“We combine quantitative imaging of the human heart and vasculature with common and rare variant genetic analyses and genomic studies to understand cardiovascular biology and disease”

We leverage both the power of genomewide genotyping of millions of single nucleotide polymorphisms and the high fidelity and quantitative aspects of cardiovascular magnetic resonance (CMR) imaging to identify genetic determinants of human cardiovascular disease.We have developed a large cohort of healthy volunteers phenotyped in detail for cardiovascular traits using 3D CMR imaging, with Dr O’Regan. These studies are carried out in collaboration with the Sanger Institute (Dr Birney) and Imperial College London (Dr Rueckert).In addition, we carry out linkage and association studies of human cardiovascular disease in patients and families phenotyped by CMR imaging. We recently discovered that mutations in titin (TTN) are the commonest cause of inherited heart failure, and the Group is now integrating genetic studies of TTN with detailed CMR imaging in patients and controls.These studies are complemented by RNA sequencing of the human heart and protein-protein interactomes that enable us to build gene networks (in collaboration with Dr Petretto – Integrative Genomics and Medicine) and define biological pathways, with the aim of uncovering novel mechanisms, diagnostics and therapeutic targets.

Find out more about our latest group member James Ware, and read about his recent seminar.

Selected Publications

Maatz, H., Jens, M., Liss, M., Schafer, S., Heinig, M., Kirchner, M., Adami, E., Rintisch, C., Dauksaite, V., Radke, M. H., Selbach, M., Barton, P. J., Cook, S. A., Rajewsky, N., Gotthardt, M., Landthaler, M., & Hubner, N. (2014). RNA-binding protein RBM20 represses splicing to orchestrate cardiac pre-mRNA processing. The Journal of Clinical Investigation, 124(8), 3419–3430.

Arndt, A.-K. K., Schafer, S., Drenckhahn, J.-D. D., Sabeh, M. K., Plovie, E. R., Caliebe, A., Klopocki, E., Musso, G., Werdich, A. A., Kalwa, H., Heinig, M., Padera, R. F., Wassilew, K., Bluhm, J., Harnack, C., Martitz, J., Barton, P. J., Greutmann, M., Berger, F., Hubner, N., Siebert, R., Kramer, H.-H. H., Cook, S. A., MacRae, C. A., & Klaassen, S. (2013). Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy. American Journal of Human Genetics, 93(1), 67–77.

Ware, J. S., Walsh, R., Cunningham, F., Birney, E., & Cook, S. A. (2012). Paralogous annotation of disease-causing variants in long QT syndrome genes. Human Mutation, 33(8), 1188–1191.

Herman, D. S., Lam, L., Taylor, M. R., Wang, L., Teekakirikul, P., Christodoulou, D., Conner, L., DePalma, S. R., McDonough, B., Sparks, E., Teodorescu, D. L. L., Cirino, A. L., Banner, N. R., Pennell, D. J., Graw, S., Merlo, M., Di Lenarda, A., Sinagra, G., Bos, J. M., Ackerman, M. J., Mitchell, R. N., Murry, C. E., Lakdawala, N. K., Ho, C. Y., Barton, P. J., Cook, S. A., Mestroni, L., Seidman, J. G., & Seidman, C. E. (2012). Truncations of titin causing dilated cardiomyopathy. The New England Journal of Medicine, 366(7), 619–628.

McDermott-Roe, C., Ye, J., Ahmed, R., Sun, X.-M. M., Serafı́n, A., Ware, J., Bottolo, L., Muckett, P., Cañas, X., Zhang, J., Rowe, G. C., Buchan, R., Lu, H., Braithwaite, A., Mancini, M., Hauton, D., Martı́, R., Garcı́a-Arumı́, E., Hubner, N., Jacob, H., Serikawa, T., Zidek, V., Papousek, F., Kolar, F., Cardona, M., Ruiz-Meana, M., Garcı́a-Dorado, D., Comella, J. X., Felkin, L. E., Barton, P. J., Arany, Z., Pravenec, M., Petretto, E., Sanchis, D., & Cook, S. A. (2011). Endonuclease g is a novel determinant of cardiac hypertrophy and mitochondrial function. Nature, 478(7367), 114–118.

Heinig, M., Petretto, E., Wallace, C., Bottolo, L., Rotival, M., Lu, H., Li, Y., Sarwar, R., Langley, S. R., Bauerfeind, A., Hummel, O., Lee, Y.-A. A., Paskas, S., Rintisch, C., Saar, K., Cooper, J., Buchan, R., Gray, E. E., Cyster, J. G., Cardiogenics Consortium, Erdmann, J., Hengstenberg, C., Maouche, S., Ouwehand, W. H., Rice, C. M., Samani, N. J., Schunkert, H., Goodall, A. H., Schulz, H., Roider, H. G., Vingron, M., Blankenberg, S., Münzel, T., Zeller, T., Szymczak, S., Ziegler, A., Tiret, L., Smyth, D. J., Pravenec, M., Aitman, T. J., Cambien, F., Clayton, D., Todd, J. A., Hubner, N., & Cook, S. A. (2010). A trans-acting locus regulates an anti-viral expression network and type 1 diabetes risk. Nature, 467(7314), 460–464.

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