"My research aims to seek a mechanistic understanding of diastolic pathology in heart failure with preserved ejection fraction (HFpEF) and identify its therapeutic targets. I approach HFpEF from the perspective of the myofilaments. My ongoing projects focus on the effect of menopause on HFpEF development and the reno-sarcomeric interplay in chronic kidney disease (CKD)-induced HFpEF."
Original Peer-Review Publications
1. de Winter JM, Bouman K, Strom J, Methawasin M, Jongbloed JDH, van der Roest W, Wijngaarden JV,
Timmermans J, Nijveldt R, van den Heuvel F, Kamsteeg EJ, van Engelen BG, Galli R, Bogaards SJP, Boon
RA, van der Pijl RJ, Granzier H, Koeleman B, Amin AS, van der Velden J, van Tintelen JP, van den Berg
MP, van Spaendonck-Zwarts KY, Voermans NC, Ottenheijm CAC. KBTBD13 is a novel cardiomyopathy
gene. Hum Mutat. 2022 Dec;43(12):1860-1865. PMID: 36335629; PMCID: PMC10100581.
2. Wang C, Zhang Y, Methawasin M, Braz CU, Gao-Hu J, Yang B, Strom J, Gohlke J, Hacker T, Khatib H,
Granzier H, Guo W. RBM20(S639G) mutation is a high genetic risk factor for premature death through RNAprotein
condensates. J Mol Cell Cardiol. 2022 Apr;165:115-129. PMID: 35041844; PMCID: PMC8940686.
3. Methawasin M*, Farman GP, Granzier-Nakajima S, Strom J, Kiss B, Smith JE 3rd, Granzier H. Shortening
the thick filament by partial deletion of titin's C-zone alters cardiac function by reducing the operating
sarcomere length range. J Mol Cell Cardiol. 2022 Apr;165:103-114. PMID: 35031281; PMCID:
PMC8940690. *corresponding author
4. Goto K, Schauer A, Augstein A, Methawasin M, Granzier H, Halle M, Craenenbroeck EMV, Rolim N, Gielen
S, Pieske B, Winzer EB, Linke A, Adams V. Muscular changes in animal models of heart failure with
preserved ejection fraction: what comes closest to the patient?. ESC Heart Fail. 2021 Feb;8(1):139-
150. PMID: 33350094; PMCID: PMC7835579.
5. Methawasin M, Strom J, Borkowski T, Hourani Z, Runyan R, Smith JE 3rd, Granzier H. Phosphodiesterase
9a Inhibition in Mouse Models of Diastolic Dysfunction. Circ Heart Fail. 2020 May;13(5):e006609. PMID:
32418479; PMCID: PMC7895451.
Editorial commentary by Blanton RM. Phosphodiesterase 9 Inhibition in Models of Heart Failure
With Preserved Left Ventricular Ejection Fraction. Should We Focus on the Positive or Negative?
Circ Heart Fail. 2020 May;13(5): e007107. PMID: 32418477
6. Yousefi K, Irion CI, Takeuchi LM, Ding W, Lambert G, Eisenberg T, Sukkar S, Granzier HL, Methawasin M,
Lee DI, Hahn VS, Kass DA, Hatzistergos KE, Hare JM, Webster KA, Shehadeh LA. Osteopontin Promotes
Left Ventricular Diastolic Dysfunction Through a Mitochondrial Pathway. J Am Coll Cardiol. 2019 Jun
4;73(21):2705-2718. PMID: 31146816; PMCID: PMC6546303.
7. Radke MH, Polack C, Methawasin M, Fink C, Granzier HL, Gotthardt M. Deleting Full Length Titin Versus
the Titin M-Band Region Leads to Differential Mechanosignaling and Cardiac Phenotypes. Circulation. 2019
Apr 9;139(15):1813-1827. PMID: 30700140; PMCID: PMC6453709.
8. Slater RE, Strom JG, Methawasin M, Liss M, Gotthardt M, Sweitzer N, Granzier HL. Metformin improves
diastolic function in an HFpEF-like mouse model by increasing titin compliance. J Gen Physiol. 2019 Jan
7;151(1):42-52. PMID: 30567709; PMCID: PMC6314384.
9. Li KL, Methawasin M, Tanner BCW, Granzier HL, Solaro RJ, Dong WJ. Sarcomere length-dependent effects
on Ca2+-troponin regulation in myocardium expressing compliant titin. J Gen Physiol. 2019 Jan 7;151(1):30-
41. PMID: 30523116; PMCID: PMC6314383.
10. Tonino P, Kiss B, Strom J, Methawasin M, Smith JE 3rd, Kolb J, Labeit S, Granzier H. The giant protein titin
regulates the length of the striated muscle thick filament. Nat Commun. 2017 Oct 19;8(1):1041. PMID:
29051486; PMCID: PMC5648799.
11. Methawasin M, Strom JG, Slater RE, Fernandez V, Saripalli C, Granzier H. Experimentally Increasing the
Compliance of Titin Through RNA Binding Motif-20 (RBM20) Inhibition Improves Diastolic Function In a
Mouse Model of Heart Failure With Preserved Ejection Fraction. Circulation. 2016 Oct 11;134(15):1085-
1099. PMID: 27630136; PMCID: PMC5069184.
Editorial commentary by LeWinter MM, Zile MR. Could Modification of Titin Contribute to an Answer
for Heart Failure With Preserved Ejection Fraction? Circulation. 2016 Oct 11;134 (15):1100-
1104. PMID: 27630137
12. Bull M, Methawasin M, Strom J, Nair P, Hutchinson K, Granzier H. Alternative Splicing of Titin Restores
Diastolic Function in an HFpEF-Like Genetic Murine Model (TtnΔIAjxn). Circ Res. 2016 Sep 2;119(6):764-
72. PMID: 27470639; PMCID: PMC5059842.
13. Kolb J, Li F, Methawasin M, Adler M, Escobar YN, Nedrud J, Pappas CT, Harris SP, Granzier H. Thin
filament length in the cardiac sarcomere varies with sarcomere length but is independent of titin and
nebulin. J Mol Cell Cardiol. 2016 Aug;97:286-94. PMID: 27139341; PMCID: PMC5584371.
14. Pulcastro HC, Awinda PO, Methawasin M, Granzier H, Dong W, Tanner BC. Increased Titin Compliance
Reduced Length-Dependent Contraction and Slowed Cross-Bridge Kinetics in Skinned Myocardial Strips
from Rbm (20ΔRRM) Mice. Front Physiol. 2016;7:322. PMID: 27524973; PMCID: PMC4966298.
15. Granzier HL, Hutchinson KR, Tonino P, Methawasin M, Li FW, Slater RE, Bull MM, Saripalli C, Pappas CT,
Gregorio CC, Smith JE 3rd. Deleting titin's I-band/A-band junction reveals critical roles for titin in
biomechanical sensing and cardiac function. Proc Natl Acad Sci USA. 2014 Oct 7;111(40):14589-94. PMID:
25246556; PMCID: PMC4210014.
16. Methawasin M, Hutchinson KR, Lee EJ, Smith JE 3rd, Saripalli C, Hidalgo CG, Ottenheijm CA, Granzier
H. Experimentally increasing titin compliance in a novel mouse model attenuates the Frank-Starling
mechanism but has a beneficial effect on diastole. Circulation. 2014 May 13;129(19):1924-36. PMID:
24599837; PMCID: PMC4032222.
17. Chung CS, Hutchinson KR, Methawasin M, Saripalli C, Smith JE 3rd, Hidalgo CG, Luo X, Labeit S, Guo C,
Granzier HL. Shortening of the elastic tandem immunoglobulin segment of titin leads to diastolic
dysfunction. Circulation. 2013 Jul 2;128(1):19-28. PMID: 23709671; PMCID: PMC3822017.
18. Hidalgo CG, Chung CS, Saripalli C, Methawasin M, Hutchinson KR, Tsaprailis G, Labeit S, Mattiazzi A,
Granzier HL. The multifunctional Ca2+/calmodulin-dependent protein kinase II delta (CaMKIIδ)
phosphorylates cardiac titin's spring elements. J Mol Cell Cardiol. 2013 Jan;54:90-7. PMID: 23220127;
PMCID: PMC3535572.
19. Chung CS, Methawasin M, Nelson OL, Radke MH, Hidalgo CG, Gotthardt M, Granzier HL. Titin based
viscosity in ventricular physiology: an integrative investigation of PEVK-actin interactions. J Mol Cell
Cardiol. 2011 Sep;51(3):428-34. PMID: 21708170; PMCID: PMC3150406.
20. King NM*, Methawasin M*, Nedrud J, Harrell N, Chung CS, Helmes M, Granzier H. Mouse intact cardiac
myocyte mechanics: cross-bridge and titin-based stress in unactivated cells. J Gen Physiol. 2011
Jan;137(1):81-91. PMID: 21187335; PMCID: PMC3010058. * equal contribution
21. Charoenphandhu N, Teerapornpuntakit J, Methawasin M, Wongdee K, Thongchote K, Krishnamra
N. Prolactin decreases expression of Runx2, osteoprotegerin, and RANKL in primary osteoblasts derived
from tibiae of adult female rats. Can J Physiol Pharmacol. 2008 May;86(5):240-8. PMID: 18432284.