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Heart, Lung and Vascular Institute

Sakthivel Sadayappan, Ph.D., M.B.A.

Professor, Department of Internal Medicine; Division of Cardiovascular Health and Disease; Director of Heart Branch of the UC Heart, Lung and Vascular Institute

Research/Clinical Interests

The long-term goal of the Sadayappan Lab involves 1) elucidating the causes of muscle-specific diseases at the molecular level and 2) identifying therapeutic targets that will lead to the development of effective cures. The more specific objectives involve determining the up- and downstream regulators of sarcomere structure and function of both cardiac and skeletal muscles in health and disease.

Contact Information
  • Cardiovascular Center, Room 4935, 4th Floor
  • 231 Albert Sabin Way
  • M.L. 0575
  • Cincinnati, Ohio 45267-0542
  • Office 513-558-7498
  • Fax 513-558-2884
  • Email sadayasl@uc.edu

Peer Reviewed Publications

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Grimes, Kelly M; Barefield, David Y; Kumar, Mohit; McNamara, James W; Weintraub, Susan T; de Tombe, Pieter P; Sadayappan, Sakthivel; Buffenstein, Rochelle 2017. The naked mole-rat exhibits an unusual cardiac myofilament protein profile providing new insights into heart function of this naturally subterranean rodent. Pflugers Archiv : European journal of physiology, ,

Lin, Brian Leei; Song, Taejeong; Sadayappan, Sakthivel 2017. Myofilaments: Movers and Rulers of the Sarcomere. Comprehensive Physiology, 7 2, 675-692

Lynch, Thomas L; Kuster, Diederik W D; Gonzalez, Beverly; Balasubramanian, Neelam; Nair, Nandini; Day, Sharlene; Calvino, Jenna E; Tan, Yanli; Liebetrau, Christoph; Troidl, Christian; Hamm, Christian W; Güçlü, Ahmet; McDonough, Barbara; Marian, Ali J; van der Velden, Jolanda; Seidman, Christine E; Huggins, Gordon S; Sadayappan, Sakthivel 2017. Cardiac Myosin Binding Protein-C Autoantibodies are Potential Early Indicators of Cardiac Dysfunction and Patient Outcome in Acute Coronary Syndrome. JACC. Basic to translational science, 2 2, 122-131

Tong, Carl W; Dusio, Giuseppina F; Govindan, Suresh; Johnson, Dustin W; Kidwell, David T; De La Rosa, Lisa M; Rosas, Paola C; Liu, Yang; Ebert, Elizabeth; Newell-Rogers, M Karen; Michel, Jeffrey B; Trzeciakowski, Jerome P; Sadayappan, Sakthivel 2017. Usefulness of Released Cardiac Myosin Binding Protein-C as a Predictor of Cardiovascular Events. The American journal of cardiology, 120 9, 1501-1507

Barefield, David Y; Lynch, Thomas L; Jagadeesan, Aravindakshan; Sanagala, Thriveni; Sadayappan, Sakthivel 2016. High-Throughput Diagnostic Assay for a Highly Prevalent Cardiomyopathy-Associated MYBPC3 Variant. Journal of molecular biomarkers & diagnosis, 7 6,

Hoffman, Matthew P; Taylor, Erik N; Aninwene, George E; Sadayappan, Sakthivel; Gilbert, Richard J 2016. Assessing the multiscale architecture of muscular tissue with Q-space magnetic resonance imaging: Review. Microscopy research and technique, ,

Kraker, Jessica; Viswanathan, Shiv Kumar; Knöll, Ralph; Sadayappan, Sakthivel 2016. Recent Advances in the Molecular Genetics of Familial Hypertrophic Cardiomyopathy in South Asian Descendants. Frontiers in physiology, 7 , 499

Lipps, Christoph; Nguyen, Jenine H; Pyttel, Lukas; Lynch, Thomas L; Liebetrau, Christoph; Aleshcheva, Ganna; Voss, Sandra; Dörr, Oliver; Nef, Holger M; Möllmann, Helge; Hamm, Christian W; Sadayappan, Sakthivel; Troidl, Christian 2016. N-terminal fragment of cardiac myosin binding protein-C triggers pro-inflammatory responses in vitro. Journal of molecular and cellular cardiology, 99 , 47-56

Lynch, Thomas L; Ismahil, Mohamed Ameen; Jegga, Anil G; Zilliox, Michael J; Troidl, Christian; Prabhu, Sumanth D; Sadayappan, Sakthivel 2016. Cardiac inflammation in genetic dilated cardiomyopathy caused by MYBPC3 mutation. Journal of molecular and cellular cardiology, 102 , 83-93

Stathopoulou, Konstantina; Wittig, Ilka; Heidler, Juliana; Piasecki, Angelika; Richter, Florian; Diering, Simon; van der Velden, Jolanda; Buck, Friedrich; Donzelli, Sonia; Schröder, Ewald; Wijnker, Paul J M; Voigt, Niels; Dobrev, Dobromir; Sadayappan, Sakthivel; Eschenhagen, Thomas; Carrier, Lucie; Eaton, Philip; Cuello, Friederike 2016. S-glutathiolation impairs phosphoregulation and function of cardiac myosin-binding protein C in human heart failure. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 30 5, 1849-64

Taylor, Erik N; Hoffman, Matthew P; Barefield, David Y; Aninwene, George E; Abrishamchi, Aurash D; Lynch, Thomas L; Govindan, Suresh; Osinska, Hanna; Robbins, Jeffrey; Sadayappan, Sakthivel; Gilbert, Richard J 2016. Alterations in Multi-Scale Cardiac Architecture in Association With Phosphorylation of Myosin Binding Protein-C. Journal of the American Heart Association, 5 3, e002836

Barefield, David; Kumar, Mohit; Gorham, Joshua; Seidman, Jonathan G; Seidman, Christine E; de Tombe, Pieter P; Sadayappan, Sakthivel 2015. Haploinsufficiency of MYBPC3 exacerbates the development of hypertrophic cardiomyopathy in heterozygous mice. Journal of molecular and cellular cardiology, 79 , 234-43

Kumar, Mohit; Govindan, Suresh; Zhang, Mengjie; Khairallah, Ramzi J; Martin, Jody L; Sadayappan, Sakthivel; de Tombe, Pieter P 2015. Cardiac Myosin-binding Protein C and Troponin-I Phosphorylation Independently Modulate Myofilament Length-dependent Activation. The Journal of biological chemistry, 290 49, 29241-9

Kuster, Diederik W D; Govindan, Suresh; Springer, Tzvia I; Martin, Jody L; Finley, Natosha L; Sadayappan, Sakthivel 2015. A hypertrophic cardiomyopathy-associated MYBPC3 mutation common in populations of South Asian descent causes contractile dysfunction. The Journal of biological chemistry, 290 9, 5855-67

Lee, Kyounghwan; Harris, Samantha P; Sadayappan, Sakthivel; Craig, Roger 2015. Orientation of myosin binding protein C in the cardiac muscle sarcomere determined by domain-specific immuno-EM. Journal of molecular biology, 427 2, 274-86

Lynch, Thomas L; Sivaguru, Mayandi; Velayutham, Murugesan; Cardounel, Arturo J; Michels, Michelle; Barefield, David; Govindan, Suresh; dos Remedios, Cristobal; van der Velden, Jolanda; Sadayappan, Sakthivel 2015. Oxidative Stress in Dilated Cardiomyopathy Caused by MYBPC3 Mutation. Oxidative medicine and cellular longevity, 2015 , 424751

Thoonen, Robrecht; Giovanni, Shewit; Govindan, Suresh; Lee, Dong I; Wang, Guang-Rong; Calamaras, Timothy D; Takimoto, Eiki; Kass, David A; Sadayappan, Sakthivel; Blanton, Robert M 2015. Molecular Screen Identifies Cardiac Myosin-Binding Protein-C as a Protein Kinase G-I? Substrate. Circulation. Heart failure, 8 6, 1115-22

Tong, Carl W; Wu, Xin; Liu, Yang; Rosas, Paola C; Sadayappan, Sakthivel; Hudmon, Andy; Muthuchamy, Mariappan; Powers, Patricia A; Valdivia, Héctor H; Moss, Richard L 2015. Phosphoregulation of Cardiac Inotropy via Myosin Binding Protein-C During Increased Pacing Frequency or ?1-Adrenergic Stimulation. Circulation. Heart failure, 8 3, 595-604

Barefield, David; Kumar, Mohit; de Tombe, Pieter P; Sadayappan, Sakthivel 2014. Contractile dysfunction in a mouse model expressing a heterozygous MYBPC3 mutation associated with hypertrophic cardiomyopathy. American journal of physiology. Heart and circulatory physiology, 306 6, H807-15

Gao, Xianlong; Lin, Brian; Sadayappan, Sakthivel; Patel, Tarun B 2014. Interactions between the regulatory subunit of type I protein kinase A and p90 ribosomal S6 kinase1 regulate cardiomyocyte apoptosis. Molecular pharmacology, 85 2, 357-67

Haynes, Premi; Nava, Kristofer E; Lawson, Benjamin A; Chung, Charles S; Mitov, Mihail I; Campbell, Stuart G; Stromberg, Arnold J; Sadayappan, Sakthivel; Bonnell, Mark R; Hoopes, Charles W; Campbell, Kenneth S 2014. Transmural heterogeneity of cellular level power output is reduced in human heart failure. Journal of molecular and cellular cardiology, 72 , 1-8

Helms, Adam S; Davis, Frank M; Coleman, David; Bartolone, Sarah N; Glazier, Amelia A; Pagani, Francis; Yob, Jaime M; Sadayappan, Sakthivel; Pedersen, Ellen; Lyons, Robert; Westfall, Margaret V; Jones, Richard; Russell, Mark W; Day, Sharlene M 2014. Sarcomere mutation-specific expression patterns in human hypertrophic cardiomyopathy. Circulation. Cardiovascular genetics, 7 4, 434-43

Hoffmann, Jedrzej; Ospelt, Manuel; Troidl, Christian; Voss, Sandra; Liebetrau, Christoph; Kim, Won-Keun; Rolf, Andreas; Wietelmann, Astrid; Braun, Thomas; Troidl, Kerstin; Sadayappan, Sakthivel; Barefield, David; Hamm, Christian; Nef, Holger; Möllmann, Helge 2014. Sham surgery and inter-individual heterogeneity are major determinants of monocyte subset kinetics in a mouse model of myocardial infarction. PloS one, 9 6, e98456

Kuster, Diederik W D; Cardenas-Ospina, Adriana; Miller, Lawson; Liebetrau, Christoph; Troidl, Christian; Nef, Holger M; Möllmann, Helge; Hamm, Christian W; Pieper, Karen S; Mahaffey, Kenneth W; Kleiman, Neal S; Stuyvers, Bruno D; Marian, Ali J; Sadayappan, Sakthivel 2014. Release kinetics of circulating cardiac myosin binding protein-C following cardiac injury. American journal of physiology. Heart and circulatory physiology, 306 4, H547-56

Kuster, Diederik W D; Sadayappan, Sakthivel 2014. MYBPC3's alternate ending: consequences and therapeutic implications of a highly prevalent 25 bp deletion mutation. Pflugers Archiv : European journal of physiology, 466 2, 207-13

Lynch, Thomas L; Sadayappan, Sakthivel 2014. Surviving the infarct: A profile of cardiac myosin binding protein-C pathogenicity, diagnostic utility, and proteomics in the ischemic myocardium. Proteomics. Clinical applications, 8 7-8, 569-77

Sadayappan, Sakthivel; de Tombe, Pieter P 2014. Cardiac myosin binding protein-C as a central target of cardiac sarcomere signaling: a special mini review series. Pflugers Archiv : European journal of physiology, 466 2, 195-200

Simon, Jillian N; Chowdhury, Shamim A K; Warren, Chad M; Sadayappan, Sakthivel; Wieczorek, David F; Solaro, R John; Wolska, Beata M 2014. Ceramide-mediated depression in cardiomyocyte contractility through PKC activation and modulation of myofilament protein phosphorylation. Basic research in cardiology, 109 6, 445

Wang, Li; Ji, Xiang; Barefield, David; Sadayappan, Sakthivel; Kawai, Masakata 2014. Phosphorylation of cMyBP-C affects contractile mechanisms in a site-specific manner. Biophysical journal, 106 5, 1112-22

Wang, Li; Sadayappan, Sakthivel; Kawai, Masakata 2014. Cardiac myosin binding protein C phosphorylation affects cross-bridge cycle's elementary steps in a site-specific manner. PloS one, 9 11, e113417

Wilson, Kristin; Guggilam, Anuradha; West, T Aaron; Zhang, Xiaojin; Trask, Aaron J; Cismowski, Mary J; de Tombe, Pieter; Sadayappan, Sakthivel; Lucchesi, Pamela A 2014. Effects of a myofilament calcium sensitizer on left ventricular systolic and diastolic function in rats with volume overload heart failure. American journal of physiology. Heart and circulatory physiology, 307 11, H1605-17

Witayavanitkul, Namthip; Ait Mou, Younss; Kuster, Diederik W D; Khairallah, Ramzi J; Sarkey, Jason; Govindan, Suresh; Chen, Xin; Ge, Ying; Rajan, Sudarsan; Wieczorek, David F; Irving, Thomas; Westfall, Margaret V; de Tombe, Pieter P; Sadayappan, Sakthivel 2014. Myocardial infarction-induced N-terminal fragment of cardiac myosin-binding protein C (cMyBP-C) impairs myofilament function in human myocardium. The Journal of biological chemistry, 289 13, 8818-27

Govindan, Suresh; Kuster, Diederik Wd; Lin, Brian; Kahn, Daniel J; Jeske, Walter P; Walenga, Jeanine M; Leya, Fred; Hoppensteadt, Debra; Fareed, Jawed; Sadayappan, Sakthivel 2013. Increase in cardiac myosin binding protein-C plasma levels is a sensitive and cardiac-specific biomarker of myocardial infarction. American journal of cardiovascular disease, 3 2, 60-70

Khairallah, Ramzi J; Sadayappan, Sakthivel 2013. Finding the missing link: disulfide-containing proteins via a high-throughput proteomics approach. Proteomics, 13 22, 3245-6

Kuster, Diederik W D; Barefield, David; Govindan, Suresh; Sadayappan, Sakthivel 2013. A sensitive and specific quantitation method for determination of serum cardiac myosin binding protein-C by electrochemiluminescence immunoassay. Journal of visualized experiments : JoVE, 78,

Kuster, Diederik W D; Sequeira, Vasco; Najafi, Aref; Boontje, Nicky M; Wijnker, Paul J M; Witjas-Paalberends, E Rosalie; Marston, Steven B; Dos Remedios, Cristobal G; Carrier, Lucie; Demmers, Jeroen A A; Redwood, Charles; Sadayappan, Sakthivel; van der Velden, Jolanda 2013. GSK3? phosphorylates newly identified site in the proline-alanine-rich region of cardiac myosin-binding protein C and alters cross-bridge cycling kinetics in human: short communication. Circulation research, 112 4, 633-9

Lin, Brian; Govindan, Suresh; Lee, Kyounghwan; Zhao, Piming; Han, Renzhi; Runte, K Elisabeth; Craig, Roger; Palmer, Bradley M; Sadayappan, Sakthivel 2013. Cardiac myosin binding protein-C plays no regulatory role in skeletal muscle structure and function. PloS one, 8 7, e69671

Govindan, Suresh; McElligott, Andrew; Muthusamy, Saminathan; Nair, Nandini; Barefield, David; Martin, Jody L; Gongora, Enrique; Greis, Kenneth D; Luther, Pradeep K; Winegrad, Saul; Henderson, Kyle K; Sadayappan, Sakthivel 2012. Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction. Journal of molecular and cellular cardiology, 52 1, 154-64

Govindan, Suresh; Sarkey, Jason; Ji, Xiang; Sundaresan, Nagalingam R; Gupta, Mahesh P; de Tombe, Pieter P; Sadayappan, Sakthivel 2012. Pathogenic properties of the N-terminal region of cardiac myosin binding protein-C in vitro. Journal of muscle research and cell motility, 33 1, 17-30

Hinken, Aaron C; Hanft, Laurin M; Scruggs, Sarah B; Sadayappan, Sakthivel; Robbins, Jeffery; Solaro, R John; McDonald, Kerry S 2012. Protein kinase C depresses cardiac myocyte power output and attenuates myofilament responses induced by protein kinase A. Journal of muscle research and cell motility, 33 6, 439-48

Howarth, Jack W; Ramisetti, Srinivas; Nolan, Kristof; Sadayappan, Sakthivel; Rosevear, Paul R 2012. Structural insight into unique cardiac myosin-binding protein-C motif: a partially folded domain. The Journal of biological chemistry, 287 11, 8254-62

Sadayappan, Sakthivel; de Tombe, Pieter P 2012. Cardiac myosin binding protein-C: redefining its structure and function. Biophysical reviews, 4 2, 93-106

Verma, Suresh Kumar; Krishnamurthy, Prasanna; Barefield, David; Singh, Neha; Gupta, Rajesh; Lambers, Erin; Thal, Melissa; Mackie, Alexander; Hoxha, Eneda; Ramirez, Veronica; Qin, Gangjian; Sadayappan, Sakthivel; Ghosh, Asish K; Kishore, Raj 2012. Interleukin-10 treatment attenuates pressure overload-induced hypertrophic remodeling and improves heart function via signal transducers and activators of transcription 3-dependent inhibition of nuclear factor-?B. Circulation, 126 4, 418-29

Sadayappan, Sakthivel; Gulick, James; Osinska, Hanna; Barefield, David; Cuello, Friederike; Avkiran, Metin; Lasko, Valerie M; Lorenz, John N; Maillet, Marjorie; Martin, Jody L; Brown, Joan Heller; Bers, Donald M; Molkentin, Jeffery D; James, Jeanne; Robbins, Jeffrey 2011. A critical function for Ser-282 in cardiac Myosin binding protein-C phosphorylation and cardiac function. Circulation research, 109 2, 141-50

Barefield, David; Sadayappan, Sakthivel 2010. Phosphorylation and function of cardiac myosin binding protein-C in health and disease. Journal of molecular and cellular cardiology, 48 5, 866-75

Nicolaou, Persoulla; Rodriguez, Patricia; Ren, Xiaoping; Zhou, Xiaoyang; Qian, Jiang; Sadayappan, Sakthivel; Mitton, Bryan; Pathak, Anand; Robbins, Jeffrey; Hajjar, Roger J; Jones, Keith; Kranias, Evangelia G 2009. Inducible expression of active protein phosphatase-1 inhibitor-1 enhances basal cardiac function and protects against ischemia/reperfusion injury. Circulation research, 104 8, 1012-20

Sadayappan, Sakthivel; Gulick, James; Klevitsky, Raisa; Lorenz, John N; Sargent, Michelle; Molkentin, Jeffery D; Robbins, Jeffrey 2009. Cardiac myosin binding protein-C phosphorylation in a {beta}-myosin heavy chain background. Circulation, 119 9, 1253-62

Sadayappan, Sakthivel; Finley, Natosha; Howarth, Jack W; Osinska, Hanna; Klevitsky, Raisa; Lorenz, John N; Rosevear, Paul R; Robbins, Jeffrey 2008. Role of the acidic N' region of cardiac troponin I in regulating myocardial function. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 22 4, 1246-57

Sadayappan, Sakthivel; Robbins, Jeffrey 2008. The death of transcriptional chauvinism in the control and regulation of cardiac contractility. Annals of the New York Academy of Sciences, 1123 , 1-9

Krenz, Maike; Sadayappan, Sakthivel; Osinska, Hanna E; Henry, Jeffrey A; Beck, Samantha; Warshaw, David M; Robbins, Jeffrey 2007. Distribution and structure-function relationship of myosin heavy chain isoforms in the adult mouse heart. The Journal of biological chemistry, 282 33, 24057-64

Sadayappan, Sakthivel; Osinska, Hanna; Klevitsky, Raisa; Lorenz, John N; Sargent, Michelle; Molkentin, Jeffrey D; Seidman, Christine E; Seidman, Jonathan G; Robbins, Jeffrey 2006. Cardiac myosin binding protein C phosphorylation is cardioprotective. Proceedings of the National Academy of Sciences of the United States of America, 103 45, 16918-23

Sadayappan, Sakthivel; Gulick, James; Osinska, Hanna; Martin, Lisa A; Hahn, Harvey S; Dorn, Gerald W; Klevitsky, Raisa; Seidman, Christine E; Seidman, Jonathan G; Robbins, Jeffrey 2005. Cardiac myosin-binding protein-C phosphorylation and cardiac function. Circulation research, 97 11, 1156-63