Publications

Barefield DY, Lynch TL 4th, Jagadeesan A, Sanagala T, Sadayappan S.
High-Throughput diagnostic assay for a highly prevalent cardiomyopathy-associated MYBPC3 variant. J Mol Biomark Diagn. 2016 Nov;7(6) PMC5160998.

Lynch TL 4th, Ismahil MA, Jegga AG, Zilliox MJ, Troidl C, Prabhu SD, Sadayappan S.
Cardiac inflammation in genetic dilated cardiomyopathy caused by MYBPC3 mutation. J Mol Cell Cardiol. 2016 Dec 10;102:83-93 PMID: 27955979.

Kraker J, Viswanathan SK, Knöll R, Sadayappan S.
Recent Advances in the Molecular genetics of familial hypertrophic cardiomyopathy in South Asian Descendants. Front Physiol. 2016 Oct 28;7:499 PMC5083855.

Hoffman MP, Taylor EN, Aninwene GE 2nd, Sadayappan S., Gilbert RJ.
Assessing the multiscale architecture of muscular tissue with Q-space magnetic resonance imaging: Review. Microsc Res Tech. 2016 Oct 2. doi: 10.1002/jemt.22777. [Epub ahead of print] PMID: 27696640.

Lipps C, Nguyen JH, Pyttel L, Lynch TL 4th, Liebetrau C, Aleshcheva G, Voss S, Dörr O, Nef HM, Möllmann H, Hamm CW, Sadayappan S., Troidl C.
N-terminal fragment of cardiac myosin binding protein-C triggers pro-inflammatory responses in vitro. J Mol Cell Cardiol. 2016 Oct;99:47-56 PMC5107329.

Taylor EN, Hoffman MP, Barefield DY, Aninwene GE 2nd, Abrishamchi AD, Lynch TL 4th, Govindan S, Osinska H, Robbins J, Sadayappan S., Gilbert RJ.
Alterations in multi-scale cardiac architecture in association with phosphorylation of myosin binding protein-C. J Am Heart Assoc. 2016 Mar 15;5(3):e002836 PMC4943261.

Stathopoulou K, Wittig I, Heidler J, Piasecki A, Richter F, Diering S, van der Velden J, Buck F, Donzelli S, Schröder E, Wijnker PJ, Voigt N, Dobrev D, Sadayappan S., Eschenhagen T, Carrier L, Eaton P, Cuello F. S-glutathiolation impairs phosphoregulation and function of cardiac myosin-binding protein C in human heart failure. FASEB J. 2016 May;30(5):1849-64 PMC4836368.

Sivaguru M, Fried G, Sivaguru BS, Sivaguru VA, Lu X, Choi KH, Saif MT, Lin B, Sadayappan S..
Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy. Biotechniques. 2015 Nov 1;59(5):295-308 PMID: 26554507.

Lynch TL 4th, Sivaguru M, Velayutham M, Cardounel AJ, Michels M, Barefield D, Govindan S, dos Remedios C, van der Velden J, Sadayappan S. Oxidative Stress in Dilated cardiomyopathy caused by MYBPC3 mutation. Oxid Med Cell Longev. 2015;2015:424751 PMC4609873.

Thoonen R, Giovanni S, Govindan S, Lee DI, Wang GR, Calamaras TD, Takimoto E, Kass DA, Sadayappan S, Blanton RM. Molecular Screen Identifies Cardiac Myosin-Binding Protein-C as a Protein Kinase G-Iα Substrate. Circ Heart Fail. 2015 Nov;8(6):1115-22 PMC4651836.

Kumar M, Govindan S, Zhang M, Khairallah RJ, Martin JL, Sadayappan S, de Tombe PP. Cardiac myosin-binding protein C and Troponin-I phosphorylation independently modulate myofilament length-dependent activation. J Biol Chem. 2015 Dec 4;290(49):29241-9 PMC4705930.

Tong CW, Wu X, Liu Y, Rosas PC, Sadayappan S, Hudmon A, Muthuchamy M, Powers PA, Valdivia HH, Moss RL. Phosphoregulation of cardiac inotropy via myosin binding protein-C during increased pacing frequency or β1-adrenergic stimulation. Circ Heart Fail. 2015 May;8(3):595-604 PMC4439328.

Kuster DW, Govindan S, Springer TI, Martin JL, Finley NL, Sadayappan S. A hypertrophic cardiomyopathy-associated MYBPC3 mutation common in populations of South Asian descent causes contractile dysfunction. J Biol Chem. 2015 Feb 27;290(9):5855-67 PMC4342493.

Barefield D, Kumar M, Gorham J, Seidman JG, Seidman CE, de Tombe PP, Sadayappan S. Haploinsufficiency of MYBPC3 exacerbates the development of hypertrophic cardiomyopathy in heterozygous mice. J Mol Cell Cardiol. 2015 Feb;79:234-43 PMC4642280.

Lee K, Harris SP, Sadayappan S, Craig R. Orientation of myosin binding protein C in the cardiac muscle sarcomere determined by domain-specific immuno-EM. J Mol Biol. 2015 Jan 30;427(2):274-86 PMC4297556.

Wang L, Sadayappan S, Kawai M. Cardiac myosin binding protein-C phosphorylation affects cross-bridge cycle's elementary steps in a site-specific manner. PLoS One. 2014 Nov 24;9(11):e113417 PMC4242647.

Simon JN, Chowdhury SA, Warren CM, Sadayappan S, Wieczorek DF, Solaro RJ, Wolska BM. Ceramide-mediated depression in cardiomyocyte contractility through PKC activation and modulation of myofilament protein phosphorylation. Basic Res Cardiol. 2014;109(6):445 PMC4440670.

Wilson K, Guggilam A, West TA, Zhang X, Trask AJ, Cismowski MJ, de Tombe P, Sadayappan S, Lucchesi PA. Effects of a myofilament calcium sensitizer on left ventricular systolic and diastolic function in rats with volume overload heart failure. Am J Physiol Heart Circ Physiol. 2014 Dec 1;307(11):H1605-17 PMC4255015.

Helms AS, Davis FM, Coleman D, Bartolone SN, Glazier AA, Pagani F, Yob JM, Sadayappan S, Pedersen E, Lyons R, Westfall MV, Jones R, Russell MW, Day SM. Sarcomere mutation-specific expression patterns in human hypertrophic cardiomyopathy. Circ Cardiovasc Genet. 2014 Aug;7(4):434-43 PMC4254656.

Hoffmann J, Ospelt M, Troidl C, Voss S, Liebetrau C, Kim WK, Rolf A, Wietelmann A, Braun T, Troidl K, Sadayappan S., Barefield D, Hamm C, Nef H, Möllmann H. Sham surgery and inter-individual heterogeneity are major determinants of monocyte subset kinetics in a mouse model of myocardial infarction. PLoS One. 2014 Jun 3;9(6):e98456 PMC4043649.

Lynch TL, Sadayappan S.. Surviving the infarct: A profile of cardiac myosin binding protein-C pathogenicity, diagnostic utility, and proteomics in the ischemic myocardium. Proteomics Clin Appl. 2014 Aug;8(7-8):569-77 PMC4162529.

Wang L, Ji X, Barefield D, Sadayappan S., Kawai M. Phosphorylation of cMyBP-C affects contractile mechanisms in a site-specific manner. Biophys J. 2014 Mar 4;106(5):1112-22 PMC4026776.

Alves ML, Dias FA, Gaffin RD, Simon JN, Montminy EM, Biesiadecki BJ, Hinken AC, Warren CM, Utter MS, Davis RT 3rd, Sadayappan S., Robbins J, Wieczorek DF, Solaro RJ, Wolska BM. Desensitization of myofilaments to Ca2+ as a therapeutic target for hypertrophic cardiomyopathy with mutations in thin filament proteins. Am J Physiol Heart Circ Physiol. 2014 Apr;7(2):132-43 PMID: 24585742.

Haynes P, Nava KE, Lawson BA, Chung CS, Mitov MI, Campbell SG, Stromberg AJ, Sadayappan S., Bonnell MR, Hoopes CW, Campbell KS. Transmural heterogeneity of cellular level power output is reduced in human heart failure. J Mol Cell Cardiol. 2014 Jul;72:1-8 PMC4037376.

Witayavanitkul N, Ait Mou Y, Kuster DW, Khairallah RJ, Sarkey J, Govindan S, Chen X, Ge Y, Rajan S, Wieczorek DF, Irving T, Westfall MV, de Tombe PP, Sadayappan S.. Myocardial infarction-induced N-terminal fragment of cardiac myosin-binding protein C (cMyBP-C) impairs myofilament function in human myocardium. J Biol Chem. 2014 Mar 28;289(13):8818-27 PMC3979389.

Barefield D, Kumar M, de Tombe PP, Sadayappan S.. Contractile dysfunction in a mouse model expressing a heterozygous MYBPC3 mutation associated with hypertrophic cardiomyopathy. Am J Physiol Heart Circ Physiol. 2014 Mar;306(6):H807-15 PMC3949045.

Kuster DW, Cardenas-Ospina A, Miller L, Liebetrau C, Troidl C, Nef HM, Möllmann H, Hamm CW, Pieper KS, Mahaffey KW, Kleiman NS, Stuyvers BD, Marian AJ, Sadayappan S.. Release kinetics of circulating cardiac myosin binding protein-C following cardiac injury. Am J Physiol Heart Circ Physiol. 2014 Feb 15;306(4):H547-56 PMC3920245.

Kuster DW, Sadayappan S.. MYBPC3's alternate ending: consequences and therapeutic implications of a highly prevalent 25 bp deletion mutation. Pflugers Arch. 2014 Feb;466(2):207-13. doi: 10.1007/s00424-013-1417-7 PMC3946836.

Gao X, Lin B, Sadayappan S., Patel TB. Interactions between the regulatory subunit of type I protein kinase A and p90 ribosomal S6 kinase1 regulate cardiomyocyte apoptosis. Mol Pharmacol. 2014 Feb;85(2):357-67 PMC3913359.

Sadayappan S., de Tombe PP. Cardiac myosin binding protein-C as a central target of cardiac sarcomere signaling: a special mini review series. Pflugers Arch. 2014 Feb;466(2):195-200. doi: 10.1007/s00424-013-1396-8 PMC3946865.

Khairallah RJ, Sadayappan S.. Finding the missing link: disulfide-containing proteins via a high-throughput proteomics approach. Proteomics. 2013 Nov;13(22):3245-6 PMC3923460.

Guillory AN, Yin X, Wijaya CS, Diaz Diaz AC, Rababa'h A, Singh S, Atrooz F, Sadayappan S., McConnell BK. Enhanced cardiac function in Gravin mutant mice involves alterations in the β-adrenergic receptor signaling cascade. PLoS One. 2013 Sep 18;8(9):e74784 PMC3776749.

Kuster DW, Barefield D, Govindan S, Sadayappan S.. A sensitive and specific quantitation method for determination of serum cardiac myosin binding protein-C by electrochemiluminescence immunoassay. J Vis Exp. 2013 Aug 8;(78) PMC3854717.

Lin B, Govindan S, Lee K, Zhao P, Han R, Runte KE, Craig R, Palmer BM, Sadayappan S.. Cardiac myosin binding protein-C plays no regulatory role in skeletal muscle structure and function. PLoS One. 2013 Jul 31;8(7):e69671 PMC3729691.

Govindan S, Kuster DW, Lin B, Kahn DJ, Jeske WP, Walenga JM, Leya F, Hoppensteadt D, Fareed J, Sadayappan S.. Increase in cardiac myosin binding protein-C plasma levels is a sensitive and cardiac-specific biomarker of myocardial infarction. Am J Cardiovasc Dis. 2013 Jun 10;3(2):60-70 PMC3683403.

Hwang H, Robinson D, Rogers JB, Stevenson TK, Lang SE, Sadayappan S., Day SM, Sivaramakrishnan S, Westfall MV. Agonist activated PKCβII translocation and modulation of cardiac myocyte contractile function. Sci Rep. 2013;3:1971 PMC3679501.

Jin CZ, Jang JH, Kim HJ, Wang Y, Hwang IC, Sadayappan S., Park BM, Kim SH, Jin ZH, Seo EY, Kim KH, Kim YJ, Kim SJ, Zhang YH. Myofilament Ca2+ desensitization mediates positive lusitropic effect of neuronal nitric oxide synthase in left ventricular myocytes from murine hypertensive heart. J Mol Cell Cardiol. 2013 Jul;60:107-15 PMID: 23624088.

Kuster DW, Sequeira V, Najafi A, Boontje NM, Wijnker PJ, Witjas-Paalberends ER, Marston SB, Dos Remedios CG, Carrier L, Demmers JA, Redwood C, Sadayappan S., van der Velden J. GSK3β phosphorylates newly identified site in the proline-alanine-rich region of cardiac myosin-binding protein C and alters cross-bridge cycling kinetics in human. Circ Res. 2013 Feb 15;112(4):633-9 PMC3595322.

Sequeira V, Wijnker PJ, Nijenkamp LL, Kuster DW, Najafi A, Witjas-Paalberends ER, Regan JA, Boontje N, Ten Cate FJ, Germans T, Carrier L, Sadayappan S., van Slegtenhorst MA, Zaremba R, Foster DB, Murphy AM, Poggesi C, Dos Remedios C, Stienen GJ, Ho CY, Michels M, van der Velden J. Perturbed length-dependent activation in human hypertrophic cardiomyopathy with missense sarcomeric gene mutations. Circ Res. 2013 May 24;112(11):1491-505 PMC3675884.

Guggilam A, Hutchinson KR, West TA, Kelly AP, Galantowicz ML, Davidoff AJ, Sadayappan S., Lucchesi PA. In vivo and in vitro cardiac responses to beta-adrenergic stimulation in volume-overload heart failure. J Mol Cell Cardiol. 2013 Apr;57:47-58 PMC3696990.

Sadayappan S., de Tombe PP. Cardiac myosin binding protein-C: redefining its structure and function. Biophys Rev. 2012 Jun 1;4(2):93-106 PMC3374655.

Verma SK, Krishnamurthy P, Barefield D, Singh N, Gupta R, Lambers E, Thal M, Mackie A, Hoxha E, Ramirez V, Qin G, Sadayappan S., Ghosh AK, Kishore R. 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-κB. Circulation. 2012 Jul 24;126(4):418-29 PMC3422741.

Dirkx E, Cazorla O, Schwenk RW, Lorenzen-Schmidt I, Sadayappan S., Van Lint J, Carrier L, van Eys GJ, Glatz JF, Luiken JJ. Protein kinase D increases maximal Ca2+-activated tension of cardiomyocyte contraction by phosphorylation of cMyBP-C-Ser315. Am J Physiol Heart Circ Physiol. 2012 Aug 1;303(3):H323-31 PMID: 22636676.

Hinken AC, Hanft LM, Scruggs SB, Sadayappan S., Robbins J, Solaro RJ, McDonald KS. Protein kinase C depresses cardiac myocyte power output and attenuates myofilament responses induced by protein kinase A. J Muscle Res Cell Motil. 2012 Dec;33(6):439-48 PMC3568763.

Govindan S, Sarkey J, Ji X, Sundaresan NR, Gupta MP, de Tombe PP, Sadayappan S.. Pathogenic properties of the N-terminal region of cardiac myosin binding protein-C in vitro. J Muscle Res Cell Motil. 2012 May;33(1):17-30 PMC3368277.

Sadayappan S.. Cardiac myosin binding protein-C: a potential early-stage, cardiac-specific biomarker of ischemia-reperfusion injury. Biomark Med. 2012 Feb;6(1):69-72 PMC3339268.

Howarth JW, Ramisetti S, Nolan K, Sadayappan S., Rosevear PR. Structural insight into unique cardiac myosin-binding protein-C motif: a partially folded domain. J Biol Chem. 2012 Mar 9;287(11):8254-62 PMC3318737.

van Dijk SJ, Paalberends ER, Najafi A, Michels M, Sadayappan S., Carrier L, Boontje NM, Kuster DW, van Slegtenhorst M, Dooijes D, dos Remedios C, ten Cate FJ, Stienen GJ, van der Velden J. Contractile dysfunction irrespective of the mutant protein in human hypertrophic cardiomyopathy with normal systolic function. Circ Heart Fail. 2012 Jan;5(1):36-46 PMID: 22178992.

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 PMC3246064.

Govindan S, McElligott A, Muthusamy S, Nair N, Barefield D, Martin JL, Gongora E, Greis KD, Luther PK, Winegrad S, Henderson KK, Sadayappan S.. Cardiac myosin binding protein-C is a potential diagnostic biomarker for myocardial infarction. J Mol Cell Cardiol. 2012 Jan;52(1):154-64 PMC3246118.

Palmer BM, Sadayappan S., Wang Y, Weith AE, Previs MJ, Bekyarova T, Irving TC, Robbins J, Maughan DW. Roles for cardiac MyBP-C in maintaining myofilament lattice rigidity and prolonging myosin cross-bridge lifetime. Biophys J. 2011 Oct 5;101(7):1661-9 PMC3183797.

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. 2011 Jul 8;109(2):141-50 PMC3132348.

Cuello F, Bardswell SC, Haworth RS, Ehler E, Sadayappan S., Kentish JC, Avkiran M. Novel role for p90 ribosomal S6 kinase in the regulation of cardiac myofilament phosphorylation. J Biol Chem. 2011 Feb 18;286(7):5300-10 PMC3037642.

Copeland O, Sadayappan S., Messer AE, Steinen GJ, van der Velden J, Marston SB. Analysis of cardiac myosin binding protein-C phosphorylation in human heart muscle. J Mol Cell Cardiol. 2010 Dec;49(6):1003-11 PMID: 20850451.

Senapathy P, Bhasi A, Mattox J, Dhandapany PS, Sadayappan S.. Targeted genome-wide enrichment of functional regions. PLoS One. 2010 Jun 16;5(6):e11138 PMC2886846.

Bardswell SC, Cuello F, Rowland AJ, Sadayappan S., Robbins J, Gautel M, Walker JW, Kentish JC, Avkiran M. Distinct sarcomeric substrates are responsible for protein kinase D-mediated regulation of cardiac myofilament Ca2+ sensitivity and cross-bridge cycling. J Biol Chem. 2010 Feb 19;285(8):5674-82 PMC2820795.

Barefield D, Sadayappan S.. Phosphorylation and function of cardiac myosin binding protein-C in health and disease. J Mol Cell Cardiol. 2010 May;48(5):866-75 PMID: 19962384.

Nicolaou P, Rodriguez P, Ren X, Zhou X, Qian J, Sadayappan S., Mitton B, Pathak A, Robbins J, Hajjar RJ, Jones K, Kranias EG. Inducible expression of active protein phosphatase-1 inhibitor-1 enhances basal cardiac function and protects against ischemia/reperfusion injury. Circ Res. 2009 Apr 24;104(8):1012-20 PMC2752882.

Sadayappan S., Gulick J, Klevitsky R, Lorenz JN, Sargent M, Molkentin JD, Robbins J. Cardiac myosin binding protein-C phosphorylation in a {beta}-myosin heavy chain background. Circulation. 2009 Mar 10;119(9):1253-62 PMC2656413.

Dhandapany PS, Sadayappan S., Xue Y, Powell GT, Rani DS, Nallari P, Rai TS, Khullar M, Soares P, Bahl A, Tharkan JM, Vaideeswar P, Rathinavel A, Narasimhan C, Ayapati DR, Ayub Q, Mehdi SQ, Oppenheimer S, Richards MB, Price AL, Patterson N, Reich D, Singh L, Tyler-Smith C, Thangaraj K. A common MYBPC3 (cardiac myosin binding protein C) variant associated with cardiomyopathies in South Asia. Nat Genet. 2009 Feb;41(2):187-91 PMC2697598.

Sadayappan S., Robbins J. The death of transcriptional chauvinism in the control and regulation of cardiac contractility. Ann N Y Acad Sci. 2008 Mar;1123:1-9 PMID: 18375572.

Nagayama T, Takimoto E, Sadayappan S., Mudd JO, Seidman JG, Robbins J, Kass DA. Control of in vivo left ventricular [correction] contraction/relaxation kinetics by myosin binding protein C: protein kinase A phosphorylation dependent and independent regulation. Circulation. 2007 Nov 20;116(21):2399-408 PMID: 17984378.

Yasuda S, Coutu P, Sadayappan S., Robbins J, Metzger JM. Cardiac transgenic and gene transfer strategies converge to support an important role for troponin I in regulating relaxation in cardiac myocytes. Circ Res. 2007 Aug 17;101(4):377-86 PMID: 17615373.

Sadayappan S., Finley N, Howarth JW, Osinska H, Klevitsky R, Lorenz JN, Rosevear PR, Robbins J. Role of the acidic N' region of cardiac troponin I in regulating myocardial function. FASEB J. 2008 Apr;22(4):1246-57 PMC2362400.

Krenz M, Sadayappan S., Osinska HE, Henry JA, Beck S, Warshaw DM, Robbins J. Distribution and structure-function relationship of myosin heavy chain isoforms in the adult mouse heart. J Biol Chem. 2007 Aug 17;282(33):24057-64 PMID: 17575272.

Dhandapany PS, Sadayappan S., Vanniarajan A, Karthikeyan B, Nagaraj C, Gowrishankar K, Selvam GS, Singh L, Thangaraj K. Novel mitochondrial DNA mutations implicated in Noonan syndrome. Int J Cardiol. 2007 Aug 21;120(2):284-5 PMID: 17092585.

Sadayappan S., Osinska H, Klevitsky R, Lorenz JN, Sargent M, Molkentin JD, Seidman CE, Seidman JG, Robbins J. Cardiac myosin binding protein C phosphorylation is cardioprotective. Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16918-23 PMC1636554.

Wang H, Grant JE, Doede CM, Sadayappan S., Robbins J, Walker JW. PKC-betaII sensitizes cardiac myofilaments to Ca2+ by phosphorylating troponin I on threonine-144. J Mol Cell Cardiol. 2006 Nov;41(5):823-33 PMID: 17010989.

Sadayappan S., Gulick J, Osinska H, Martin LA, Hahn HS, Dorn GW 2nd, Klevitsky R, Seidman CE, Seidman JG, Robbins J. Cardiac myosin-binding protein-C phosphorylation and cardiac function. Circ Res. 2005 Nov 25;97(11):1156-63 PMC1343494.

Annapoorani P, Dhandapany PS, Sadayappan S., Ramasamy S, Rathinavel A, Selvam GS. Cardiac isoform of alpha-2 macroglobulin-a new biomarker for myocardial infarcted diabetic patients. Atherosclerosis. 2006 May;186(1):173-6 PMID: 16102773.

Sanbe A, James J, Tuzcu V, Nas S, Martin L, Gulick J, Osinska H, Sakthivel S, Klevitsky R, Ginsburg KS, Bers DM, Zinman B, Lakatta EG, Robbins J. Transgenic rabbit model for human troponin I-based hypertrophic cardiomyopathy. Circulation. 2005 May 10;111(18):2330-8 PMC1314982.

Sakthivel S, Finley NL, Rosevear PR, Lorenz JN, Gulick J, Kim S, VanBuren P, Martin LA, Robbins J. In vivo and in vitro analysis of cardiac troponin I phosphorylation. J Biol Chem. 2005 Jan 7;280(1):703-14 PMID: 15507454.

Waldmüller S, Sakthivel S, Saadi AV, Selignow C, Rakesh PG, Golubenko M, Joseph PK, Padmakumar R, Richard P, Schwartz K, Tharakan JM, Rajamanickam C, Vosberg HP. Novel deletions in MYH7 and MYBPC3 identified in Indian families with familial hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2003 Jun;35(6):623-36 PMID: 12788380.