Skip to main content
Photo of  Sakthivel Sadayappan, Ph.D., M.B.A.

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

Professor

Vice Chair of Basic Research, Internal Medicine; Director of Heart Branch of the UC Heart, Lung and Vascular Institute; Division of Cardiovascular Health and Disease;

Internal Medicine | College of Medicine

Education/Credentials
  • MBA: University of Cincinnati
  • PhD: Madurai Kamaraj University
Contact Information
Research 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. 

Summary

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. The sarcomere is the functional unit of striated muscle to generate contractility. Accordingly, the Sadayappan Lab has consistently focused on improving cardiac sarcomere function during ischemia-reperfusion injury. We have learned that sarcomere proteins undergo severe proteolytic damage during ischemia-reperfusion injury, resulting decreased contractile force and cardiac function. Therefore, the short-term goals of current research studies involve 1) identifying cardiac-specific early biomarkers of HF (NIH-NHLBI K02HL114749), 2) restoring sarcomere structure and function (NIH-NHLBI R01HL105826), and 3) screening for compounds to improve sarcomere function during ischemia-reperfusion injury. In particular, hypertrophic cardiomyopathy (HCM) is a major genetic disorder among populations of South Asian descent, leading to contractile dysfunction, heart failure, and sudden cardiac death. Therefore, we are also engaged in determining the pathophysiological mechanism of the South Asian-specific MYBPC3 gene variant that has been associated with the development of HCM. Using various mouse models and in vitro culture systems expressing the MYBPC3 gene variant, we aim to unravel the molecular mechanisms associated this mutant (NIH-NHLBI R01HL130356). To carry out this study, we are performing genome-phenome analysis in South Asians who carry the MYBPC3 gene variant and who live in the USA (AHA 15CVGPSD27020012). Finally, in an unrelated, but nonetheless pivotal, study, we are studying the differential role(s) of slow and fast myosin binding protein-C in skeletal muscles (R01AR067279, PI: Craig and Warshaw), using both in vitro culture systems and animal models. As part of our commitment to the development of young scientists, the Sadayappan Lab provides expertise and training in cell biology, molecular biology, structural biology and physiology of the muscle and encourages collaborations in various areas of muscle biology. 

Peer Reviewed Publications

Becker, Richard C; Owens, A Phillip; Sadayappan, Sakthivel 2020. Tissue-level inflammation and ventricular remodeling in hypertrophic cardiomyopathy. Journal of thrombosis and thrombolysis, 49 2, 177-183

Becker, Richard C; Sadayappan, Sakthivel 2020. Designing Human In Vitro Models for Drug Development. Journal of the American College of Cardiology, 75 6, 587-589

Butts, Brittany; Ahmed, Mustafa I; Bajaj, Navkaranbir S; Cox Powell, Pamela; Pat, Betty; Litovsky, Silvio; Gupta, Himanshu; Lloyd, Steven G; Denney, Thomas S; Zhang, Xiaoxia; Aban, Inmaculada; Sadayappan, Sakthivel; McNamara, James W; Watson, Michael J; Ferrario, Carlos M; Collawn, James F; Lewis, Clifton; Davies, James E; Dell'Italia, Louis J 2020. Reduced Left Atrial Emptying Fraction and Chymase Activation in Pathophysiology of Primary Mitral Regurgitation. JACC. Basic to translational science, 5 2, 109-122

Vagnozzi, Ronald J; Maillet, Marjorie; Sargent, Michelle A; Khalil, Hadi; Johansen, Anne Katrine Z; Schwanekamp, Jennifer A; York, Allen J; Huang, Vincent; Nahrendorf, Matthias; Sadayappan, Sakthivel; Molkentin, Jeffery D 2020. An acute immune response underlies the benefit of cardiac stem cell therapy. Nature, 577 7790, 405-409

Alam, Perwez; Haile, Bereket; Arif, Mohammed; Pandey, Raghav; Rokvic, Miso; Nieman, Michelle; Maliken, Bryan D; Paul, Arghya; Wang, Yi-Gang; Sadayappan, Sakthivel; Ahmed, Rafeeq P H; Kanisicak, Onur 2019. Inhibition of Senescence-Associated Genes Rb1 and Meis2 in Adult Cardiomyocytes Results in Cell Cycle Reentry and Cardiac Repair Post-Myocardial Infarction. Journal of the American Heart Association, 8 15, e012089

Arif, Mohammed; Sadayappan, Sakthivel; Becker, Richard C; Martin, Lisa J; Urbina, Elaine M 2019. Epigenetic modification: a regulatory mechanism in essential hypertension. Hypertension research : official journal of the Japanese Society of Hypertension, 42 8, 1099-1113

Barefield, David Y; McNamara, James W; Lynch, Thomas L; Kuster, Diederik W D; Govindan, Suresh; Haar, Lauren; Wang, Yang; Taylor, Erik N; Lorenz, John N; Nieman, Michelle L; Zhu, Guangshuo; Luther, Pradeep K; Varró, Andras; Dobrev, Dobromir; Ai, Xun; Janssen, Paul M L; Kass, David A; Jones, Walter Keith; Gilbert, Richard J; Sadayappan, Sakthivel 2019. Ablation of the calpain-targeted site in cardiac myosin binding protein-C is cardioprotective during ischemia-reperfusion injury. Journal of molecular and cellular cardiology, 129 , 236-246

Becker, Richard C; Cotarlan, Vlad; Sadayappan, Sakthi 2019. The rapid proliferation of solicited content online journals: a quest to disseminate knowledge? Journal of thrombosis and thrombolysis, 47 3, 337-344

Boyer, Justin G; Prasad, Vikram; Song, Taejeong; Lee, Donghoon; Fu, Xing; Grimes, Kelly M; Sargent, Michelle A; Sadayappan, Sakthivel; Molkentin, Jeffery D 2019. ERK1/2 signaling induces skeletal muscle slow fiber-type switching and reduces muscular dystrophy disease severity. JCI insight, 5 ,

Goh, Qingnian; Song, Taejeong; Petrany, Michael J; Cramer, Alyssa Aw; Sun, Chengyi; Sadayappan, Sakthivel; Lee, Se-Jin; Millay, Douglas P 2019. Myonuclear accretion is a determinant of exercise-induced remodeling in skeletal muscle. eLife, 8 ,

Ikeda, Shohei; Mizushima, Wataru; Sciarretta, Sebastiano; Abdellatif, Maha; Zhai, Peiyong; Mukai, Risa; Fefelova, Nadezhda; Oka, Shin-Ichi; Nakamura, Michinari; Del Re, Dominic P; Farrance, Iain; Park, Ji Yeon; Tian, Bin; Xie, Lai-Hua; Kumar, Mohit; Hsu, Chiao-Po; Sadayappan, Sakthivel; Shimokawa, Hiroaki; Lim, Dae-Sik; Sadoshima, Junichi 2019. Hippo Deficiency Leads to Cardiac Dysfunction Accompanied by Cardiomyocyte Dedifferentiation During Pressure Overload. Circulation research, 124 2, 292-305

Kuster, Diederik W D; Lynch, Thomas L; Barefield, David Y; Sivaguru, Mayandi; Kuffel, Gina; Zilliox, Michael J; Lee, Kyoung Hwan; Craig, Roger; Namakkal-Soorappan, Rajasekaran; Sadayappan, Sakthivel 2019. Altered C10 domain in cardiac myosin binding protein-C results in hypertrophic cardiomyopathy. Cardiovascular research, 115 14, 1986-1997

Li, Amy; Nelson, Shane R; Rahmanseresht, Sheema; Braet, Filip; Cornachione, Anabelle S; Previs, Samantha Beck; O'Leary, Thomas S; McNamara, James W; Rassier, Dilson E; Sadayappan, Sakthivel; Previs, Michael J; Warshaw, David M 2019. Skeletal MyBP-C isoforms tune the molecular contractility of divergent skeletal muscle systems. Proceedings of the National Academy of Sciences of the United States of America, 116 43, 21882-21892

Manoharan, Palanikumar; Song, Taejeong; Radzyukevich, Tatiana L; Sadayappan, Sakthivel; Lingrel, Jerry B; Heiny, Judith A 2019. KLF2 in Myeloid Lineage Cells Regulates the Innate Immune Response during Skeletal Muscle Injury and Regeneration. iScience, 17 , 334-346

McNamara, James W; Singh, Rohit R; Sadayappan, Sakthivel 2019. Cardiac myosin binding protein-C phosphorylation regulates the super-relaxed state of myosin. Proceedings of the National Academy of Sciences of the United States of America, 116 24, 11731-11736

O'Leary, Thomas S; Snyder, Julia; Sadayappan, Sakthivel; Day, Sharlene M; Previs, Michael J 2019. MYBPC3 truncation mutations enhance actomyosin contractile mechanics in human hypertrophic cardiomyopathy. Journal of molecular and cellular cardiology, 127 , 165-173

Sadayappan, Sakthivel 2019. Cardiovascular Leaders Are Made, not Born. Circulation research, 124 4, 484-487

Sadayappan, Sakthivel; Gilbert, Richard J 2019. The potential role of neddylation in pre- and postnatal cardiac remodeling. American journal of physiology. Heart and circulatory physiology, 317 2, H276-H278

Song, Taejeong; Manoharan, Palanikumar; Millay, Douglas P; Koch, Sheryl E; Rubinstein, Jack; Heiny, Judith A; Sadayappan, Sakthivel 2019. Dilated cardiomyopathy-mediated heart failure induces a unique skeletal muscle myopathy with inflammation. Skeletal muscle, 9 1, 4

Song, Taejeong; Sadayappan, Sakthivel 2019. Featured characteristics and pivotal roles of satellite cells in skeletal muscle regeneration. Journal of muscle research and cell motility, ,

Tabish, Ali M; Arif, Mohammed; Song, Taejeong; Elbeck, Zaher; Becker, Richard C; Knöll, Ralph; Sadayappan, Sakthivel 2019. Association of intronic DNA methylation and hydroxymethylation alterations in the epigenetic etiology of dilated cardiomyopathy. American journal of physiology. Heart and circulatory physiology, 317 1, H168-H180

Toepfer, Christopher N; Wakimoto, Hiroko; Garfinkel, Amanda C; McDonough, Barbara; Liao, Dan; Jiang, Jianming; Tai, Angela C; Gorham, Joshua M; Lunde, Ida G; Lun, Mingyue; Lynch, Thomas L; McNamara, James W; Sadayappan, Sakthivel; Redwood, Charles S; Watkins, Hugh C; Seidman, Jonathan G; Seidman, Christine E 2019. Hypertrophic cardiomyopathy mutations in MYBPC3 dysregulate myosin. Science translational medicine, 11 476,

Vagnozzi, Ronald J; Pfleger, Jessica; Sadayappan, Sakthivel 2019. Basic Cardiovascular Sciences Scientific Sessions 2019: Integrative Approaches to Complex Cardiovascular Diseases. Circulation research, 125 10, 924-931

Hoffman, Matthew P; Taylor, Erik N; Aninwene, George E; Sadayappan, Sakthivel; Gilbert, Richard J 2018. Assessing the multiscale architecture of muscular tissue with Q-space magnetic resonance imaging: Review. Microscopy research and technique, 81 2, 162-170

Huang, Wei; Feng, Yuliang; Liang, Jialiang; Yu, Hao; Wang, Cheng; Wang, Boyu; Wang, Mingyang; Jiang, Lin; Meng, Wei; Cai, Wenfeng; Medvedovic, Mario; Chen, Jenny; Paul, Christian; Davidson, W Sean; Sadayappan, Sakthivel; Stambrook, Peter J; Yu, Xi-Yong; Wang, Yigang 2018. Loss of microRNA-128 promotes cardiomyocyte proliferation and heart regeneration. Nature communications, 9 1, 700

Lin, Brian Leei; Li, Amy; Mun, Ji Young; Previs, Michael J; Previs, Samantha Beck; Campbell, Stuart G; Dos Remedios, Cristobal G; Tombe, Pieter de P; Craig, Roger; Warshaw, David M; Sadayappan, Sakthivel 2018. Skeletal myosin binding protein-C isoforms regulate thin filament activity in a Ca2+-dependent manner. Scientific reports, 8 1, 2604

McNamara, James W; Grimes, Kelly M; Sadayappan, Sakthivel 2018. Basic Cardiovascular Sciences Scientific Sessions 2018. Circulation research, 123 9, 1024-1029

McNamara, James W; Sadayappan, Sakthivel 2018. Skeletal myosin binding protein-C: An increasingly important regulator of striated muscle physiology. Archives of biochemistry and biophysics, 660 , 121-128

Robbins, Nathan; Gilbert, Mark; Kumar, Mohit; McNamara, James W; Daly, Patrick; Koch, Sheryl E; Conway, Ginger; Effat, Mohamed; Woo, Jessica G; Sadayappan, Sakthivel; Rubinstein, Jack 2018. Probenecid Improves Cardiac Function in Patients With Heart Failure With Reduced Ejection Fraction In Vivo and Cardiomyocyte Calcium Sensitivity In Vitro. Journal of the American Heart Association, 7 2,

Sadayappan, Sakthivel 2018. My Life, My Heart, and My(osin) Binding Protein-C. Circulation research, 122 7, 918-920

Smyrnias, Ioannis; Goodwin, Normann; Wachten, Dagmar; Skogestad, Jonas; Aronsen, Jan Magnus; Robinson, Emma L; Demydenko, Kateryna; Segonds-Pichon, Anne; Oxley, David; Sadayappan, Sakthivel; Sipido, Karin; Bootman, Martin D; Roderick, H Llewelyn 2018. Contractile responses to endothelin-1 are regulated by PKC phosphorylation of cardiac myosin binding protein-C in rat ventricular myocytes. Journal of molecular and cellular cardiology, 117 , 1-18

Viswanathan, Shiv Kumar; Puckelwartz, Megan J; Mehta, Ashish; Ramachandra, Chrishan J A; Jagadeesan, Aravindakshan; Fritsche-Danielson, Regina; Bhat, Ratan V; Wong, Philip; Kandoi, Sangeetha; Schwanekamp, Jennifer A; Kuffel, Gina; Pesce, Lorenzo L; Zilliox, Michael J; Durai, U Nalla B; Verma, Rama Shanker; Molokie, Robert E; Suresh, Domodhar P; Khoury, Philip R; Thomas, Annie; Sanagala, Thriveni; Tang, Hak Chiaw; Becker, Richard C; Knöll, Ralph; Shim, Winston; McNally, Elizabeth M; Sadayappan, Sakthivel 2018. Association of Cardiomyopathy With MYBPC3 D389V and MYBPC3?25bpIntronic Deletion in South Asian Descendants. JAMA cardiology, 3 6, 481-488

Arif, Mohammed; Pandey, Raghav; Alam, Perwez; Jiang, Shujia; Sadayappan, Sakthivel; Paul, Arghya; Ahmed, Rafeeq P H 2017. MicroRNA-210-mediated proliferation, survival, and angiogenesis promote cardiac repair post myocardial infarction in rodents. Journal of molecular medicine (Berlin, Germany), 95 12, 1369-1385

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, 469 12, 1603-1613

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

Lynch, Thomas L; Ismahil, Mohamed Ameen; Jegga, Anil G; Zilliox, Michael J; Troidl, Christian; Prabhu, Sumanth D; Sadayappan, Sakthivel 2017. Cardiac inflammation in genetic dilated cardiomyopathy caused by MYBPC3 mutation. Journal of molecular and cellular cardiology, 102 , 83-93

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

Sadayappan, Sakthivel 2017. The Myofilament Field Revisited in the Age of Cellular and Molecular Biology. Circulation research, 121 6, 601-603

Sadayappan, Sakthivel 2017. Cardiovascular Early Careers: Past and Present. Circulation research, 121 2, 100-102

Sivaguru, Mayandi; Kabir, Mohammad M; Gartia, Manas Ranjan; Biggs, David S C; Sivaguru, Barghav S; Sivaguru, Vignesh A; Fried, Glenn A; Liu, Gang Logan; Sadayappan, Sakthivel; Toussaint, Kimani C 2017. Application of an advanced maximum likelihood estimation restoration method for enhanced-resolution and contrast in second-harmonic generation microscopy. Journal of microscopy, 267 3, 397-408

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

Viswanathan, Shiv Kumar; Sanders, Heather K; McNamara, James W; Jagadeesan, Aravindakshan; Jahangir, Arshad; Tajik, A Jamil; Sadayappan, Sakthivel 2017. Hypertrophic cardiomyopathy clinical phenotype is independent of gene mutation and mutation dosage. PloS one, 12 11, e0187948

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,

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

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

Sivaguru, Mayandi; Fried, Glenn; Sivaguru, Barghav S; Sivaguru, Vignesh A; Lu, Xiaochen; Choi, Kyung Hwa; Saif, M Taher A; Lin, Brian; Sadayappan, Sakthivel 2015. Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy. BioTechniques, 59 5, 295-308

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

Guggilam, Anuradha; Hutchinson, Kirk R; West, T Aaron; Kelly, Amy P; Galantowicz, Maarten L; Davidoff, Amy J; Sadayappan, Sakthivel; Lucchesi, Pamela A 2013. In vivo and in vitro cardiac responses to beta-adrenergic stimulation in volume-overload heart failure. Journal of molecular and cellular cardiology, 57 , 47-58

Guillory, Ashley N; Yin, Xing; Wijaya, Cori S; Diaz Diaz, Andrea C; Rababa'h, Abeer; Singh, Sonal; Atrooz, Fatin; Sadayappan, Sakthivel; McConnell, Bradley K 2013. Enhanced cardiac function in Gravin mutant mice involves alterations in the ?-adrenergic receptor signaling cascade. PloS one, 8 9, e74784

Hwang, Hyosook; Robinson, Dustin; Rogers, Julie B; Stevenson, Tamara K; Lang, Sarah E; Sadayappan, Sakthivel; Day, Sharlene M; Sivaramakrishnan, Sivaraj; Westfall, Margaret V 2013. Agonist activated PKC?II translocation and modulation of cardiac myocyte contractile function. Scientific reports, 3 , 1971

Jin, Chun Zi; Jang, Ji Hyun; Kim, Hae Jin; Wang, Yue; Hwang, In-Chang; Sadayappan, Sakthivel; Park, Byung Mun; Kim, Suhn Hee; Jin, Zhe Hu; Seo, Eun Yeong; Kim, Kyung-Hee; Kim, Yong-Jin; Kim, Sung Joon; Zhang, Yin Hua 2013. Myofilament Ca2+ desensitization mediates positive lusitropic effect of neuronal nitric oxide synthase in left ventricular myocytes from murine hypertensive heart. Journal of molecular and cellular cardiology, 60 , 107-15

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

Sequeira, Vasco; Wijnker, Paul J M; Nijenkamp, Louise L A M; Kuster, Diederik W D; Najafi, Aref; Witjas-Paalberends, E Rosalie; Regan, Jessica A; Boontje, Nicky; Ten Cate, Folkert J; Germans, Tjeerd; Carrier, Lucie; Sadayappan, Sakthivel; van Slegtenhorst, Marjon A; Zaremba, Ruud; Foster, D Brian; Murphy, Anne M; Poggesi, Corrado; Dos Remedios, Cris; Stienen, Ger J M; Ho, Carolyn Y; Michels, Michelle; van der Velden, Jolanda 2013. Perturbed length-dependent activation in human hypertrophic cardiomyopathy with missense sarcomeric gene mutations. Circulation research, 112 11, 1491-505

Dirkx, Ellen; Cazorla, Olivier; Schwenk, Robert W; Lorenzen-Schmidt, Ilka; Sadayappan, Sakthivel; Van Lint, Johan; Carrier, Lucie; van Eys, Guillaume J J M; Glatz, Jan F C; Luiken, Joost J F P 2012. Protein kinase D increases maximal Ca2+-activated tension of cardiomyocyte contraction by phosphorylation of cMyBP-C-Ser315. American journal of physiology. Heart and circulatory physiology, 303 3, H323-31

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

Hwang, Hyosook; Robinson, Dustin A; Stevenson, Tamara K; Wu, Helen C; Kampert, Sarah E; Pagani, Francis D; Dyke, D Brad; Martin, Jody L; Sadayappan, Sakthival; Day, Sharlene M; Westfall, Margaret V 2012. PKC?II modulation of myocyte contractile performance. Journal of molecular and cellular cardiology, 53 2, 176-86

Sadayappan, Sakthivel 2012. Cardiac myosin binding protein-C: a potential early-stage, cardiac-specific biomarker of ischemia-reperfusion injury. Biomarkers in medicine, 6 1, 69-72

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

van Dijk, Sabine J; Paalberends, E Rosalie; Najafi, Aref; Michels, Michelle; Sadayappan, Sakthivel; Carrier, Lucie; Boontje, Nicky M; Kuster, Diederik W D; van Slegtenhorst, Marjon; Dooijes, Dennis; dos Remedios, Cris; ten Cate, Folkert J; Stienen, Ger J M; van der Velden, Jolanda 2012. Contractile dysfunction irrespective of the mutant protein in human hypertrophic cardiomyopathy with normal systolic function. Circulation. Heart failure, 5 1, 36-46

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

Weith, Abbey; Sadayappan, Sakthivel; Gulick, James; Previs, Michael J; Vanburen, Peter; Robbins, Jeffrey; Warshaw, David M 2012. 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. Journal of molecular and cellular cardiology, 52 1, 219-27

Cuello, Friederike; Bardswell, Sonya C; Haworth, Robert S; Ehler, Elisabeth; Sadayappan, Sakthivel; Kentish, Jonathan C; Avkiran, Metin 2011. Novel role for p90 ribosomal S6 kinase in the regulation of cardiac myofilament phosphorylation. The Journal of biological chemistry, 286 7, 5300-10

Palmer, Bradley M; Sadayappan, Sakthivel; Wang, Yuan; Weith, Abbey E; Previs, Michael J; Bekyarova, Tanya; Irving, Thomas C; Robbins, Jeffrey; Maughan, David W 2011. Roles for cardiac MyBP-C in maintaining myofilament lattice rigidity and prolonging myosin cross-bridge lifetime. Biophysical journal, 101 7, 1661-9

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

Bardswell, Sonya C; Cuello, Friederike; Rowland, Alexandra J; Sadayappan, Sakthivel; Robbins, Jeffrey; Gautel, Mathias; Walker, Jeffery W; Kentish, Jonathan C; Avkiran, Metin 2010. Distinct sarcomeric substrates are responsible for protein kinase D-mediated regulation of cardiac myofilament Ca2+ sensitivity and cross-bridge cycling. The Journal of biological chemistry, 285 8, 5674-82

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

Copeland, O'Neal; Sadayappan, Sakthivel; Messer, Andrew E; Steinen, Ger J M; van der Velden, Jolanda; Marston, Steven B 2010. Analysis of cardiac myosin binding protein-C phosphorylation in human heart muscle. Journal of molecular and cellular cardiology, 49 6, 1003-11

Senapathy, Periannan; Bhasi, Ashwini; Mattox, Jeffrey; Dhandapany, Perundurai S; Sadayappan, Sakthivel 2010. Targeted genome-wide enrichment of functional regions. PloS one, 5 6, e11138

Dhandapany, Perundurai S; Sadayappan, Sakthivel; Xue, Yali; Powell, Gareth T; Rani, Deepa Selvi; Nallari, Prathiba; Rai, Taranjit Singh; Khullar, Madhu; Soares, Pedro; Bahl, Ajay; Tharkan, Jagan Mohan; Vaideeswar, Pradeep; Rathinavel, Andiappan; Narasimhan, Calambur; Ayapati, Dharma Rakshak; Ayub, Qasim; Mehdi, S Qasim; Oppenheimer, Stephen; Richards, Martin B; Price, Alkes L; Patterson, Nick; Reich, David; Singh, Lalji; Tyler-Smith, Chris; Thangaraj, Kumarasamy 2009. A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia. Nature genetics, 41 2, 187-91

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

Dhandapany, Perundurai S; Sadayappan, Sakthivel; Vanniarajan, Ayyasamy; Karthikeyan, Bose; Nagaraj, Chandran; Gowrishankar, Kalpana; Selvam, Govindan Sadasivam; Singh, Lalji; Thangaraj, Kumarasamy 2007. Novel mitochondrial DNA mutations implicated in Noonan syndrome. International journal of cardiology, 120 2, 284-5

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

Nagayama, Takahiro; Takimoto, Eiki; Sadayappan, Sakthivel; Mudd, James O; Seidman, J G; Robbins, Jeffrey; Kass, David A 2007. Control of in vivo left ventricular [correction] contraction/relaxation kinetics by myosin binding protein C: protein kinase A phosphorylation dependent and independent regulation. Circulation, 116 21, 2399-408

Yasuda, So-ichiro; Coutu, Pierre; Sadayappan, Sakthivel; Robbins, Jeffrey; Metzger, Joseph M 2007. Cardiac transgenic and gene transfer strategies converge to support an important role for troponin I in regulating relaxation in cardiac myocytes. Circulation research, 101 4, 377-86

Annapoorani, Ponnambalam; Dhandapany, Perundurai S; Sadayappan, Sakthivel; Ramasamy, Subbiah; Rathinavel, Andiappan; Selvam, Govindan Sadasivam 2006. Cardiac isoform of alpha-2 macroglobulin--a new biomarker for myocardial infarcted diabetic patients. Atherosclerosis, 186 1, 173-6

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

Wang, Hao; Grant, Jennifer E; Doede, Christopher M; Sadayappan, Sakthivel; Robbins, Jeffrey; Walker, Jeffery W 2006. PKC-betaII sensitizes cardiac myofilaments to Ca2+ by phosphorylating troponin I on threonine-144. Journal of molecular and cellular cardiology, 41 5, 823-33

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