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Razvan L. Cornea

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Title

Razvan L. Cornea
Research Associate Professor

Department:

Research Description

Our goal is to understand the structure, function, and dynamics of protein complexes involved in the regulation of intracellular Ca2+ homeostasis, particularly (but not exclusively) in striated muscle. Our focus is primarily on the SERCA pump (and its regulator in the heart, phospholamban) and the ryanodine receptor (RyR, and its regulatory partners, FKBP, calmodulin, S100A1.). Both of these membrane protein complexes are prominent targets in the search for heart failure therapies using either biologicals or small-molecule strategies. 

To carry out our studies, we site-specifically label membrane protein complexes with fluorescent dyes, then monitor their interactions and structural changes using fluorescence spectroscopy, most often FRET, in isolated membranes or directly in-cell.

We use our understanding of the structure-function correlations within the SERCA and RyR complexes to help develop therapies for diseases of the skeletal and cardiac muscle.


Recent Publications

Hwang, H.S., Nitu, F.R., Yang, Y., Walweel, K., Pereira, L., Johnson, C.N., Faggioni, M., Chazin, W.J., Laver, D., George, A.L., Cornea, R.L., Bers, D.M., and Knollmann, B.C. (2014) Divergent Regulation of RyR2 Channels by Arrhythmogenic Human Calmodulin Mutants. Circ Res. Circ Res. 114, 1114-24..

Gruber, S.J., Cornea, R.L., Li, J., Peterson, K.C., Gillispie, G.D., Dahl, R., Zsebo, K.M., Robia, S.L., and Thomas, D.D. (2014) Intramolecular Time-Resolved FRET in Living Cells Detects Functional Modulators of the Ca-ATPase. J Biomol Screen. 19:215-22 (cover article).

Yang Y, Guo T, Oda T, Chakraborty A, Chen L,Knowlton AA, Fruen BR, Cornea RL, Meissner G, Bers DM. (2014) In Cardiac Myocytes, Z-Line Calmodulin Is Mainly RyR2-Bound and Heart Failure Decreases RyR2-CaM Affinity. Circ Res. 114:295-306.

Bleeker, N.P., Cornea, R.L., Thomas, D.D., Xing C. (2013) A Novel Inhibitor of the Sarco/Endoplasmic Reticulum Ca2+-ATPase Synergizes with Classic SERCA Inhibitors and Mitigates Multidrug-Resistant Leukemia. Mol. Pharmaceutics, 10:4358-4366.

Girgenrath, T., Mahalingam,M., Svensson,B., Nitu, F.R., Cornea, R.L., and Fessenden, J.D. (2013) N-terminal and Central Segments of the Type 1 Ryanodine Receptor (RyR1) Mediate Its Interaction with FK506 Binding Proteins. J. Biol. Chem. Epub 4/12/2013.

Oda, T., Yang, Y., Nitu, F.R., Svensson, B., Lu, X., Fruen, B.R., Cornea, R.L., and Bers D.M (2013) Binding of RyR2 “Unzipping” Peptide in Cardiomyocytes Activates RyR2 and Reciprocally Inhibits Calmodulin Binding. Circ. Res. 112, 487-97.

Cornea, R.L., Gruber, S.J., Lockamy, E.L., Muretta, J.M., Jin, D., Chen, J., Dahl, R., Bartfai, T., Zsebo, K.M., Gillispie, G.D., and Thomas, D.D. (2013) High-Throughput FRET Assay Yields Allosteric SERCA Activators. J  Biomol Screen. 18, 96-106.

Guo, T., Fruen, B.R., Nitu, F.R., Nguyen, T.D., Yang, Y., Cornea, R.L., & Bers, D.M. (2011) FRET Detection of Calmodulin Binding to the Cardiac RyR2 Calcium Release Channel. Biophys. J. 101, 2170-77.

Lockamy, E.L., Cornea, R.L., Karim, C.B., & Thomas, D.D. (2011) Functional and Physical Competition between Phospholamban and its Mutants Provides Insight into the Molecular Mechanism of Gene Therapy for Heart Failure. Biochem. Biophys. Res. Commun. 408,388-92.

Cornea, R.L., Nitu, F.R., Samsó, M., Thomas, D.D., & Fruen, B.R. (2010) Mapping The Ryanodine Receptor (RyR) FK506-Binding Protein (FKBP) Subunit Using Fluorescence Resonance Energy Transfer (FRET). J. Biol. Chem. 285, 19219-26, PMCID: 2885200.

Guo, T., Cornea, R.L., Huke, S., Camors, E., Yang, Y., Picht, E., Fruen, B.R., & Bers, D.M. (2010) Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized cardiac myocytes and effects on Ca sparks. Circ. Res. 106, 1743-1752, PMCID: 2895429.

Cornea, R.L., Nitu, F., Gruber, S., Kohler, K., Satzer, M., Thomas, D.D., and Fruen, B.R. (2009) FRET-based mapping of calmodulin bound to the RyR1 Ca2+ release channel. Proc Natl Acad Sci USA 106, 6128-6133, PMCID: 2662960.

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Cornea, R.L., Nitu, F.R., Samsó, M., Thomas, D.D., & Fruen, B.R. (2010) Mapping The Ryanodine Receptor (RyR) FK506-Binding Protein (FKBP) Subunit Using Fluorescence Resonance Energy Transfer (FRET). J. Biol. Chem. 285, 19219-26, PMCID: 2885200.

Guo, T., Cornea, R.L., Huke, S., Camors, E., Yang, Y., Picht, E., Fruen, B.R., & Bers, D.M. (2010) Kinetics of FKBP12.6 binding to ryanodine receptors in permeabilized cardiac myocytes and effects on Ca sparks. Circ. Res. 106, 1743-1752, PMCID: 2895429.

Cornea, R.L., Nitu, F., Gruber, S., Kohler, K., Satzer, M., Thomas, D.D., and Fruen, B.R. (2009) FRET-based mapping of calmodulin bound to the RyR1 Ca2+ release channel. Proc Natl Acad Sci USA 106, 6128-6133, PMCID: 2662960.

Fruen, B.R., Balog, E.M., Schafer, J., Nitu, F.R., Thomas, D.D., and Cornea, R.L. (2005) Direct detection of calmodulin tuning by ryanodine receptor channel targets using a Ca2+-sensitive acrylodan-labeled calmodulin. Biochemistry 44, 278-284.

Balog, E.M., Norton, L.E., Bloomquist, R.A, Cornea, R.L., Black, D.J., Louis, C.F., Thomas, D.D., and Fruen, B.R. (2003) Calmodulin oxidation and methionine to glutamine substitutions reveal methionine residues critical for functional interaction with RyR1. J. Biol. Chem. 278, 15615-15621.

Reddy, L.G., Cornea, R.L., Winters, D.L., McKenna, E., and Thomas, D.D. (2003) Defining the molecular components of calcium transport regulation in a reconstituted membrane system. Biochemistry 42, 4585-4592.

Jones, L.R., Cornea, R.L., and Chen, Z. (2002) Close proximity between residue 30 of phospholamban and cysteine 318 of the cardiac Ca2+-pump revealed by intermolecular thiol cross-linking. J. Biol. Chem. 277, 28319-28329.

Ph.D., University of Minnesota, 1997
Phone Number
612-626-2660
Email Address

corne002@umn.edu

Address
321 Church St SE
5-126 BSBE
Minneapolis, MN 55455