University of Pittsburgh
M.S., Engineering Science
University of Tennessee
B.S., Engineering Science
University of Tennessee
Associate Professor of Biomedical Engineering
Associate Professor of Pharmacology
Associate Professor of Medicine
Associate Professor of Pediatrics
Associate Chair, Department of Biomedical Engineering
Mechanobiology The first focus of the lab is in the area of mechanobiology - the study of how mechanical forces or deformations alter cellular signaling, phenotype, and biosynthetic function. More specifically, we are interested in cardiovascular mechanobiology and in particular, heart valves. We are interested in the mechano-dependent activation of fibroblasts to myofibroblasts. This work involves dynamic cell culture systems and small animal models of heart valve disease. The primary goal of this work is to elucidate the early effectors that initiate fibrotic disease. This work has been or is supported by the AHA (0835496N, 11PRE7990023, and 15PRE25710333), the NIH (K25-HL094707), and the NSF (1055384).
GPCR Targeted Drug Strategies The second focus of the lab grew out of the first and we have begun exploring potential therapeutic strategies against heart valve disease and pulmonary hypertension via serotonergic receptors. We are utilizing the lessons learned from the weight loss drug, Phen-Fen, which caused heart valve disease and pulmonary hypertension in healthy patients within 6 months. In essence, we are attempting to target the same cell surface receptors with drugs that do the reverse of what Phen-Fen did. We believe that this strategy can potentially treat age-related heart valve disease and pulmonary hypertension. This work has been or is supported by the AHA (09GRNT2010125, 10PRE4290020, and 15PRE23260021) and NIH (R01-HL115103 and F30-HL126280).
Percutaneous Interventions The third focus of the lab is the general area of percutaneous interventions for heart valve disease. In this area, we are currently developing a novel catheter for percutaneous treatment of myxomatous mitral valve disease by altering the intrinsic biomechanical compliance of the mitral valve leaflets. This work has been or is supported by the Wallace H. Coulter Foundation, the AHA (13PRE16340018), and NIH (R01-HL128715).
Tissue Engineering The fourth focus of the lab is the general area of mechanically tunable biomaterials for cardiovascular tissue engineering. We are developing tunable biomaterials that can be dynamically modified via multiple mechanisms to facilitate endothelial-to-mesenchymal transformation. This critical first step is a major roadblock in developing engineered tissues that mimic native developmental biology processes. This work has been or is supported by the AHA (12PRE12070154) and the NIH (TL1-EB008540 and T32-HL007411).
Chen J, Ryzhova LM, Sewell-Loftin MK, Brown CB, Huppert SS, Baldwin HS, and Merryman WD, “Notch1 mutation leads to valvular calcification through enhanced myofibroblast mechanotransduction”, Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 35(7): 1597-1605, 2015.
Boronyak SM, Monahan KJ, Brittain EL, Merryman WD, “An inflection point method for the determination of pulmonary transit time from contrast echocardiography”, IEEE Transactions on Biomedical Engineering, Vol. 62(7): 1853-61, 2015.
Schroer AK and Merryman WD, “Mechanobiology of myofibroblast adhesion in fibrotic cardiac disease”, Journal of Cell Science, Vol. 128(10): 1865-75, 2015.
Bloodworth NC, West JD, and Merryman WD, “Microvessel mechanobiology in pulmonary arterial hypertension: cause and effect”, Hypertension, Vol. 65(3): 483-9, 2015.
Chen J, Peacock JR, Branch JL, and Merryman WD, “Biophysical analysis of dystrophic and osteogenic models of valvular calcification”, Journal of Biomechanical Engineering, Vol. 137(2): 020903 (6 pages), 2015.
Bowler MA and Merryman WD, “In vitro models of aortic valve calcification: solidifying a system”, Cardiovascular Pathology, Vol. 24(1): 1-10, 2015.
Schroer AK, Ryzhova LM, and Merryman WD, “Network modeling approach to myofibroblast differentiation”, Cellular and Molecular Bioengineering, Vol. 7(3): 446-59, 2014.
West JD, Austin ED, Gaskill C, Marriott S, Baskir R, Bilousova G, Jean J-Ch, Hemnes AR, Menon S, Bloodworth NC, Fessel JP, Matthews MA, Kropski JA, Irwin D, Ware LB, Wheeler L, Hong CC, Meyrick B, Loyd JE, Bowman AB, Ess KC, Klemm DJ, Young PP, Merryman WD, Kotton D, and Majka SM, “Identification of a common Wnt associated genetic signature across multiple cell types in pulmonary arterial hypertension”, AJP: Cell Physiology, Vol. 307(5): C415-30, 2014.
Hutcheson JD, Aikawa E, Merryman WD, “Potential drug targets for calcific aortic valve disease”, Nature Reviews Cardiology, Vol. 11(4): 218-31, 2014.
Boronyak SM and Merryman WD, “In vitro assessment of a combined RF ablation and cryo-anchoring catheter for treatment of mitral valve prolapse”, Journal of Biomechanics, Vol. 47(5): 973-80, 2014.
Sewell-Loftin MK, DeLaughter DM, Peacock JR, Brown CB, Baldwin HS, Barnett JV, and Merryman WD, “Myocardial contraction and hyaluronic acid mechanotransduction in epithelial-to-mesenchymal transformation of endocardial cells”, Biomaterials, Vol. 35(9): 2809-15, 2014
Chen J, Drzewiecki BA, Merryman WD, Pope JC 4th, “Murine bladder compliance changes following partial bladder outlet obstruction”, Journal of Biomechanics, Vol. 46(15): 2752-5, 2013.
Merryman WD and Schoen JF, “Mechanisms of calcification in aortic valve disease: role of mechanokinetics and mechanodynamics”, Current Cardiology Reports, Vol. 15(5): 355-61, 2013.
Hutcheson JD*, Chen J*, Sewell-Loftin MK, Ryzhova LM, Fisher CI, Su YR, Merryman WD, “Cadherin-11 regulates cell-cell tension necessary for calcific nodule formation by valvular myofibroblasts”, Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 33(1): 114-20, 2013. *co-first authors.
Fisher CI*, Chen J*, Merryman WD, “Calcific nodule morphogenesis by heart valve interstitial cells is strain-dependent”, Biomechanics and Modeling in Mechanobiology, Vol. 12(1): 5-17, 2013. *co-first authors