2008.  PMCID: PMC2527120