Molecular Cardiovascular Biology

Research Faculty

A photo of Jeffrey Robbins.

Jeffrey Robbins, PhD Executive Co-Director, Heart Institute

Jeffrey Robbins, PhD, established the means to direct the heart to synthesize normal and mutant proteins. They can turn these on and off at will and this allows them to establish cause-and-effect relationships between mutant proteins and the development of cardiac disease. The lab is particularly interested in how protein aggregation can cause cardiac disease but also studies the contractile protein mutations that cause hypertrophic cardiomyopathy and heart failure.
Visit the Robbins Lab.

513-636-8098 jeffrey.robbins@cchmc.org

A photo of Jeffrey Robbins.

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Jeffrey Robbins, PhD

Executive Co-Director, Heart Institute

Director, Molecular Cardiovascular Biology

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-8098

Email jeffrey.robbins@cchmc.org

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Structure function relationships for the contractile proteins; cardiac-specific gene manipulation in transgenic rabbits; the contractile protein myosin and human heart failure; molecular studies of human valve disease

Visit the Robbins Lab.

Jeff Robbins CV (.pdf)

Gupta MK, Robbins J. Post-translational control of cardiac hemodynamics through myosin binding protein C. Pflugers Arch: European journal of physiology. 2014 Feb;466(2):231-6.

Mun JY, Previs MJ, Yu HY, Gulick J, Tobacman LS, Beck Previs S, Robbins J, Warshaw DM, Craig R. Myosin-binding protein C displaces tropomyosin to activate cardiac thin filaments and governs their speed by an independent mechanism. Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2170-5.

Sandri M, Robbins J. Proteotoxicity: An underappreciated pathology in cardiac disease. J Mol Cell Cardiol. 2014 Jun;71c:3-10.

Wang X, Robbins J. Proteasomal and lysosomal protein degradation and heart disease. J Mol Cell Cardiol. 2014 Jun;71c:16-24.

James J, Robbins J. Ablating a cardiac protein: Causality at last. Circ Res. 2013;112:1415-1419.

Razzaque MA, Gupta M, Osinska H, Gulick J, Blaxall BC, Robbins J. An endogenously produced fragment of cardiac myosin-binding protein C is pathogenic and can lead to heart failure. Circ Res. 2013 Aug 16;113(5):553-61.

Gupta MK, Gulick J, James J, Osinska H, Lorenz JN, Robbins J. Functional dissection of myosin binding protein C phosphorylation. J Mol Cell Cardiol. 2013;64C:39-50.

Bhuiyan MS, Pattison JS, Osinska H, James J, Gulick J, McLendon PM, Hill JA, Sadoshima J, Robbins J. Enhanced autophagy ameliorates cardiac proteinopathy. J Clin Invest. 2013;123(12):5284-97.

Pattison JS, Robbins J. Desmin and heart disease. In: Kavallaris M, ed. Cytoskeleton and human disease. New York, NY: Humana Press; 2012:411-424.

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;53:838-847.

Cardiac Signaling in the Normal and Abnormal Heart. Principal Investigator. National Heart, Lung, and Blood Institute. Sep 2013-May 2018. #P01 HL69779.

Proteotoxicity: an underappreciated factor in cardiac disease. North American Coordinator. Leducq Transatlantic Alliance For Cardiovascular Disease. 2011-2016.

A photo of Burns Blaxall.

Burns C. Blaxall, PhD, FAHA, FACC, FAPS Director of Translational Science, Heart Institute

Burns C. Blaxall, PhD, FAHA, FACC, FAPS, 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

A photo of Burns Blaxall.

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Burns C. Blaxall, PhD, FAHA, FACC, FAPS

Director of Translational Science, Heart Institute

Co-Director, Heart Institute Research Core & Biorepository

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-803-4005

Email burns.blaxall@cchmc.org

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Molecular and signaling mechanisms of heart failure; cardiac fibrosis; drug and therapeutic discovery

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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.

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Kamal FA, Mickelsen DM, Wegman KM, Travers JG, Moalem J, Hammes SR, Smrcka AV, Blaxall BC. Simultaneous adrenal and cardiac g-protein-coupled receptor-gβγ inhibition halts heart failure progression. J Am Coll Cardiol. 2014;63(23):2549-57.

Ram R, Wescott AP, Varandas K, Dirksen RT, Blaxall BC. Mena associates with Rac1 and modulates connexin 43 remodeling in cardiomyocytes. Am J Physiol Heart Circ Physiol. 2014;306(1):H154-9.

Belmonte SL, Ram R, Mickelsen DM, Gertler FB, Blaxall BC. Cardiac overexpression of Mammalian enabled (Mena) exacerbates heart failure in mice. Am J Physiol Heart Circ Physiol. 2013;305(6):H875-84.

Martin ML, Blaxall BC. Cardiac intercellular communication: are myocytes and fibroblasts fair-weather friends? J Cardiovasc Transl Res. 2012;5(6):768-82.

Aguilar F, Belmonte SL, Ram R, Noujaim SF, Dunaevsky O, Protack TL, Jalife J, Todd Massey H, Gertler FB, Blaxall BC. Mammalian enabled (Mena) is a critical regulator of cardiac function. Am J Physiol Heart Circ Physiol. 2011;300(5):H1841-52.

Belmonte S, Blaxall BC. G-protein coupled receptor kinases as therapeutic targets in cardiovascular disease. Circ Res. 2011;109(3):309-19.

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.

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.

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.

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.

A photo of James D. Gulick.

James D. Gulick, MS

James D. Gulick, MS, is a member of the Robbins Lab, studying cardiac structure and function. His interest lies primarily in understanding how certain mutations in contractile protein genes are able to alter the function of the heart.
Visit the Robbins Lab.

513-803-0994 james.gulick@cchmc.org

A photo of James D. Gulick.

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James D. Gulick, MS

Academic Affiliations

Instructor, UC Department of Pediatrics

Phone 513-803-0994

Fax 513-636-5958

Email james.gulick@cchmc.org

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Research Interests

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

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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.

A photo of Zaza Khuchua.

Zaza Khuchua, PhD

Zaza Khuchua, PhD, 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

A photo of Marjorie Maillet.

Marjorie Maillet, PhD

Marjorie Maillet, PhD, 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

A photo of Marjorie Maillet.

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Marjorie Maillet, PhD

Academic Affiliations

Instructor, UC Department of Pediatrics

Phone 513-636-2467

Email marjorie.maillet@cchmc.org

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Signaling pathways; cellular biology; cardiac hypertrophy and heart failure

Education and Training

PhD: Paris XI University, Orsay, France, 2003.

Fellowship: Cincinnati Children’s Hospital, Cincinnati, Ohio.

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van Berlo JH, Maillet M, Molkentin JD. Signaling effectors underlying pathologic growth and remodeling of the heart. J Clin Invest. 123, 37-45. 2013.

Maillet M, van Berlo JH, Molkentin JD. Molecular basis of physiological heart growth: fundamental concepts and new players. Nat Rev Mol Cell Biol. 14, 38-48. 2012.

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. 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 FM, Wachten D, Molkentin JD, Maillet M, Aronsen JM, Swift F, Sjaastad I, Liu N, Catalucci D, Mikoshiba K, Hisatsune C, Okkenhaug H, Andrews SR, Bootman MD, Roderick HL. 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 JM, Molkentin JD. 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 VM, Lorenz JN, Maillet M, Martin JL, Brown JH, Bers DM, Molkentin JD, 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 JD, Liu J, Cartry J, Vogler G, Mohapatra B, Otway RT, Huang Y, King IN, Maillet M, Zheng Y, Crawley T, Taghli-Lamallem O, Semsarian C, Dunwoodie S, Winlaw D, Harvey RP, Fatkin D, Towbin JA, Molkentin JD, Srivastava D, Ocorr K, Bruneau BG, 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

A photo of Douglas Millay.

Douglas Millay , PhD

Douglas Millay, PhD, is interested in understanding how precursor cells fuse to form multi-nucleated skeletal muscle. We recently discovered a necessary component (named myomaker) of the muscle fusion machinery. The lab's goal is to delineate the mechanisms by which this multi-pass membrane protein directs cell-cell fusion and manipulate muscle cell fusion as a strategy for in vivo cell therapy.
Visit the Millay Lab.

513-803-7437 douglas.millay@cchmc.org

A photo of Douglas Millay.

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Douglas Millay , PhD

Academic Affiliations

Assistant Professor, UC Department of Pediatrics

Phone 513-803-7437

Email douglas.millay@cchmc.org

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Research Interests

Visit the Millay Lab.

Education and Training

BS: Northern Kentucky University, Highland Heights, KY, 2002.

PhD: University of Cincinnati, Cincinnati, OH, 2008.

Fellowship: University of Texas Southwestern, Dallas, TX, 2014.

View PubMed Publications

Millay DP, O’Rourke JR, Sutherland LB, Bezprozvannaya S, Shelton JM, Bassel-Duby R, Olson EN. Myomaker is a membrane activator of myoblast fusion and muscle formation. Nature. 2013 Jul 18;499 (7458).

Millay DP, Olson EN. Making muscle or mitochondria by selective splicing of PGC1α. Cell Metab. 2013 Jan 8;17(1):3-4.

Hatley ME, Tang W, Garcia MR, Finkelstein D, Millay DP, Liu N, Graff J, Galindo RL, Olson EN. A mouse model of rhabdomyosarcoma originating from the adipocyte lineage. Cancer Cell. 2012 Oct 16;22 (4): 536-46.

Zeve D, Seo J, Suh JM, Stenesen D, Tang W, Berglund ED, Wan Y, Williams LJ, Lim A, Martinez MJ, McKay RM, Millay DP, Olson EN, Graff JM. Wnt signaling activation in adipose progenitors promotes insulin-independent muscle glucose uptake. Cell Metab. 2012 Apr 4;15(4):492-504.

Pei J, Millay DP, Olson EN, Grishin NV. CREST--a large and diverse superfamily of putative transmembrane hydrolases. Biol Direct. 2011 Jul 6;6:37.

Goonasekera SA, Lam CK, Millay DP, Sargent MA, Hajjar RJ, Kranias EG, Molkentin JD. Mitigation of muscular dystrophy in mice by SERCA overexpression in skeletal muscle. J Clin Invest. 2011 Mar;121(3):1044-52.

Wissing ER, Millay DP, Vuagniaux G, Molkentin JD. Debio-025 is more effective that prednisone in reducing muscular pathology in mdx mice. Neuromuscul Disord. 2010 Nov;20(11):753-60.

Millay DP, Goonasekera SA, Sargent MA, Molkentin JD. Calcium influx is sufficient to induce muscular dystrophy through a TRPC-dependent mechanism. Proc Natl Acad Sci USA. 2009 Nov 10;106(45)19023-8.

Millay DP, Sargent MA, Roche JA, Maillet M, McNally EM, Bloch RJ, Molkentin JD. Genetic manipulation of dysferlin expression in skeletal muscle: Novel insights into muscular dystrophy. Am J Pathol. 2009 Nov;175(5):1817-23.

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 Apr;14(4):442-7.

A photo of Jeffery Molkentin.

Jeffery D. Molkentin, PhD Professor | Howard Hughes Medical Institute Investigator

Jeffery D. Molkentin, PhD, is interested in understanding the intracellular signaling pathways and transcriptional regulatory circuits that control mammalian cell growth and differentiation.
Visit the Molkentin Lab.

513-636-3557 jeff.molkentin@cchmc.org

A photo of Joshua Waxman.

Joshua S. Waxman, PhD

Joshua S. Waxman, PhD, uses genetic, molecular and cellular biological techniques to understand the underlying mechanisms of congenital heart defects and cardiomyocyte formation during development.
Visit the Waxman Lab.

513-636-7232 joshua.waxman@cchmc.org

A photo of Katherine Yutzey.

Katherine Yutzey, PhD

Katherine Yutzey, PhD, 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.

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513-636-8340 katherine.yutzey@cchmc.org

A photo of Katherine Yutzey.

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Katherine Yutzey, PhD

Academic Affiliations

Professor, UC Department of Pediatrics

Phone 513-636-8340

Fax 513-636-5958

Email katherine.yutzey@cchmc.org

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Molecular regulation of heart development; valve development and disease mechanisms; cardiomyocyte proliferation; cardiac connective tissue lineages.

Visit the Yutzey Lab.

Visit Dr. Yutzey's lab website.

Katherine E. Yutzey, PhD, is a professor who joined the Division of Molecular Cardiovascular Biology at Cincinnati Children's Hospital Medical Center within the University of Cincinnati College of Medicine 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.

View PubMed Publications

Wirrig EE, Hinton RB, Gomez MV, Yutzey KE. Cox2 inhibition reduces aortic valve calcification in vivo. Arterioscler. Thromb Vasc Biol. 2015;35:938-947.

Yutzey KE. Neuregulin1 makes heart muscle. Nature. 2015;520:445-446.

Wirrig EE, Yutzey KE. Conserved transcriptional regulatory mechanisms in aortic valve development and disease. Arterioscler Thromb Vasc Biol. 2014;34:737-741.

Cole CR, Yutzey KE, Brar AK, Goessling LS, vanVickle-Chavez SJ, Cunningham MV, Eghtesady P. Congenital heart disease linked to maternal autoimmunity against cardiac myosin. J Immunol. 2014;192:4074-4082.

Yutzey KE. Cardiovascular Biology: Switched at birth. Nature. 2014;509:572-573.

Yutzey KE, Demer LL, Body SC, Huggins GS, Towler DA, Giachelli CM, Hofmann-Bowman MA, Mortlock DP, Rogers MB, Sadeghi MM, Aikawa E. Calcific aortic valve disease: A consensus summary from the Alliance of Investigators on Calcific Aortic Valve Disease. Arterioscler Thromb Vasc Biol. 2014;34:2387-2393.

Lee MP, Ratner N, Yutzey KE. Genome-wide Twist1 occupancy in endocardial cushion cells, embryonic limb buds and peripheral nerve sheath tumor cells. BMC Genomics. 2014;15:821.

Godby RC, Munjal C, Opoka AM, Smith JM, Yutzey KE, Narmoneva DA, Hinton RB. Cross talk between NOTCH signaling and biomechanics in human aortic valve disease pathogenesis. J Cardiovasc Dev Dis. 2014;1:237-256.

Fang M, Alfieri CM, Hulin A, Conway SJ, Yutzey KE. Loss of -catenin promotes chondrogenic differentiation of aortic valve interstitial cells. Arterioscler Thromb Vasc Biol. 2014;34:2601-2608.

Sengupta A, Kalinichenko VV, Yutzey KE. FoxO and FoxM1 transcription factors have antagonistic functions in neonatal cardiomyocyte cell cycle withdrawal and IGF1 gene regulation. Circ Res. 2013;112:267-277.

Wnt/-catenin signaling and cardiac fibrosis. National Institutes of Health Component Principal Investigator. 2002-2018. P01 HL069779.

Wnt signaling in heart valve development and disease. National Institutes of Health. Principal Investigator. 2012-2016. R01 HL094319.

Cell signaling mechanisms of calcific aortic valve disease. National Institutes of Health. Principal Investigator. 2012-2016. R01 HL114682.

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