Abstract

The main goals of this supplemental application are: 1. To gain theoretical and practical experience dealing with human embryonic cells (hESC) both through training courses and by performing in-house experiments. 2. To develop the protocols that will allow formation of the networks of cardiomyocytes from i) uncommitted hESC and ii) cardiac-like hESC isolated from beating embryonic bodies (EB). 3. To assess the impulse propagation and excitability properties of the cardiomyocyte networks derived from the hESC. 4. To address the occurrence and development of ectopic arrhythmias in the cardiomyocyte networks derived from the hESC. Overall, we will be asking questions similar to the ones posed in our parent R01 grant (HL 076722, """"""""Origins of non-reentrant arrhythmias: ectopic nexus hypothesis"""""""", 04/01/04-03/31/08), but in relation to the networks derived from the hESC. The project will allow us to learn a great deal about the electrical properties and arrhythmogenicity of prospective cardiac grafts. The proposed experiments will be conducted using human ES cell lines listed in the NIH Human Embryonic Stem Cell Registry with NIH Code: WA01 and WA09 (Provider's Code: H1 and H9). ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
3R01HL076722-02S1
Application #
6949769
Study Section
Special Emphasis Panel (ZRG1-BDA-F (50))
Program Officer
Lathrop, David A
Project Start
2004-04-01
Project End
2008-03-31
Budget Start
2004-09-01
Budget End
2005-03-31
Support Year
2
Fiscal Year
2004
Total Cost
$76,500
Indirect Cost

  Institution

Name
George Washington University
Department
Pharmacology
Type
Schools of Medicine
DUNS #
043990498
City
Washington
State
DC
Country
United States
Zip Code
20052

  Publications

Karabekian, Zaruhi; Posnack, Nikki Gillum; Sarvazyan, Narine (2011) Immunological barriers to stem-cell based cardiac repair. Stem Cell Rev 7:315-25
Posnack, Nikki Gillum; Lee, Norman H; Brown, Ronald et al. (2011) Gene expression profiling of DEHP-treated cardiomyocytes reveals potential causes of phthalate arrhythmogenicity. Toxicology 279:54-64
Biktashev, Vadim N; Biktasheva, Irina V; Sarvazyan, Narine A (2011) Evolution of spiral and scroll waves of excitation in a mathematical model of ischaemic border zone. PLoS One 6:e24388
Asfour, Huda; Swift, Luther M; Sarvazyan, Narine et al. (2011) Signal decomposition of transmembrane voltage-sensitive dye fluorescence using a multiresolution wavelet analysis. IEEE Trans Biomed Eng 58:2083-93
House, Carrie D; Vaske, Charles J; Schwartz, Arnold M et al. (2010) Voltage-gated Na+ channel SCN5A is a key regulator of a gene transcriptional network that controls colon cancer invasion. Cancer Res 70:6957-67
Gillum, Nikki; Karabekian, Zaruhi; Swift, Luther M et al. (2009) Clinically relevant concentrations of di (2-ethylhexyl) phthalate (DEHP) uncouple cardiac syncytium. Toxicol Appl Pharmacol 236:25-38
O'Brien, Travis J; Goodsaid, Federico; Plack, Margaret et al. (2009) Development of an undergraduate pharmacogenomics curriculum. Pharmacogenomics 10:1979-86
Karabekian, Zaruhi; Gillum, Nikki D; Wong, Elissa W P et al. (2009) Effects of N-cadherin overexpression on the adhesion properties of embryonic stem cells. Cell Adh Migr 3:305-10
Biktashev, Vadim N; Arutunyan, Ara; Sarvazyan, Narine A (2008) Generation and escape of local waves from the boundary of uncoupled cardiac tissue. Biophys J 94:3726-38
Kay, Matthew; Swift, Luther; Martell, Brian et al. (2008) Locations of ectopic beats coincide with spatial gradients of NADH in a regional model of low-flow reperfusion. Am J Physiol Heart Circ Physiol 294:H2400-5

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