Bio

Professional Education


  • Staatsexamen, Ruprecht Karl Universitat Heidelberg (2007)
  • Doctor of Medicine, Ruprecht Karl Universitat Heidelberg (2008)

Stanford Advisors


Publications

All Publications


  • Genome Editing in Cardiovascular Biology. Circulation research Seeger, T., Porteus, M., Wu, J. C. 2017; 120 (5): 778-780

    View details for DOI 10.1161/CIRCRESAHA.116.310197

    View details for PubMedID 28254802

    View details for PubMedCentralID PMC5394983

  • A Comprehensive TALEN-Based Knockout Library for Generating Human Induced Pluripotent Stem Cell-Based Models for Cardiovascular Diseases. Circulation research Karakikes, I., Termglinchan, V., Cepeda, D. A., Lee, J., Diecke, S., Hendel, A., Itzhaki, I., Ameen, M., Shrestha, R., Wu, H., Ma, N., Shao, N., Seeger, T., Woo, N. A., Wilson, K. D., Matsa, E., Porteus, M. H., Sebastiano, V., Wu, J. C. 2017

    Abstract

    Targeted genetic engineering using programmable nucleases such as transcription activator-like effector nucleases (TALENs) is a valuable tool for precise, site-specific genetic modification in the human genome.The emergence of novel technologies such as human induced pluripotent stem cells (iPSCs) and nuclease-mediated genome editing represent a unique opportunity for studying cardiovascular diseases in vitro.By incorporating extensive literature and database searches, we designed a collection of TALEN constructs to knockout 88 human genes that are associated with cardiomyopathies and congenital heart diseases. The TALEN pairs were designed to induce double-strand DNA break near the starting codon of each gene that either disrupted the start codon or introduced a frameshift mutation in the early coding region, ensuring faithful gene knockout. We observed that all the constructs were active and disrupted the target locus at high frequencies. To illustrate the utility of the TALEN-mediated knockout technique, 6 individual genes (TNNT2, LMNA/C, TBX5, MYH7, ANKRD1, and NKX2.5) were knocked out with high efficiency and specificity in human iPSCs. By selectively targeting a pathogenic mutation (TNNT2 p.R173W) in patient-specific iPSC-derived cardiac myocytes, we demonstrated that the knockout strategy ameliorates the dilated cardiomyopathy phenotype in vitro. In addition, we modeled the Holt-Oram syndrome in iPSC-cardiac myocytes in vitro and uncovered novel pathways regulated by TBX5 in human cardiac myocyte development.Collectively, our study illustrates the powerful combination of iPSCs and genome editing technologies for understanding the biological function of genes, and the pathological significance of genetic variants in human cardiovascular diseases. The methods, strategies, constructs, and iPSC lines developed in this study provide a validated, readily available resource for cardiovascular research.

    View details for DOI 10.1161/CIRCRESAHA.116.309948

    View details for PubMedID 28246128

    View details for PubMedCentralID PMC5429194

  • Efficient Genome Editing in Induced Pluripotent Stem Cells with Engineered Nucleases In Vitro. Methods in molecular biology (Clifton, N.J.) Termglinchan, V., Seeger, T., Chen, C., Wu, J. C., Karakikes, I. 2017; 1521: 55-68

    Abstract

    Precision genome engineering is rapidly advancing the application of the induced pluripotent stem cells (iPSCs) technology for in vitro disease modeling of cardiovascular diseases. Targeted genome editing using engineered nucleases is a powerful tool that allows for reverse genetics, genome engineering, and targeted transgene integration experiments to be performed in a precise and predictable manner. However, nuclease-mediated homologous recombination is an inefficient process. Herein, we describe the development of an optimized method combining site-specific nucleases and the piggyBac transposon system for "seamless" genome editing in pluripotent stem cells with high efficiency and fidelity in vitro.

    View details for PubMedID 27910041

  • MicroRNAs in cardiovascular ageing. journal of physiology Seeger, T., Boon, R. A. 2016; 594 (8): 2085-2094

    Abstract

    MicroRNAs (miRs) have emerged as potent regulators of pathways in physiological and disease contexts. This review focuses on the role of miRs in ageing of the cardiovascular system. Several miRs have been described to be regulated during ageing and some of these miRs are involved in the regulation of ageing-related processes. We discuss the roles of miR-34, miR-217 and miR-29, which are induced during ageing in the vasculature. The roles of miR-34, miR-29 (age-induced) and miR-18/19, which are decreased during ageing in the heart, are discussed as well. Furthermore, numerous miRs that play a role in diseases associated with ageing, like diabetes, atherosclerosis, hypertension, cardiac hypertrophy and atrial fibrillation, are also briefly discussed. miRs also serve as circulating biomarkers for cardiovascular ageing or ageing-associated diseases. Finally, pharmacological modulation of ageing-related miRs might become a promising strategy to combat cardiovascular ageing in a clinical setting.

    View details for DOI 10.1113/JP270557

    View details for PubMedID 26040259

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