Laboratory of William C. Claycomb
PhD, Indiana University, 1969

Claycomb Lab Photo, Dec. 2006: Front Row: William Claycomb & May Lam Top Row: Brenda Royals & Peng Gao

The major interest of this laboratory is to develop mechanisms to repair or regenerate heart muscle tissue in the diseased heart. We are taking two major approaches. One is to understand the molecular machinery in which Nature restricts and irreversibly inhibits heart cell division during early development so that we can design procedures to reinitiate cell division to essentially regenerate muscle tissue. The other approach is to actually transplant heart muscle cells back into the diseased heart to repair or replace the injured muscle cells. Presently we are using mouse embryonic stem cells (ES Cells) to derive immortalized ventricular, atrial and conducting heart cell lines that retain a cardiac lineage-specific phenotype. This involves using a combinatorial selection process with multiple promoters and selectable markers. The idea is to create three different types of heart muscle cells that could be grown continuously in culture and be used as model systems to study the function and dysfunction of the ventricle, atria and conduction system of the heart. We have recently been successful in utilizing specific molecular markers to identify a primitive cardiac conduction system utilizing differentiating ES cells in embryoid bodies. We are also utilizing these genetically engineered ES cells in a tissue-engineering project. These cells would be extremely useful as research reagents for basic cardiac muscle cell research such as growth regulation and signal transduction as well as for therapeutic applications such as transplantation of cells into a diseased heart to repair damaged heart muscle and as a cell replacement therapy to treat a wide variety of cardiomyopathies.

Recent Publications

Shimko VF, Claycomb WC., Effect of Mechanical Loading on Three-Dimensional Cultures of Embryonic Stem Cell-Derived Cardiomyocytes., Tissue Eng. (2008)

Landstrom AP, Weisleder N, Batalden KB, Martijn Bos J, Tester DJ, Ommen SR, Wehrens XH, Claycomb WC, Ko JK, Hwang M, Pan Z, Ma J, Ackerman MJ., Mutations in JPH2-encoded junctophilin-2 associated with hypertrophic cardiomyopathy in humans., J Mol Cell Cardiol., Apr 18. (2007)

George CH, Rogers SA, Bertrand BM, Tunwell RE, Thomas NL, Steele DS, Cox EV, Pepper C, Hazeel CJ, Claycomb WC, Lai FA. Alternative Splicing of Ryanodine Receptors Modulates Cardiomyocyte Ca2+ Signaling and Susceptibility to Apoptosis. Circ Res. Feb. 22; (2007)

Hidalgo-Bastida LA, Barry JJ, Everitt NM, Rose FR, Buttery LD, Hall IP, Claycomb WC, Shakesheff KM. Cell adhesion and mechanical properties of a flexible scaffold for cardiac tissue engineering. Acta Biomater. Feb. 26; (2007)

White SM, Claycomb WC. Embryonic stem cells form an organized, functional cardiac conduction system in vitro. Am J Physiol Heart Circ Physiol. Feb.;288(2):H670-9 (2005) Open PDF of this article

Barnes K, Dobrzynski H, Foppolo S, Beal PR, Ismat F, Scullion ER, Sun L, Tellez J, Ritzel MW, Claycomb WC, Cass CE, Young JD, Billeter-Clark R, Boyett MR, Baldwin SA. Distribution and Functional Characterization of Equilibrative Nucleoside Transporter-4, a Novel Cardiac Adenosine Transporter Activated at Acidic pH. Circ Res. Jul. 27. (2006) View Abstract

Filipeanu CM, Zhou F, Lam ML, Kerut KE, Claycomb WC, Wu G. Enhancement of the recycling and activation of beta-adrenergic receptor by Rab4 GTPase in cardiac myocytes. J Biol Chem., Apr 21;281(16):11097-103 (2006) Open PDF of this article

Ikeda K, Tojo K, Otsubo C, Udagawa T, Kumazawa K, Ishikawa M, Tokudome G,Hosoya T, Tajima N, Claycomb WC, Nakao K, Kawamura M. 5-hydroxytryptamine synthesis in HL-1 cells and neonatal rat cardiocytes. Biochem Biophys Res Commun. Mar. 11;328(2):522-5 (2005) Open PDF of this article

Chandrasekar B, Mummidi SM, Claycomb WC, Mestril R, Nemer MD. Interleukin-18 is a pro-hypertrophic cytokine that acts through a phosphatidylinositol 3-kinase- phosphoinositide-dependent kinase-1-Akt-GATA4 signaling pathway in cardiomyocytes. J Biol Chem. Dec 1; (2004) Open PDF of this article

Filipeanu CM, Zhou F, Claycomb WC, Wu G. Regulation of the cell-surface expression and function of angiotensin II type 1 receptor by Rab1-mediated ER-to-Golgi transport in cardiac myocytes. J Biol Chem. Sep. 24;279(39):41077-84 (2004) Open PDF of this article

White SM, Constantin PE, Claycomb WC. Cardiac physiology at the cellular level: use of cultured HL-1 cardiomyocytes for studies of cardiac muscle cell structure and function. Am J Physiol Heart Circ Physiol., Mar;286(3):H823-9 (2004) Open PDF of this article

Seymour EM, Wu SY, Kovach MA, Romano MA, Traynor JR, Claycomb WC, Bolling SF. HL-1 myocytes exhibit PKC and K(ATP) channel-dependent delta opioid preconditioning. J Surg Res.Oct;114(2):187-94 (2003) Open PDF of this article

White SM, Claycomb WC. Cardiac cell transplantation: protocols and applications. Methods Mol Biol., ;219:83-95. (2003) No abstract or PDF available

Lam ML, Bartoli M, Claycomb WC. The 21-day postnatal rat ventricular cardiac muscle cell in culture as an experimental model to study adult cardiomyocyte gene expression. Mol Cell Biochem., Jan.;229(1-2):51-62. (2002) Open PDF of this article

Neilan CL, Kenyon E, Kovach MA, Bowden K, Claycomb WC, Traynor JR, Bolling SF. An immortalized myocyte cell line, HL-1, expresses a functional delta –opioid receptor. J Mol Cell Cardiol., Dec;32(12):2187-93. (2000) Open PDF of this article

Lanson NA Jr, Egeland DB, Royals BA, Claycomb WC. The MRE11-NBS1-RAD50 pathway is perturbed in SV40 large T antigen-immortalized AT-1, AT-2 and HL-1 cardiomyocytes. Nucleic Acids Res., Aug. 1;28(15):2882-92.(2000) Open PDF of this article

Nguyen SV, Claycomb WC. Hypoxia regulates the expression of the adrenomedullin and HIF-1 genes in cultured HL-1 cardiomyocytes.Biochem Biophys Res Commun. Nov 19;265(2):382-6. (1999) Open PDF of this article

Cormier-Regard S, Nguyen SV, Claycomb WC. Adrenomedullin gene expression is developmentally regulated and induced byhypoxia in rat ventricular cardiac myocytes. J Biol Chem., Jul. 10;273(28):17787-92. (1998) Open PDF of this article

Watanabe E, Smith DM Jr, Delcarpio JB, Sun J, Smart FW, Van Meter CH Jr, Claycomb WC. Cardiomyocyte transplantation in a porcine myocardial infarction model. Cell Transplant, May-Jun.;7(3):239-46. (1998) View Abstract

Claycomb WC, Lanson NA Jr, Stallworth BS, Egeland DB, Delcarpio JB, Bahinski A, Izzo NJ Jr. HL-1 cells: a cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte. Proc Natl Acad Sci U S A., 1998 Mar. 17;95(6):2979-84. Open PDF of this article

Watanabe E, Smith DM, Sun J, Smart FW, Delcarpio JB, Roberts TB, Van Meter CH Jr, Claycomb WC. Effect of basic fibroblast growth factor on angiogenesis in the infarcted porcine heart. Basic Res Cardiol. Feb;93(1):30-7.(1998) Open PDF of this article

Cormier-Regard S, Egeland DB, Tannoch VJ, Claycomb WC. Differential display: identifying genes involved in cardiomyocyte proliferation. Mol Cell Biochem.,Jul;172(1-2):111-20. (1997) View Abstract

Bartoli M, Claycomb WC. Transfer of macromolecules into living adult cardiomyocytes by microinjection. Mol Cell Biochem., Jul;172(1-2):103-9.(1997)View Abstract

Smith DM Jr, Claycomb WC. Adult rat cardiomyocyte proliferation assay. In Vitro Cell Dev Biol Anim., Jun;33(6):428-31. (1997) No abstract available

Chen YF, Durand J, Claycomb WC. Hypoxia stimulates atrial natriuretic peptide gene expression in cultured atrial cardiocytes. Hypertension, Jan;29(1 Pt 1):75-82. (1997) View Abstract

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