Loading...

Molecular Cardiovascular Biology

Division Photo

MCB Photo

First Row: M. Krenz, J. Robbins; Second Row: J. Molkentin, K. Yutzey, J. James, Z. Khuchua; Third Row: H. Nakayama, J. Gulick, S. Sadayappan, S. Ware, C. Baines

Division Data Summary
Research and Training Details
Number of Faculty12
Number of Joint Appointment Faculty1
Number of Research Fellows25
Number of Research Students11
Number of Support Personnel2
Direct Annual Grant Support $5,468,739
Direct Annual Industry Support $85,085
Peer Reviewed Publications37

Faculty Members

Jeffrey Robbins, PhD,  Professor
Christopher Baines, PhD,  Research Instructor
Melissa Colbert, PhD,  Research Associate Professor
James Gulick, MS,  Research Instructor
Jeanne James, MD,  Research Associate Professor
Zaza Khuchua, PhD,  Research Associate Professor
Maike Krenz, MD,  Research Instructor
Jeffery Molkentin, PhD,  Professor
Hiroyuki Nakayama, MD, PhD,  Research Instructor
Sakthivel Sadayappan, PhD,  Research Instructor
Stephanie Ware, MD, PhD,  Assistant Professor
Katherine Yutzey, PhD,  Professor

Joint Appointment Faculty Members

D. Woodrow Benson, MD, PhD,  Professor
Cardiology

Trainees

  • Mannix Auger-Messier, PhD,  N/A,  University of Sherbrooke, Canada
  • Bedard James, PhD,  N/A,  University of Cincinnati
  • Santanu Chakraborty, PhD,  N/A,  Miami University
  • Petra Eder, PhD,  N/A,  University of Graz, Austria
  • John Elrod, PhD,  N/A,  Albert Einstein College of Medicine
  • Heather Evans-Anderson, PhD,  N/A,  University of South Carolina School of Medicine
  • Ambrose Goonasekera, PhD,  N/A,  University of Rochester
  • Michael Hambleton, PhD,  N/A,  University of Cincinnati
  • Joerg Heineke, MD,  N/A,  Hannover Medical School, Germany
  • Izhak Kehat, PhD,  N/A,  Technion-Israel Institute of Technology, Isreal
  • Jennifer Kwong, PhD,  N/A,  Weill Medical College of Cornell University
  • Qinghang Liu, MD, PhD,  N/A,  University of Tennessee Health Sciences Center
  • Jeffrey Lynch, PhD,  N/A,  University of Alberta, Canada
  • Marjorie Maillet, PhD,  N/A,  University of Paris XI, France
  • Alina Maloyan, PhD,  N/A,  Hebrew University of Jerusalem, Israel
  • Douglas Millay, PhD,  N/A,  University of Cincinnati
  • Tomoki Nakamura, MD,  N/A,  Jichi Medical School, Japan
  • Hiroyuki Nakayama, MD, PhD,  N/A,  Osaka University School of Medicine, Japan
  • J. Scott Pattison, PhD,  N/A,  University of Missouri-Columbia
  • Malgorazata Quinn, PhD,  N/A,  Polish Academy of Sciences, Poland
  • Arunima Sengupta, PhD,  N/A,  Miami University
  • Anup Tilak, PhD,  N/A,  Industrial Toxicology Research Centre, India
  • Jop van Berlo, MD, PhD,  N/A,  University Hospital Maastricht, Netherlands
  • Shuyun Wang, MD, PhD,  N/A,  Shandong University, China
  • Xu Wu, MD, PhD,  N/A,  Loyola University Medical Center

Significant Accomplishments in FY08

$9 Million NIH L&B Grant

The Division received a major program grant totaling over 9 million dollars from the National Institute of Heart, Lung and Blood. The work will be carried out in the laboratories of three divisional faculty and will center around understanding important signaling pathways that underlie heart development and function.

Significant Publications in FY08

Pattison JS, Sanbe A, Maloyan A, Martin L, Osinska H, Klevitsky R, Robbins J (2008) Cardiomyocyte Expression of a Polyglutamine Pre-amyloid Oligomer Causes Heart Failure. Circulation 117: 2743-2751

This manuscript establishes the toxicity of a certain kind of unfolded protein that is found very often in diseased pediatric and adult heart patients. Proving that this protein causes heart disease now allows us to focus on developing ways of interfering with that process.

Millay DP, Sargent MA, Osinska H, Barton ER, Vaugniaux G, Sweeney HL, Robbins J, Molkentin JD (2008) Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy.  Nat. Med.  14:442-447.

This manuscript shows a novel way to treat muscular dystrophy in mice by blocking mitochondrial-dependent necrosis.  It suggests a novel treatment strategy for translation in to Duchenne MD boys.

Evans-Anderson HJ, Alfieri CM, Yutzey KE (2008)  Regulation of cardiomyocyte proliferation and myocardial growth during development by FoxO transcription factors.  Circ. Res. 102:686-694.
Baines CP, Kaiser RA, Sheiko T, Craigen WJ, Molkentin JD (2007) Voltage-dependent anion channels are dispensible for mitochondrial-dependent cell death. Nat. Cell Biol. 9:550-555.
Heineke J, Auger-Messier M, Xu J, Oka T, Sargent MA, York A, Klevitsky R, Vaikunth S, Duncan SA, Aronow BJ, Robbins J, Crombleholme TM, Molkentin JD (2007) Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the heart. J. Clin. Invest. 117:3198-3210.

Division Collaboration

Collaboration with Molecular Cardiovascular Biology; Cardiology; Cardiology

Collaborating Faculty: Katherine Yutzey; D. Woodrow Benson; Robert Hinton

Hinton RB, Alfieri C, Witt S, Glascock B, Khoury PR, Benson DW, Yutzey KE. (2008) Mouse Heart ValveStructure and Function: Echocardiographic and Morphometric Analyses from the Fetus through the Aged Adult.  Am. J. Physiol. – Heart and Circ. Physiol. 294:H2480-2488.

Return to Top
Loading...

Division Publications

  1. Baines CP. The mitochondrial permeability transition pore as a target of cardioprotective signaling. Am J Physiol Heart Circ Physiol. 2007; 293: H903-4.
  2. Millay DP, Sargent MA, Osinska H, Baines CP, Barton ER, Vuagniaux G, Sweeney HL, Robbins J, Molkentin JD. Genetic and pharmacologic inhibition of mitochondrial-dependent necrosis attenuates muscular dystrophy. Nat Med. 2008; 14: 442-7.
  3. Nakayama H, Chen X, Baines CP, Klevitsky R, Zhang X, Zhang H, Jaleel N, Chua BH, Hewett TE, Robbins J, Houser SR, Molkentin JD. Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. J Clin Invest. 2007; 117: 2431-44.
  4. Pattison JS, Waggoner JR, James J, Martin L, Gulick J, Osinska H, Klevitsky R, Kranias EG, Robbins J. Phospholamban overexpression in transgenic rabbits. Transgenic Res. 2008; 17: 157-70.
  5. Nakamura T, Colbert M, Krenz M, Molkentin JD, Hahn HS, Dorn GW, 2nd, Robbins J. Mediating ERK 1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndrome. J Clin Invest. 2007; 117: 2123-32.
  6. Diwan A, Krenz M, Syed FM, Wansapura J, Ren X, Koesters AG, Li H, Kirshenbaum LA, Hahn HS, Robbins J, Jones WK, Dorn GW. Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice. J Clin Invest. 2007; 117: 2825-33.
  7. Krenz M, Sadayappan S, Osinska HE, Henry JA, Beck S, Warshaw DM, Robbins J. Distribution and structure-function relationship of myosin heavy chain isoforms in the adult mouse heart. J Biol Chem. 2007; 282: 24057-64.
  8. Ago T, Liu T, Zhai P, Chen W, Li H, Molkentin JD, Vatner SF, Sadoshima J. A redox-dependent pathway for regulating class II HDACs and cardiac hypertrophy. Cell. 2008; 133: 978-93.
  9. Davies KJ, Ermak G, Rothermel BA, Pritchard M, Heitman J, Ahnn J, Henrique-Silva F, Crawford D, Canaider S, Strippoli P, Carinci P, Min KT, Fox DS, Cunningham KW, Bassel-Duby R, Olson EN, Zhang Z, Williams RS, Gerber HP, Perez-Riba M, Seo H, Cao X, Klee CB, Redondo JM, Maltais LJ, Bruford EA, Povey S, Molkentin JD, McKeon FD, Duh EJ, Crabtree GR, Cyert MS, de la Luna S, Estivill X. Renaming the DSCR1/Adapt78 gene family as RCAN: regulators of calcineurin. Faseb J. 2007; 21: 3023-8.
  10. Gurda GT, Guo L, Lee SH, Molkentin JD, Williams JA. Cholecystokinin Activates Pancreatic Calcineurin-NFAT Signaling In Vitro and In Vivo. Mol Biol Cell. 2008; 19: 198-206.
  11. Houser SR, Molkentin JD. Does contractile Ca2+ control calcineurin-NFAT signaling and pathological hypertrophy in cardiac myocytes?. Sci Signal. 2008; 1: pe31.
  12. Jobe SM, Wilson KM, Leo L, Raimondi A, Molkentin JD, Lentz SR, Di Paola J. Critical role for the mitochondrial permeability transition pore and cyclophilin D in platelet activation and thrombosis. Blood. 2008; 111: 1257-65.
  13. Manicassamy S, Gupta S, Huang Z, Molkentin JD, Shang W, Sun Z. Requirement of calcineurin a beta for the survival of naive T cells. J Immunol. 2008; 180: 106-12.
  14. Morancho B, Minguillon J, Molkentin JD, Lopez-Rodriguez C, Aramburu J. Analysis of the transcriptional activity of endogenous NFAT5 in primary cells using transgenic NFAT-luciferase reporter mice. BMC Mol Biol. 2008; 9: 13.
  15. Sahin B, Hawasli AH, Greene RW, Molkentin JD, Bibb JA. Negative regulation of cyclin-dependent kinase 5 targets by protein kinase C. Eur J Pharmacol. 2008; 581: 270-5.
  16. Snider P, Hinton RB, Moreno-Rodriguez RA, Wang J, Rogers R, Lindsley A, Li F, Ingram DA, Menick D, Field L, Firulli AB, Molkentin JD, Markwald R, Conway SJ. Periostin is required for maturation and extracellular matrix stabilization of noncardiomyocyte lineages of the heart. Circ Res. 2008; 102: 752-60.
  17. Hsieh PC, Segers VF, Davis ME, MacGillivray C, Gannon J, Molkentin JD, Robbins J, Lee RT. Evidence from a genetic fate-mapping study that stem cells refresh adult mammalian cardiomyocytes after injury. Nat Med. 2007; 13: 970-4.
  18. Pattison JS, Sanbe A, Maloyan A, Osinska H, Klevitsky R, Robbins J. Cardiomyocyte expression of a polyglutamine preamyloid oligomer causes heart failure. Circulation. 2008; 117: 2743-51.
  19. Pinz I, Robbins J, Rajasekaran NS, Benjamin IJ, Ingwall JS. Unmasking different mechanical and energetic roles for the small heat shock proteins CryAB and HSPB2 using genetically modified mouse hearts. Faseb J. 2008; 22: 84-92.
  20. Wolf CM, Arad M, Ahmad F, Sanbe A, Bernstein SA, Toka O, Konno T, Morley G, Robbins J, Seidman JG, Seidman CE, Berul CI. Reversibility of PRKAG2 glycogen-storage cardiomyopathy and electrophysiological manifestations. Circulation. 2008; 117: 144-54.
  21. Hambleton M, York A, Sargent MA, Kaiser RA, Lorenz JN, Robbins J, Molkentin JD. Inducible and myocyte-specific inhibition of PKCalpha enhances cardiac contractility and protects against infarction-induced heart failure. Am J Physiol Heart Circ Physiol. 2007; 293: H3768-71.
  22. Heineke J, Auger-Messier M, Xu J, Oka T, Sargent MA, York A, Klevitsky R, Vaikunth S, Duncan SA, Aronow BJ, Robbins J, Crombleholme TM, Molkentin JD. Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the murine heart. J Clin Invest. 2007; 117: 3198-210.
  23. Oka T, Xu J, Kaiser RA, Melendez J, Hambleton M, Sargent MA, Lorts A, Brunskill EW, Dorn GW, 2nd, Conway SJ, Aronow BJ, Robbins J, Molkentin JD. Genetic manipulation of periostin expression reveals a role in cardiac hypertrophy and ventricular remodeling. Circ Res. 2007; 101: 313-21.
  24. Pinz I, Ostroy SE, Hoyer K, Osinska H, Robbins J, Molkentin JD, Ingwall JS. Calcineurin-induced energy wasting in a transgenic mouse model of heart failure. Am J Physiol Heart Circ Physiol. 2008; 294: H1459-66.
  25. Purcell NH, Wilkins BJ, York A, Saba-El-Leil MK, Meloche S, Robbins J, Molkentin JD. Genetic inhibition of cardiac ERK1/2 promotes stress-induced apoptosis and heart failure but has no effect on hypertrophy in vivo. Proc Natl Acad Sci U S A. 2007; 104: 14074-9.
  26. Nagayama T, Takimoto E, Sadayappan S, Mudd JO, Seidman JG, Robbins J, Kass DA. Control of in vivo left ventricular [correction] contraction/relaxation kinetics by myosin binding protein C: protein kinase A phosphorylation dependent and independent regulation. Circulation. 2007; 116: 2399-408.
  27. Sadayappan S, Finley N, Howarth JW, Osinska H, Klevitsky R, Lorenz JN, Rosevear PR, Robbins J. Role of the acidic N' region of cardiac troponin I in regulating myocardial function. Faseb J. 2008; 22: 1246-57.
  28. Sadayappan S, Robbins J. The death of transcriptional chauvinism in the control and regulation of cardiac contractility. Ann N Y Acad Sci. 2008; 1123: 1-9.
  29. Yasuda S, Coutu P, Sadayappan S, Robbins J, Metzger JM. Cardiac transgenic and gene transfer strategies converge to support an important role for troponin I in regulating relaxation in cardiac myocytes. Circ Res. 2007; 101: 377-86.
  30. Ware SM, Quinn ME, Ballard ET, Miller E, Uzark K, Spicer RL. Pediatric restrictive cardiomyopathy associated with a mutation in beta-myosin heavy chain. Clin Genet. 2008; 73: 165-70.
  31. Villar AJ, Ware SM. "Developmental Origins of the Mammalian Body Plan." New York: Oxford University Press; 2008: 57-68.
  32. Ware SM, Belmont JW. "ZIC3, CFC1, ACVR2B and EBAF and the Visceral Heterotaxies." New York: Oxford University Press; 2008: 373-381.
  33. Evans-Anderson HJ, Alfieri CM, Yutzey KE. Regulation of cardiomyocyte proliferation and myocardial growth during development by FOXO transcription factors. Circ Res. 2008; 102: 686-94.
  34. Hinton RB, Jr., Alfieri CM, Witt SA, Glascock BJ, Khoury PR, Benson DW, Yutzey KE. Mouse heart valve structure and function: echocardiographic and morphometric analyses from the fetus through the aged adult. Am J Physiol Heart Circ Physiol. 2008; 294: H2480-8.
  35. Shelton EL, Yutzey KE. Twist1 function in endocardial cushion cell proliferation, migration, and differentiation during heart valve development. Dev Biol. 2008; 317: 282-95.
  36. Shelton EL, Yutzey KE. "Heart development and T-box transcription factors: lessons from avian embryos." Amsterdam ; Boston: Elsevier; 2008: 69-91.
  37. Yutzey KE. Teed off: cardiac conduction system development requires T-box transcription factors. Circ Res. 2008; 102: 1295-7.
Return to Top
Loading...

Grants, Contracts, and Industry Agreements

Grant and Contract Awards Annual Direct / Project Period Direct

Baines, C

Mechanisms of Mitochondrial-Dependent Myocyte Death
0635134N07/01/06 - 06/30/10 $59,091 / $236,634

Bedard, J

Genetic and Molecular Roles of a Novel ZIC3 Isoform in Cardiovascular Development
0725539B07/01/07 - 06/30/09 $42,000 / $86,000

Combs, M

NFATc1 Regulation of Extracelluar Matrix Remodeling and Cell Proliferation in Heart Valve Development
0715107B07/01/07 - 06/30/09 $21,000 / $42,000

Khuchua, Z

Animal Models of Human Barth Syndrome, A Mitochondrial Cardiolipin Disorder
07/01/07 - 06/30/09 $49,500 / $55,000

Krenz, M

Defective Valvulogenesis in Noonan Syndrome
0635472N07/01/06 - 06/30/10 $59,091 / $236,364

Liu, Q

The Role of Apoptosis Signal-Regulating Kinase-1 in Regulation of Cardiac Growth and Cell Death in Adult Heart in Vivo
0625543B07/01/06 - 06/30/08 $44,000 / $86,000

Maillet, M

Calcineurin's Role in Regulating Heart Growth & Hypertrophy
0625282B07/01/06 - 06/30/08 $44,000 / $86,000

Molkentin, J

Molecular Pathways Controlling Cardiac Gene Expression
R01 HL 06056207/01/03 - 06/30/08 $213,341 / $1,125,000
Cardiac Hypertrophic Intracellular Signaling Pathways
R01 HL 06292708/01/03 - 07/31/08 $189,636 / $1,000,000
Genetic and Molecular Signaling in Heart Failure: Core D
P50 HL 07710101/01/08 - 12/31/09 $278,020 / $564,381
Mitochondrial Regulated Cardiac Myocyte Death
R01 HL 08110408/01/05 - 07/31/09 $237,045 / $1,000,000
Genetic and Molecular Signaling in Heart Failure
P50 HL 07710102/22/05 - 12/31/09 $275,962 / $1,451,722
Role of Calcium Influx in Miyoshi Myopathy and Other Forms of Muscular Dystrophy
05/01/07 - 04/30/10 $70,000 / $210,000
Adaptive and Maladaptive Signaling in Cardiac Growth and Regeneration
10/01/05 - 09/30/10 $293,618 / $1,184,852
Calcium as a Molecular Signal in the Heart
R01 HL 08931208/15/07 - 06/30/12 $249,169 / $1,245,845

Pattison, S

The Role of Mitochondrial Dysfunction and Apoptosis in CryABR120G Heart Failure
F32 HL 08747811/18/07 - 11/17/09 $50,546 / $66,401

Robbins, J

Investigation of Amyloid Oligomer in Pediatric Cardiovascular Disease
06/03/07 - 03/31/10 $38,409 / $122,557
Molecular Basis of Dilated and Hypertrophic Cardiomyopathy
P01 HL 05940812/01/04 - 11/30/09 $59,059 / $320,627
Genetic and Molecular Signaling in Heart Failure
P50 HL 07710102/22/05 - 12/31/09 $349,154 / $1,837,616
Cardiomyocyte Toxicity and Heart Failure in Desmin Related Cardiomyopathy
R01 HL 08786202/01/08 - 01/31/11 $150,000 / $400,000
Signaling Processes Underlying Cardiovascular Function
P01 HL 06977901/11/08 - 12/31/12 $1,236,664 / $6,163,688
SCCOR in Pediatric Heart Development and Disease
P50 HL 07472802/15/04 - 01/31/09 $342,085 / $1,041,874

Sadayappan, S

Phosphorylation and Function of Cardiac Myosin Binding Protein-C
0830311N01/01/08 - 12/31/11 $70,000 / $280,000

Shelton, E

The Functions of Tbx20 and Twist 1 in Endocardial Cushion Development
0715360B07/01/07 - 06/30/08 $21,000 / $21,000

Strauss, A

Adaptation to Long Chain Fatty Acid Oxidation Deficiency
R01 HL 07541208/01/07 - 02/28/09 $192,050 / $192,050
A Multi-Center Group to Study Acute Liver Failure in Children
U01 DK 07214609/01/07 - 08/31/08 $26,017 / $26,017

Wang, S

Determination of Cardiac Looping: Role of Zic 3 at the Node
0725562B07/01/07 - 06/30/09 $42,000 / $86,000

Ware, S

Development of Novel Resequencing Chip to Diagnose Pediatric Cardiomyopathy
04/01/08 - 03/31/09 $49,750 / $49,750
Requirement of the Embryonic Node for Cardiac Looping
R01 HL 08863904/01/07 - 03/31/12 $250,000 / $1,250,000

Yutzey, K

Tbx20 Regulation of Heart Valve Development
R01 HL 08271607/01/06 - 05/31/10 $242,750 / $1,000,000
SCCOR in Pediatric Development and Disease
P50 HL 07472802/15/04 - 01/31/09 $223,782 / $681,564
Current Year Direct$5,468,739
Industry Contracts

Molkentin, J

$ 46,046
$ 39,039
Current Year Direct Receipts$85,085
Total$5,553,824
Return to Top
Loading...