Burns C. Blaxall, PhD, FAHA
Director of Translational Science, Heart Institute
is interested in understanding the molecular mechanisms associated with the development and progression of heart failure. We are particularly interested in developing novel heart failure therapeutics targeting myocardial function and fibrosis. To this end, we also seek to understand the pathologic role of cardiac myocyte and non-myocyte (i.e.. fibroblast) intercellular communication.
513-803-4005
burns.blaxall@cchmc.org
Burns C. Blaxall, PhD, FAHA
Director of Translational Science, Heart Institute
Academic Information
Professor, UC Department of Pediatrics
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Specialties
Molecular and signaling mechanisms of heart failure; cardiac fibrosis; drug and therapeutic discovery
Biography
Dr. Burns C. Blaxall has focused his entire career on understanding the molecular mechanisms of heart failure. He received his PhD in Pharmacology from the University of Colorado Health Sciences Center, and postdoctoral training at Duke University Medical Center. He then rose through the faculty ranks at the University of Rochester Medical Center and the Aab Cardiovascular Research Institute, where he also directed the Howard Hughes Medical Institute Med-into-Grad Fellowship in Cardiovascular Science. In 2012, he was recruited to the Heart Institute of Cincinnati Children’s Hospital Medical Center, where he is director of Translational Science. Dr. Blaxall has received many academic honors, including the Early Career Investigator Award from the American Heart Association (AHA), the Outstanding Achievement Award from the Founder’s AHA Affiliate, the Merit Award for Research Achievement from Mended Hearts, and election as Fellow of the AHA.
Education and Training
PhD: University of Colorado HSC, Denver, CO, 1999. Fellowship: Duke University Medical Center, Durham, NC.
Publications
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Martin ML, Blaxall BC. Cardiac intercellular communication: are myocytes and fibroblasts fair-weather friends? J Cardiovasc Transl Res. 2012. Jaffré F, Friedman AE, Hu Z-Y, Mackman N and Blaxall BC. Beta-adrenergic receptor stimulation transactivates Protease-Activated Receptor 1 via MMP-13 in heart. Circulation. 2012;125(24):2993-3003. Kamal FA, Smrcka AV, Blaxall BC. Taking the heart failure battle inside the cell: Small molecule targeting of Gβγ subunits. J Mol Cell Cardiol. 2011;51(4):462-7. Ram R, Mickelsen DM, Theodoropoulos C, Blaxall BC. New approaches in small animal echocardiography: imaging the sounds of silence. Amer J Pathol Heart Circ Physiol. 2011;301(5):H1765-80. Belmonte S, Blaxall BC. G-protein coupled receptor kinases as therapeutic targets in cardiovascular disease. Circ Res. 2011;109(3):309-19. Aguilar F, Casey LM, Belmonte S, Noujaim SF, Maekawa N, Dunaevsky O, Protak TL, Noujaim S, Jalife J, Berk BC, Gertler FB, Blaxall BC. Cardiac dysfunction in Mena knockout mice. Amer J Pathol Heart Circ Phys. 2011;300(5):H1841-52. Casey LM, Pistner AR, Belmonte S, Jaffre F, Migdalovic D, Stolpnik O, Nwakanma F, Vorobiof G, Dunaevsky O, Smrcka AV, Blaxall BC. Small molecule targeting of G beta gamma prevents heart failure progression. Circ Res. 2010;107(4):532-9. Jaffré F, Bonnin P, Callebert J, Debbabi H, Setola V, Doly S, Monassier L, Mettauer, Blaxall BC, Launay JM, Maroteaux L. Serotonin and angiotensin receptors in cardiac fibroblasts coregulate adrenergic-dependent cardiac hypertrophy. Circ Res. 2009;104;113-123. Bullard TA, Protack TL, Aguilar F, Bagwe S, Massey HT, Blaxall BC. Identification of Nogo as a novel indicator of heart failure. Physiolog Genom. 2008;32(2):182-9. R, Hampton CR, Casey LM, Bullard TA, Tencati M, Pedersen B, Andrade-Gordon P, Sayen MR, Gottlieb RA, Pohlman TH, Verrier ED, Blaxall BC, Mackman N. Par-1 in Cardiac Remodeling and Heart Failure. Circulation. 2007;116(20):2298-306.
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James D. Gulick, MS
Research Instructor
Academic Information
Instructor, UC Department of Pediatrics
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Specialties
Understanding how certain mutations in contractile protein genes are able to alter the function of the heart
Education and Training
MS: University of Missouri-Columbia, Columbia, Mo, 1983
Publications
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Michalek AJ, Howarth JW, Gulick J, Previs MJ, Robbins J, Rosevear PR, Warshaw DM. Phosphorylation modulates the mechanical stability of the cardiac Myosin-binding protein C motif. Biophys J. 2013 Jan 22;104(2):442-52. Bhuiyan MS, Gulick J, Osinska H, Gupta M, Robbins J. Determination of the critical residues responsible for cardiac myosin binding protein C's interactions. J Mol Cell Cardiol. 2012 Dec;53(6):838-47. Weith AE, Previs MJ, Hoeprich GJ, Previs SB, Gulick J, Robbins J, Warshaw DM. The extent of cardiac myosin binding protein-C phosphorylation modulates actomyosin function in a graded manner. J Muscle Res Cell Motil. 2012 Dec;33(6):449-59. Previs MJ, Previs SB, Gulick J, Robbins J, Warshaw DM. Molecular mechanics of cardiac myosin binding protein C in native thick filaments. Science. 2012 Sept 7; 337 (6099): 1215-8. Weith A, Sadayappan S, Gulick J, Previs MJ, Vanburen P, Robbins J, Warshaw DM. Unique single molecule binding of cardiac myosin binding protein-C to actin and phosphorylation-dependent inhibition of actomyosin motility requires 17 amino acids of the motif domain. J Mol Cell Cardiol. 2012 Jan;52(1):219-27. Tranter M, Liu Y, He S, Gulick J, Ren X, Robbins J, Jones WK, Reineke TM. In vivo delivery of nucleic acids via glycopolymer vehicles affords therapeutic infarct size reduction in vivo. Mol Ther. 2012 Mar;20(3):601-8. Jeyaraj D, Haldar SM, Wan X, McCauley MD, Ripperger JA, Hu K, Lu Y, Eapen BL, Sharma N, Ficker E, Cutler MJ, Gulick J, Sanbe A, Robbins J, Demolombe S, Kondratov RV, Shea SA, Albrecht U, Wehrens XH, Rosenbaum DS, Jain MK. Circadian rhythms govern cardiac repolarization and arrhythmogenesis. Nature. 2012 Mar 1;483(7387):96-9.
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Robert Bruce Hinton, MD
Director, Heart Institute BioRepository (HIBR)
is a pediatric cardiologist who has basic and translational research programs. His laboratory studies the genetic and developmental basis of pediatric heart disease with a focus on cardiovascular malformations and valve disease.
513-636-0389
robert.hinton@cchmc.org
Robert Bruce Hinton, MD
Director, Heart Institute BioRepository (HIBR)
Academic Information
Associate Professor, UC Department of Pediatrics
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Specialties
Clinical InterestsCardiovascular genetics; echocardiography Research InterestsValve and aorta disease using human genetics and molecular developmental biology approaches
Biography
Dr. Hinton graduated from Bucknell University with degrees in Art History and Philosophy. He earned his medical degree from the Medical University of South Carolina in Charleston SC. He completed his pediatric residency training at Memorial Health University Medical Center in Savannah GA and his pediatric cardiology fellowship at Cincinnati Children’s Hospital Medical Center. Dr. Hinton went on to pursue a postdoctoral fellowship in Cardiovascular Genetics and Molecular Cardiology at Cincinnati Children’s. He has been an attending staff member of the Division of Cardiology since 2006. Dr. Hinton’s clinical interests relate to cardiovascular genetics and echocardiography. He is a member of the cardiovascular genetics service, and staffs the echocardiography laboratory. Dr. Hinton’s academic interests focus on translational research efforts using mouse models of human disease to identify new therapeutic targets. Dr. Hinton is a member of the American Academy of Pediatrics, the American Heart Association, the American Society of Bioethics and Humanities, and the American Society of Matrix Biology. He was elected to the Society for Pediatric Research in 2007.
Education and Training
BA: Bucknell University, Lewisburg, PA.
MD: Medical University of South Carolina, Charleston, SC.
Residency: Memorial Health University Medical Center, Savannah, GA.
Fellowship: Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
Fellowship: Cincinnati Children's Research Foundation, Cincinnati, OH.
Certification: Pediatrics, Pediatric Cardiology.
Publications
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Krishnamurthy VK, Opoka A, Kern CB, Guliak F, Narmoneva DA, Hinton RB. Regional Maladaptive Matrix Remodeling and Biomechanical Dysfunction in a Mouse Model of Aortic Valve Disease. Matrix Biology. 2012; 31(3):197-205. PMID: 22265892. Kindel SJ, Miller EM, Gupta R, Cripe LH, Hinton RB, Spicer RL, Towbin JA, Ware SM. Pediatric Cardiomyopathy: Importance of Genetic and Metabolic Evaluation. Journal of Cardiac Failure. 2012; 18(5):396-403. PMID: 22555271. Ryan TD, Ware SM, Lucky AW, Towbin JA, Jefferies JL, Hinton RB. Left Ventricular Noncompaction Cardiomyopathy and Aortopathy in a Patient with Recessive Dystrophic Epidermolysis Bullosa. Circulation Heart Failure. 2012; 5(5):81-82. PMID: 22991407. Georg-Abraham JK, Zimmerman SL, Hinton RB, Marino BS, Witte D, Hopkin RJ. Tetrasomy 15q25-qter Identified with SNP Microarray in a Patient with Multiple Anomalies including Complex Cardiovascular Malformation. American Journal of Medical Genetics. 2012; 158A(8):1971-1976. PMID: 22711292. Hinton RB. Bicuspid Aortic Valve and Thoracic Aortic Aneurysm: Three Patient Populations, Two Disease Phenotypes, One Shared Genotype. Cardiology Research and Practice. 2012. 926975. PMID: 22970404. Krishnamurthy VK, Guliak F, Narmoneva DA, Hinton RB. Regional structure-function relationships in mouse aortic valve tissue. J Biomech. Jan 2011;44(1):77-83. Wirrig EE, Hinton RB, Yutzey KE. Differential expression of cartilage and bone-related proteins in pediatric and adult diseased aortic valves. J Mol Cell Cardiol. Mar 2011;50(3):561-569. Calloway TJ, Martin LJ, Zhang X, Tandon A, Benson DW, Hinton RB. Risk factors for aortic valve disease in bicuspid aortic valve: a family-based study. Am J Med Genet A. May 2011;155A(5):1015-1020. Hinton RB, Yutzey KE. Heart valve structure and function in development and disease. Annu Reb Physiol. Mar 2011;73:29-46. Martin LJ, Hinton RB, Zhang X, Cripe LH, Benson DW. Aorta measurements are heritable and influenced by bicuspid aortic valve. Frontiers in Genetics. 2011;2(61).
Grants
Angiogenesis Inhibition Therapy for Aortic Valve Disease. Principal Investigator. National Center for Research Resources (NIH/NCRR). Jul 2011-Jun 2012. Twist1 regulation of valve progenitors. Co-Investigator. National Heart, Lung and Blood Institute (NIH/NHLBI). Jul 2010-Jun 2015. Trial of Beta Blocker Therapy (Atenolol) vs. Angiotensin II Receptor Blocker Therapy (Losartan). Co-Investigator. National Heart, Lung and Blood Institute (NIH/NHLBI) Pediatric Heart Network. Sept 2006-Aug 2016. Aortic root structure-function relationships in a mouse model of aortic valve disease and aortopathy. Supervisor. American Heart Association, Great Rivers Affiliate. Jul 2011-Jun 2012.
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Jeanne M. James, MD
Associate Professor, UC Department of Pediatrics | Director, Cardiology Fellowship Program | Director, Mouse Echocardiography Core
is a pediatric cardiologist, interested in exploring the pathological processes that lead to abnormal heart function as well as the compensatory phenomena intrinsic to the myocardium that may assist in recovery of function. Visit the James lab site.
513-803-3151
jeanne.james@cchmc.org
Jeanne M. James, MD
Associate Professor, UC Department of Pediatrics | Director, Cardiology Fellowship Program | Director, Mouse Echocardiography Core
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Cardiovascular genetics, echocardiography, congenital heart disease, medical education, molecular cardiology, ventricular remodeling, cardiac hypertrophy. Visit the James Lab.
Biography
Jeanne James, MD, is an Associate Professor of Pediatrics at University of Cincinnati College of Medicine and is currently the Director of the Cardiology Fellowship Training Program at Cincinnati Children's Hospital Medical Center.
A native of West Virginia, Dr. James earned her bachelor and medical degrees from West Virginia University in Morgantown, WV. She completed her pediatric residency and pediatric cardiology fellowship at Vanderbilt University Medical Center in Nashville, TN. Dr. James has been an attending staff member of the Division of Cardiology at Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine since 1995. Dr. James' academic interests are in translational research on heart muscle disease, cardiovascular genetics and echocardiography. She has made numerous scholarly contributions to the field with publications describing both laboratory-based and clinical research. She serves as a grant reviewer for the American Heart Association and is a peer-reviewer for a number of scientific and medical journals. Dr. James has established collaborative relationships with laboratory researchers at Cincinnati Children’s Hospital, the University of Cincinnati College of Medicine and investigators across the United States. As the Director of the Mouse Echocardiography Core, she uses non-invasive imaging to evaluate phenotypes of transgenic mice, including embryonic mice. Dr. James serves as an attending physician in clinical echocardiography laboratory as well as the inpatient cardiology ward and consult team. Dr. James is a member of the Cardiovascular Genetics (CVG) service and has significant responsibilities in the CVG outpatient clinic. Dr. James is a member of the American Society of Echocardiography, the American Heart Association and the Society for Pediatric Research.
Education and Training
MD: West Virginia University, Morgantown, WV, 1987.
Residency: Vanderbilt University Medical Center, Nashville, TN, 1987-90.
Fellowship: Vanderbilt University Medical Center, Nashville, TN, 1991-94.
Certification: Pediatrics, 1990 - present
Certified: Pediatric Cardiology, 1996 - present
Publications
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Pattison J, Waggoner J, James J, Martin L, Gulick J, Osinska H, Klevitsky R, Kranias E, Robbins J. (2008) Phospholamban overexpression in transgenic rabbits. Transgenic Research 17(2):157-70.
Suzuki T, Palmer B, James J, Wang Y, Chen V, VanBuren P, Maughan D, Robbins J, LeWinter M. (2009) Effects of cardiac myosin isoform variation on myofilament function and cross-bridge kinetics in transgenic rabbits. Circ Heart Fail 2(4):334-41.
James J, Hor K, Moga M, Martin L, Robbins J. (2010) Effects of myosin heavy chain manipulation in experimental heart failure. J Mol Cell Cardiol 48(5):999-1006.
Hinton R, Adelman-Brown J, Witt S, Krishnamurthy V, Gruber M, Osinska H, Sakthivel B, James J, Narmoneva D, Mecham R, Benson D. (2010) Elastin haploinsufficiency results in latent progressive aortic valve disease in a mouse model. Circ Res 107(4):549-57.
Acehan D, Vaz F, Houtkooper R, James J, Moore V, Tokunaga C, Kulik W, Wansapura J, Toth M, Strauss A and Khuchua Z. (2010) Cardiac and skeletal muscle defects in a mouse model of human Barth syndrome. J Biol Chem 286(2):899-908.
Stanley BA, Graham DR, James J, Mitsak M, Tarwater PM, Robbins J, Van Eyk JE. (2011) Altered myofilament stoichiometry in response to heart failure in a cardioprotective a-myosin heavy chain transgenic rabbit model. Proteomics Clin Appl 5(3-4):147-58.
James J and Robbins J. (2011) Signaling and myosin binding protein C. J Biol Chem 286(12):9913-9.
Combs M, Braitsch C, Lange A, James J and Yutzey K. (2011) NFATc1 promotes epicardium-derived cell (EPDC) invasion into myocardium. Development 138(9):1747-57.
James J, Kinnett K, Ittenbach R, Wang Y, Benson D and Cripe L. (2011) Electrocardiographic abnormalities in very young Duchenne muscular dystrophy patients precede the onset of cardiac dysfunction. Neuromuscul Disord 21(7):462-7.
Sadayappan S, Gulick J, Martin L, Osinska H, Barefield D, Cuello F, Avkiran M, Lasko V, Lorenz J, Maillet M, Martin J, Heller-Brown J, Bers D, Molkentin J, James J and Robbins J. (2011) A critical function for Ser-282 in cardiac myosin binding protein-C phosphorylation and cardiac function. Circ Res 109(2):141-50.
Cheek J, Wirrig E, Alfieri C, James J and Yutzey K. Differential activation of valvulogenic, chondrogenic and osteogenic pathways in mouse models of myxomatous and calcific aortic valve disease. In press.
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Zaza Khuchua, PhD
Research Associate Professor
research Interests are mitochondrial structure, function, biogenesis and recycling in normal and pathological heart muscle. More specifically we are interested in defects in cardiac lipid and phospholipid metabolism. We employ genetically engineered mice to model human genetic disorders.
513-636-1340
zaza.khuchua@cchmc.org
Zaza Khuchua, PhD
Research Associate Professor
Academic Information
Associate Professor, UC Department of Pediatrics
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Specialties
Mitochondrial function; structure and dynamics in cardiac cells in normal and pathological conditions; role of mitochondrial phospholipids in aerobic metabolism in heart; role of lipid molecules in cell signaling systems
Education and Training
MS: Moscow State University, 1981
PhD: All Union Cardiology Research Center, Moscow Russia, 1987
Publications
View PubMed Publications
Acehan D, Vaz F, Houtkooper RH, James J, Moore V, Tokunaga C, Kulik W, Wansapura J, Toth MJ, Strauss A, Khuchua Z. Cardiac and skeletal muscle defects in a mouse model of human Barth syndrome. J Biol Chem. 2011 Jan 14;286(2):899-908. Acehan D, Khuchua Z, Houtkooper RH, Malhotra A, Kaufman J, Vaz FM, Ren M, Rockman HA, Stokes DL, Schlame M. Distinct effects of Tafazzin deletion in differentiated and undifferentiated mitochondria. Mitochondrion. Tchekneva EE, Khuchua Z, Davis LS, Kadkina V, Dunn SR, Bachman S, Ishibashi K, Rinchik EM, Harris RC, Dikov MM, Breyer MD. Single amino acid substitution in aquaporin 11 causes renal failure. J Am Soc Nephrol. 2008 10:1955-64.
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Marjorie Maillet, PhD
Research Instructor
is interested in understanding the signaling pathways that lead to cardiac hypertrophy and heart disease. Her current projects aim at defining new signaling pathways that regulate calcineurin and NFAT in the heart as well as characterizing MAP kinases targets associated with cardiac hypertrophy and heart failure. Visit the Molkentin lab.
513-636-2467
marjorie.maillet@cchmc.org
Marjorie Maillet, PhD
Research Instructor
Academic Information
University of Cincinnati College of Medicine
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Specialties
Signaling pathways, Cellular Biology, Cardiac Hypertrophy & Heart Failure
Education and Training
PhD, Paris XI University, Orsay, France, 2003 Fellowship, Cincinnati Children’s Hospital, Cincinnati, Ohio
Publications
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van Berlo, J. H., Maillet, M. & Molkentin, J. D. Signaling effectors underlying pathologic growth and remodeling of the heart. J Clin Invest 123, 37-45. 2013. Maillet, M., van Berlo, J. H. & Molkentin, J. D. Molecular basis of physiological heart growth: fundamental concepts and new players. Nat Rev Mol Cell Biol 14, 38-48. 2012. Lynch, J. M., Maillet, M., Vanhoutte, D., Schloemer, A., Sargent, M. A., Blair, N. S., Lynch, K. A., Okada, T., Aronow, B. J., Osinska, H., Prywes, R., Lorenz, J. N., Mori, K., Lawler, J., Robbins, J. & Molkentin, J. D. A thrombospondin-dependent pathway for a protective ER stress response. Cell 149, 1257-68. 2012. Le Grand, F., Grifone, R., Mourikis, P., Houbron, C., Gigaud, C., Pujol, J., Maillet, M., Pages, G., Rudnicki, M., Tajbakhsh, S. & Maire, P. Six1 regulates stem cell repair potential and self-renewal during skeletal muscle regeneration. J Cell Biol 198, 815-32. 2012. Drawnel, F. M., Wachten, D., Molkentin, J. D., Maillet, M., Aronsen, J. M., Swift, F., Sjaastad, I., Liu, N., Catalucci, D., Mikoshiba, K., Hisatsune, C., Okkenhaug, H., Andrews, S. R., Bootman, M. D. & Roderick, H. L. Mutual antagonism between IP(3)RII and miRNA-133a regulates calcium signals and cardiac hypertrophy. J Cell Biol 199, 783-98. 2012. Davis, J., Maillet, M., Miano, J. M. & Molkentin, J. D. Lost in transgenesis: a user's guide for genetically manipulating the mouse in cardiac research. Circ Res 111, 761-77. 2012. Sadayappan, S., Gulick, J., Osinska, H., Barefield, D., Cuello, F., Avkiran, M., Lasko, V. M., Lorenz, J. N., Maillet, M., Martin, J. L., Brown, J. H., Bers, D. M., Molkentin, J. D., James, J. & Robbins, J. A critical function for ser-282 in cardiac Myosin binding protein-C phosphorylation and cardiac function. Circ Res 109, 141-50. 2011. Qian, L., Wythe, J. D., Liu, J., Cartry, J., Vogler, G., Mohapatra, B., Otway, R. T., Huang, Y., King, I. N., Maillet, M., Zheng, Y., Crawley, T., Taghli-Lamallem, O., Semsarian, C., Dunwoodie, S., Winlaw, D., Harvey, R. P., Fatkin, D., Towbin, J. A., Molkentin, J. D., Srivastava, D., Ocorr, K., Bruneau, B. G. & Bodmer, R. Tinman/Nkx2-5 acts via miR-1 and upstream of Cdc42 to regulate heart function across species. J Cell Biol 193, 1181-96. 2011. Kehat I, Davis J, Tiburcy M, Accornero F, Saba-El-Leil MK, Maillet M, York AJ, Lorenz JN, Zimmermann WH, Meloche S, Molkentin JD. Extracellular signal-regulated kinases 1 and 2 regulate the balance between eccentric and concentric cardiac growth. Circ Res. 2011 Jan 21;108(2):176-83. Nakayama H, Bodi I, Maillet M, DeSantiago J, Domeier TL, Mikoshiba K, Lorenz JN, Blatter LA, Bers DM, Molkentin JD. The IP3 receptor regulates cardiac hypertrophy in response to select stimuli. Circ Res. 2010 Sep 3;107(5):659-66
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Jeffery D. Molkentin, PhD
Professor | Howard Hughes Medical Institute Investigator
Academic Information
Professor, UC Department of Pediatrics
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Specialties
Biography
Dr. Molkentin's research aims to understand the intracellular signaling pathways and transcriptional regulatory circuits that control mammalian cell growth and differentiation. His work has advanced the understanding of molecular events behind heart disease and muscular dystrophy. In 2008 he was named a Howard Hughes Medical Institute (HHMI) investigator. For a full description of Dr. Molkentin's work, please see his Faculty Lab Site in the Division of Molecular and Cardiovascular Biology.
Education and Training
BS Marquette University, Milwaukee WI, 1989.
PhD: Medical College of Wisconsin, 1994.
Publications
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Davis J, Burr AR, Davis GF, Birnbaumer L, Molkentin JD. A TRPC6-dependent pathway for myofibroblast transdifferentiation and wound healing in vivo. Dev. Cell 2012. 23:705-715. Auger-Messier M, Accornero F, Goonasekera SA, Bueno OF, Lorenz JN, van Berlo JH, Willette RN, Molkentin JD. Unrestrained p38 MAPK Activation in Dusp1/4 Double Null Mice Induces Cardiomyopathy. Circ Res. 2012. In Press. Lorts A, Schwanekamp JA, Baudino TA, McNally EM, Molkentin JD. Deletion of periostin reduced muscular dystrophy and fibrosis in mice by modulating the transforming growth factor-b pathway. Proc Natl Acad Sci USA. 2012. 109:10978-10983 Lynch JM, Maillet M, Vanhoutte D, Schloemer A, Sargent MA, Blair NS, Lynch KA, Okada T, Aronow BJ, Osinska H, Prywes R, Lorenz JN, Mori K, Lawler J, Robbins J, Molkentin JD. A thrombospondin-dependent pathway for a protective ER stress response. Cell. 2012. 149,1257-1268 Liu Q, Chen Y, Auger-Messier M, Molkentin JD. Interaction Between NFkB and NFAT Coordinates Cardiac Hypertrophy and Pathological Remodeling. Circ Res. 2012. 110:1077-1086 Goonasekera SA, Molkentin JD. Unraveling the secrets of a double life: Contractile versus signaling Ca(2+) in a cardiac myocyte. J Mol Cell Cardiol. 52:317-322. 2012. Goonasekera SA, Hammer K, Auger-Messier M, Bodi I, Chen X, Zhang H, Reiken S, Elrod JW, Correll RN, York AJ, Sargent MA, Hofmann F, Moosmang S, Marks AR, Houser SR, Bers DM, Molkentin JD. Decreased cardiac L-type Ca2+ channel activity induces hypertrophy and heart failure in mice. J. Clin Invest. 2012. 122:280-290
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Enkhsaikhan Purevjav, MD, PhD
Research Assistant Professor
focuses on identifying and screening the potential genes responsible for inherited and acquired cardiac diseases, creating in vitro and in vivo cardiomyopathy models and performing functional studies of mutations identified. Additionally, she studies the effects of factors such as viral infections, drugs (ACE inhibitors and beta-blockers) and mechanical stress (cyclic mechanical stretch, acute and chronic exercise) on cardiac function.
513-803-2576
enkhsaikhan.purevjav@cchmc.org
Enkhsaikhan Purevjav, MD, PhD
Research Assistant Professor
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Cardiac disease; genetic abnormalities; cardiac mechanosensing; cardiomyopathy
Biography
Enkhsaikhan Purejav's, MD, PhD is focused on screening the potential genes responsible for inherited and acquired cardiac diseases and performing functional studies of mutations in these genes by creating in vitro and in vivo models. In addition, she investigates the effects of factors such as viral infections, drugs including ACE inhibitors and beta-blockers, and mechanical stress (cyclic mechanical stretch, acute and chronic exercise) on cardiac function in these models.
Education and Training
MD: Leningrad Pediatric Medical Institute, Russia, 1989 Residency: Saint’s Petersburg Pediatric Medical Academy, Russia Certification: Pediatric Cardiology, 1994 PhD: Shimane Medical University, Japan, 2003
Publications
View PubMed Publications
Purevjav E, Arimura T, Augustin S, Huby AC, Takagi K, Nunoda S, Kearney DL, Taylor MD, Terasaki F, Bos JM, Ommen SR, Shibata H, Takahashi M, Itoh-Satoh M, McKenna WJ, Murphy RT, Labeit S, Yamanaka Y, Machida N, Park JE, Alexander PM, Weintraub RG, Kitaura Y, Ackerman MJ, Kimura A, Towbin JA. Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations. Hum Mol Genet. 2012 May 1;21(9):2039-53. Purevjav E, Varela J, Morgado M, Kearney DL, Li H, Taylor MD, Arimura T, Moncman CL, McKenna W, Murphy RT, Labeit S, Vatta M, Bowles NE, Kimura A, Boriek AM, Towbin JA. Nebulette mutations are associated with dilated cardiomyopathy and endocardial fibroelastosis. J Am Coll Cardiol. 2010 Oct 26;56(18):1493-502. Samani K, Wu G, Ai T, Shuraih M, Mathuria NS, Li Z, Sohma Y, Purevjav E, Xi Y, Towbin JA, Cheng J, Vatta M. A novel SCN5A mutation V1340I in Brugada syndrome augmenting arrhythmias during febrile illness. Heart Rhythm. 2009 Sep;6(9):1318-26. Wu G, Ai T, Kim JJ, Mohapatra B, Xi Y, Li Z, Abbasi S, Purevjav E, Samani K, Ackerman MJ, Qi M, Moss AJ, Shimizu W, Towbin JA, Cheng J, Vatta M. alpha-1-syntrophin mutation and the long-QT syndrome: a disease of sodium channel disruption. Circ Arrhythm Electrophysiol. 2008 Aug;1(3):193-201. Purevjav E, Nelson DP, Varela JJ, Jimenez S, Kearney DL, Sanchez XV, DeFreitas G, Carabello B, Taylor MD, Vatta M, Shearer WT, Towbin JA, Bowles NE. Myocardial Fas ligand expression increases susceptibility to AZT-induced cardiomyopathy. Cardiovasc Toxicol. 2007;7(4):255-63. Hardarson HS, Baker JS, Yang Z, Purevjav E, Huang CH, Alexopoulou L, Li N, Flavell RA, Bowles NE, Vallejo JG. Toll-like receptor 3 is an essential component of the innate stress response in virus-induced cardiac injury. Am J Physiol Heart Circ Physiol. 2007 Jan;292(1):H251-8. Purevjav E, Kimura M, Takusa Y, Ohura T, Tsuchiya M, Hara N, Fukao T, Yamaguchi S. Molecular study of electron transfer flavoprotein alpha-subunit deficiency in two Japanese children with different phenotypes of glutaric acidemia type II. Eur J Clin Invest. 2002 Sep;32(9):707-12.
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Sudarsan Rajan, PhD
has expertise in development of humanized mouse models for cardiovascular research with special focus on contractile and regulatory proteins. He joined the Division of Molecular Cardiovascular Biology with Dr. Robbin’s group to become a part of the ongoing research efforts of the Heart Institute. His current focus extends to understanding molecular mechanisms of the proteotoxicity in heart as well as identifying and exploiting unrecognized pathways in the biology of heart failure. Visit the Robbins lab website.
513-803-7860
sudarsan.rajan@cchmc.org
Sudarsan Rajan, PhD
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Development of humanized mouse models for cardiovascular research and understanding the intracellular signaling pathways; contractile and regulatory protein gene expression and function
Biography
Sudarsan Rajan, PhD, received his doctorate in India and the post-doctoral training in the Department of Molecular Genetics, University of Cincinnati. His expertise has been in development of humanized mouse models for cardiovascular research with special focus on contractile and regulatory proteins. He was selected as one of the three finalists for the Outstanding Early-Career Investigator Award during the AHA-Basic Cardiovascular Sciences 2010 Scientific Sessions: Technological and Conceptual Advances in Cardiovascular Disease. His current research is supported by the National Scientist Development grant from the American Heart Association.
Education and Training
MSc: JIPMER, India, 1994. PhD: Madurai Kamaraj University, India, 2002. Postdoctoral Training: University of Cincinnati, Cincinnati, OH, 2002-2011.
Publications
Rajan S, Jagatheesan G, Karam CN, Alves ML, Bodi I, Schwartz A, Bulcao CF, D'Souza KM, Akhter SA, Boivin GP, Dube DK, Petrashevskaya N, Herr AB, Hullin R, Liggett SB, Wolska B, Solaro RJ, Wieczorek DF. Molecular and Functional Characterization of a Novel Cardiac Specific Human Tropomyosin Isoform. Circulation. 2010;121:410-18. Jagatheesan G, Rajan S, Wieczorek DF. Investigations into tropomyosin function using mouse models. J Mol Cell Cardiol. 2010 May;48(5):893-8. Wieczorek DF, Jagatheesan G, Rajan S. The role of tropomyosin in heart disease. In Tropomyosin (Ed.) Peter Gunning. Adv Exp Med Biol. 2008;644:132-42. Rajan S, Ahmed RP, Jagatheesan G, Petrashevskaya N, Boivin GP, Urboniene D, Arteaga GM, Wolska BM, Solaro RJ, Liggett SB, and Wieczorek DF. Dilated cardiomyopathy mutant tropomyosin mice develop cardiac dysfunction with significantly decreased fractional shortening and myofilament calcium sensitivity. Circ Res. 2007;101(2):205-14. Rajan S, Williams SS, Jagatheesan G, Ahmed RP, Fuller-Bicer G, Schwartz A, Aronow BJ, Wieczorek DF. Microarray analysis of gene expression during early stages of mild and severe cardiac hypertrophy. Physiol Genomics. 2006;27;27(3):309-17. Rajan S, Radhakrishnan J, Rajamanickam C. Direct injection and expression in vivo of full-length cDNA of the cardiac isoform of alpha-2 macroglobulin induces cardiac hypertrophy in the rat heart. Basic Res Cardiol. 2003;98(1):39-49.
Grants
Translational and Post-translational Regulation of Tropomyosin in Normal and Cardiomyopathic Hearts. Principal Investigator. American Heart Association. Jan 2011 - Dec 2014.
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Stephanie M. Ware, MD, PhD, FACMG
Co-Director, Cardiovascular Genetics
is a clinical geneticist who has basic and translational research programs in cardiac structure and function. Her lab studies the genetic and developmental basis of congenital heart defects, with specific interest in the molecular mechanisms controlling heart sidedness in developmental diseases such as X-linked heterotaxy. Translational research in pediatric cardiomyopathy is a second lab focus. Visit the Ware Lab.
513-803-1750
stephanie.ware@cchmc.org
Stephanie M. Ware, MD, PhD, FACMG
Co-Director, Cardiovascular Genetics
Associate Medical Director and Director of Research and Development, The Heart Institute Diagnostic Laboratory
Academic Information
Associate Professor, UC Department of Pediatrics
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Specialties
Clinical genetics; cardiovascular genetics; cardiomyopathy; cardiovascular development
Biography
Stephanie M. Ware, MD, PhD, is an Associate Professor of Pediatrics, University of Cincinnati College of Medicine. She is Co-Director of Cardiovascular Genetics in the Heart Institute as well as Associate Medical Director and Director of Research and Development of the Heart Institute Diagnostic Laboratory. She has a joint academic appointment in the Division of Human Genetics at Cincinnati Children’s Hospital. Dr. Ware graduated Summa cum laude with highest honors in Zoology from Butler University. She earned her MD and PhD degrees at the University of Cincinnati College of Medicine where she was elected to Alpha Omega Alpha Honor Society. She completed her pediatric residency and clinical genetics fellowship at Baylor College of Medicine in Houston, Texas. Dr. Ware’s research interests include the genetic and developmental basis of disorders of cardiac structure and function. Her research laboratory has made significant contributions in the areas of congenital heart defects and cardiomyopathy. Dr. Ware has received a number of scholarly awards including the Weinstein Cardiovascular Development Young Investigator Award, the March of Dimes Research Foundation Basil O’Connor Scholar Award, and the Burroughs Wellcome Clinical Scientist in Translational Research Award. She holds numerous grants and is currently Co-Chair of the American Heart Association Cardiovascular Development study section. In 2011, she was elected as the National Council Member Representing Genetics for the Society of Pediatric Research. Clinically, Dr. Ware evaluates and manages patients with genetic disorders and has specific expertise in cardiomyopathy and syndromes with cardiovascular disease. Dr. Ware is a member of the American Heart Association, the American Society for Human Genetics, the Society for Pediatric Research, and is Faculty of the American College of Medical Genetics. Visit Dr. Ware's Lab site.
Education and Training
MD, PhD: University of Cincinnati College of Medicine, Cincinnati, OH,1997. Residency: Pediatrics, Baylor College of Medicine, 2002. Fellowship: Medical Genetics, Baylor College of Medicine, 2002. American Board of Pediatrics, 2000, 2007. American Board of Medical Genetics in Clinical Genetics, 2002.
Publications
View PubMed Publications
Tariq M, Belmont JW, Lalani S, Smolarek T, Ware SM. SHROOM3 is a novel candidate for heterotaxy identified by whole exome sequencing. Genome Biol. 2012. Epub ahead of print. Bedard JEJ, Haaning AM, Ware SM. Identification of a novel ZIC3 isoform and mutation screening in patients with heterotaxy and congenital heart disease patients. PLoS One. 2011;6(8):e23755. Czosek RJ, Haaning A, Ware SM. A mouse model of conduction system patterning abnormalities in heterotaxy syndrome. Pediatr Res. 2010;68:275-280. Sutherland M, Ware SM. Disorders of left-right asymmetry: heterotaxy and situs inversus. Am J Med Genet C Semin Med Genet. 2009 Nov 15;151C(4):307-17. Ware SM*, El-Hassan N, Kahler SG, Zhang Q, Ma Y-M, Miller E, Wong B, Spicer RL, Craigen WJ, Kozel BA, Grange DK, Wong L-J. Infantile cardiomyopathy caused by a mutation in the overlapping region of mitochondrial ATPase 6 and 8 genes. J Med Genet. 2009;46: 308-314. *corresponding author Kogan JM, Miller E, Ware SM. High resolution SNP based microarray mapping of mosaic supernumerary marker chromosomes 13 and 17: delineating novel loci for apraxia. Am J Med Genet. 2009;149A: 887-893. Mohapatra B, Casey B, Li H, Ho-Dawson T, Smith L, Fernbach SD, Molinari L, Niesh SR, Jefferies JL, Craigen WJ, Towbin JA, Belmont JW, Ware SM. Identification and functional characterization of NODAL rare variants in heterotaxy and isolated cardiovascular malformations. Hum Mol Genet. 2009;18: 861-871. Ware SM*, Quinn M, Ballard ET, Miller E, Uzark K, Spicer RL. Pediatric restrictive cardiomyopathy associated with a mutation in beta-myosin heavy chain. Clin Genet. 2008;73: 165-170. *corresponding author Bedard JEJ, Purnell JD, Ware SM. Nuclear import and export signals are essential for proper cellular trafficking and function of ZIC3. Hum Mol Genet. 2007;16: 187-198. Ware SM, Harutyunyan KG, Belmont JW. Heart defects in X linked heterotaxy: evidence for a genetic interaction of Zic3 with the Nodal signaling pathway. Dev Dyn. 2006 Jun;235:1631-1637.
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Joshua S. Waxman, PhD
Assistant Professor
Academic Information
Assistant Professor, UC Department of Pediatrics
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Specialties
Understanding the molecular underlying nature of congenital heart defects; cardiomyocyte formation Visit the Waxman Lab.
Education and Training
BA: New College, Sarasota, FL,1999.
PhD: University of Washington, Seattle, WA, 2004.
Postdoctoral Fellow: Skirball Institute/NYU School of Medicine, New York, NY, 2004-2009.
Publications
View PubMed Publications
Dohn TE, Waxman JS. Distinct phases of Wnt/β-catenin signaling direct cardiomyocyte formation in zebrafish. Dev Biol. Epub ahead of print. Nov 4, 2011. Sorrell MR, Waxman JS. Restraint of Fgf8 signaling by retinoic acid signaling is required for proper heart and forelimb formation. Dev. Biol. Oct 1, 2011. ;358(1):44-55. Epub Jul 22, 2011. Waxman JS, Yelon D. Zebrafish retinoic acid receptors function as context-dependent transcriptional activators. Dev Biol. 2011;352:128-40.
Feng L, Hernandez RE, Waxman JS, Yelon D, Moens CB. Dhrs3a regulates retinoic acid biosynthesis through a feedback inhibition mechanism. Dev Biol. 2010 Feb 1;338(1):1-14. Waxman JS, Yelon D. Increased Hox activity mimics the teratogenic effects of excess retinoic acid signaling. Developmental Dynamics. 2009;238:1207-13.
Linville A, Radkte K, Waxman JS, Yelon D, Schilling T. Combinatorial roles for zebrafish retinoic acid receptors in the hindbrain, limbs and pharyngeal arches. Developmental Biology. 2009;325:60-70.
Waxman JS, Keegan BR, Roberts RW, Poss KD, Yelon D. Hoxb5b acts downstream of retinoic acid signaling in the forelimb field to restrict cardiac cell number in zebrafish. Developmental Cell. 2008;15:923-34.
Waxman JS, Yelon D. Comparison of the expression patterns of newly identified zebrafish retinoic acid and retinoid X receptors. Developmental Dynamics. 2007;236:587-95.
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Katherine Yutzey, PhD
Professor
is focused on the molecular mechanisms of heart development and disease. Particular emphasis is on signaling pathways and transcription factors that control heart valve development as well as contribute to pediatric and adult valve disease. Additional projects address the development of coronary vasculature, cardiac fibrosis and maturation of cardiac muscle after birth. Visit the Yutzey Lab.
513-636-8340
katherine.yutzey@cchmc.org
Katherine Yutzey, PhD
Professor
Academic Information
Professor, UC Department of Pediatrics
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Specialties
Molecular regulation of heart development; valve development and disease mechanisms; cardiomyocyte proliferation, cardiac connective tissue lineages. Visit the Yutzey Lab.
Biography
Visit Dr. Yutzey's Lab Web Site. Katherine E. Yutzey, PhD, professor, joined the Division of Molecular Cardiovascular Biology at Cincinnati Children's Hospital Medical Center in 1995. Dr. Yutzey is the first recipient of the Fifth Third Bank/Charlotte R. Schmidlapp Women Scholars Award and was also a recipient of a Children's Hospital Medical Center Trustee Award. Her work is also supported by grants from National Institutes of Health (NIH) and the American Heart Association. The focus of Dr. Yutzey's research program is the regulation of normal and abnormal heart development. Congenital heart defects represent one of the most common classes of human birth defects. Increasing evidence exists for a genetic basis of certain instances of congenital heart disease. Dr. Yutzey’s lab also studies molecular mechanisms of cardiac connective tissue cell lineage development and disease. This work focuses on heart valve development and disease as well as mechanisms of cardiac fibrosis.
Education and Training
BA: Oberlin College, Oberlin, OH, 1986. PhD: Purdue University, West Lafayette, IN,1992 Fellowship: Cornell University Medical College, New York, NY,1992-1995.
Publications
View PubMed Publications
Sengupta, A. V.V. Kalinichenko, K.E. Yutzey. FoxO and FoxM1 transcription factors have antagonistic functions in neonatal cardiomyocyte cell cycle withdrawal and IGF1 gene regulation. Circ. Res. 112:267-277. 2013. Carruthers, C.A., C.M. Alfieri, E.M. Joyce, S.C. Watkins, K.E. Yutzey, M.S. Sacks Gene expression and collagen fiber micromechanical interactions of the semilunar heart valve interstitial cell. Cell. Mol. Bioeng. 5:254-265. Mead TJ, Yutzey KE. Notch pathway regulation of neural crest cell development in vivo. Dev. Dyn. 2012:241:376-389. Chakraborty S, Yutzey KE.Tbx20 regulation of cardiac cell proliferation and lineage specialization during embryonic and fetal development in vivo. Dev. Biol. 2012:363:234-246. Cheek JD, Wirrig EE, Alfieri CM, James JF, Yutzey KE. Differential activation of valvulogenic, chondrogenic and osteogenic pathways in mouse models of myxomatous and calcific aortic valve disease. J. Mol. Cell. Cardiol. 2012:52:689-700. Le TT, Conley KW, Mead TJ, Rowan S, Yutzey KE, Brown NL. Requirements for Jag1-Rbpj mediated Notch signaling during early mouse lens development. Dev. Dyn. 2012:241:493-504. Sengupta A, Chakraborty S, Paik J, Yutzey KE, and Evans-Anderson HJ. FoxO1 is required in endothelial but not myocardial cell lineages during cardiovascular development. Dev. Dyn. 2012:241:803-813. Fujimoto KL, Tobita K, Guan J, Hashizume R, Takanari K, Alfieri CM, Yutzey KE, Wagner WR. Placement of an elastic biodegradable cardiac patch on a subacute infarcted heart leads to cellularization with early developmental cardiomyocyte characteristics. J. Card. Fail. 2012:18:585-595. Braitsch CM, Combs MD, Quaggin SE, Yutzey KE. Pod1/Tcf21 is regulated by retinoic acid signaling and inhibits differentiation of epicardium derived cells into smooth muscle in the developing heart. Dev. Biol. 2012:368:345-357. Hinton RB,Yutzey KE. Heart valve structure and function in development and disease. Ann Rev. Physiol. 2011:73:29-36.
Grants
The Akt/FoxO pathway in heart development.
Component Principal Investigator.
National Institutes of Health.
#P01 HL069779.
2002-2012 Twist1 regulation of valve progenitors.wist1 regulation of valve.
National Institutes of Health.
R01 HL082716.
2010-2015 Wnt signaling in heart valve development and disease.
Principal Investigator.
National Institutes of Health
#R01 HL094319
2012-2016 Cell signaling mechanisms of calcific aortic valve disease.
Principal Investigator.
National Institutes of Health.
#R01 HL114682
2012-2016 Trainee supportDifferential Twist1 dimer function and gene regulation in valve progenitor cells.
Mary Lee, Fellow. K. Yutzey,
Sponsor. American Heart Association-Great Rivers Affiliate,
Pre-doctoral Fellowship
2011-2013 FOXO function in cardiomyocytes during development and disease.
Arunima Sengupta, Fellow. K. Yutzey,
Sponsor. American Heart Association-Great Rivers Affiliate
Post-doctoral Fellowship
2011-2013 Summer Undergraduate Research Fellowship (SURF).
K. Yutzey, Principal Investigator.
American Heart Association-Great Rivers Affiliate.
2012-2013 The role of COX2 in the progression of human and mouse aortic valve disease.
Elaine Wirrig, Fellow. K Yutzey,
Sponsor. NIH NHLBI Post-Doctoral Fellowship
(F32 HL110390).
2012-2014
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