Research Groups > Genes and Metabolism Molecular Cardiology
The group uses genetics, genomics, integrative physiology and cardiac imaging to study the molecular basis of heart failure.
Heart failure is a disease of epidemic proportions that affects 14 million people in the EU and is more prevalent and associated with a worse prognosis than most common cancers. The molecular mechanisms leading to systolic and diastolic heart failure are poorly understood and are the main focus of the group. The group has applied integrated genetic and genomic studies to identify the genetic control points for thousands of genes in the rat heart that can now be used to unravel the complex mechanisms underlying heart failure. Translational studies are central research activities of the group and our genomic studies of human heart biopsies have clearly demonstrated the power of combined model organism and human studies. With the availability of next generation sequencing technologies at the MRC-CSC the group will increasingly apply massive parallel sequencing to uncover the new genomic insights for heart failure that will be tested using state-of-the-art functional genomic loss- and gain-of-function approaches. The overall aim of the group, which comprises of physician scientists, molecular and cell biologists with strong bioinformatic and statistical genetic support (see Dr. Enrico Petretto's homepage), is to identify candidate genes for human heart failure with a view to revealing new biology and therapeutic targets.
Figure 1. Quantitative trait transcripts analysis. Transcripts under genetic control (eQTLs) were correlated with left ventricular mass index (LVMI) in recombinant inbred rat strains. Expression profiles of 1,444 eQTLs (PGW = 0.05) were correlated with values of LVMI, in the BXH/HXB RI strain panel. The absolute Pearson correlation coefficient with LVMI is plotted against the location of the probeset (Mb). (click here for large version of image)
Figure 2. Inferior myocardial infarction in a patient following primary angioplasty at Imperial College Healthcare NHS Trust. Images were acquired using gadolinium-enhanced, inversion recovery cardiac MRI and were visualized using post-processing. The regions of the heart that survived the heart attack are black whereas infarcted and inflamed heart tissue is shown in orange.
An organisatinal chart can be downloaded from here
Figure 1. Quantitative trait transcripts analysis. Transcripts under genetic control (eQTLs) were correlated with left ventricular mass index (LVMI) in recombinant inbred rat strains. Expression profiles of 1,444 eQTLs (PGW = 0.05) were correlated with values of LVMI, in the BXH/HXB RI strain panel. The absolute Pearson correlation coefficient with LVMI is plotted against the location of the probeset (Mb). (click here for large version of image)
Figure 2. Inferior myocardial infarction in a patient following primary angioplasty at Imperial College Healthcare NHS Trust. Images were acquired using gadolinium-enhanced, inversion recovery cardiac MRI and were visualized using post-processing. The regions of the heart that survived the heart attack are black whereas infarcted and inflamed heart tissue is shown in orange.
Group head
Stuart Cook (Professor)
Telephone 31346
Email
Group members
Adam Braithwaite (Mr)
Rachel Buchan (Miss)
Telephone 38313
Email
Tamara Diamond (Miss)
Han Lu (Ms)
Telephone 38537/31770
Email
Chris McDermott-Roe (Dr)
Telephone 38537/31770
Philip Muckett (Mr)
Telephone 38537/31770
Email
Bhakti Patel (Dr)
Xi-Ming Sun (Dr)
Anabel Varela Carver (Dr)
James Ware (Dr)
Samuel Wilkinson (Mr)
Admin contact
Sabika Ali (Mrs)
Telephone 38288
Contact details
Telephone: +44 (0) 20 8383 1346
Facsimile: +44 (0) 20 8383 8577
Facsimile: +44 (0) 20 8383 8577
Selected publications
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, 460–464. Abstract
Petretto, E., Bottolo, L., Langley, S. R., Heinig, M., McDermott-Roe, C., Sarwar, R., Pravenec, M., Hübner, N., Aitman, T. J., Cook, S. A., Richardson, S., April 2010. New insights into the genetic control of gene expression using a bayesian multi-tissue approach. PLoS computational biology 6, e1000737+. Abstract
Cook, S. A., Varela-Carver, A., Mongillo, M., Kleinert, C., Khan, M. T., Leccisotti, L., Strickland, N., Matsui, T., Das, S., Rosenzweig, A., Punjabi, P., Camici, P. G. (2010). Abnormal myocardial insulin signalling in type 2 diabetes and left-ventricular dysfunction. European heart journal 31, 100–111. Abstract
Cook, S. A., Clerk, A. & Sugden, P. H. (2008). Are transgenic mice the 'alkahest' to understanding myocardial hypertrophy and failure? Journal of Molecular and Cellular Cardiology 46, 118–129. Abstract
Petretto, E., Sarwar, R., Grieve, I., Lu, H., Kumaran, M. K., Muckett, P. J., Mangion, J., Schroen, B., Benson, M., Punjabi, P. P., Prasad, S. K., Pennell, D. J., Kiesewetter, C., Tasheva, E. S., Corpuz, L. M., Webb, M. D., Conrad, G. W., Kurtz, T. W., Kren, V., Fischer, J., Hubner, N., Pinto, Y. M., Pravenec, M., Aitman, T. J. & Cook, S. A. (2008). Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass. Nature Genetics 40, 546–542. Abstract | Full text
Petretto, E., Mangion, J., Dickens, N. J., Cook, S. A., Kumaran, M. K., Lu, H., Fischer, J., Maatz, H., Kren, V., Pravenec, M., Hubner, N. & Aitman, T. J. (2006). Heritablity and tissue specificity of expression quantitative trait loci. PLoS Genetics 2, e172. Abstract | Full text
Petretto, E., Bottolo, L., Langley, S. R., Heinig, M., McDermott-Roe, C., Sarwar, R., Pravenec, M., Hübner, N., Aitman, T. J., Cook, S. A., Richardson, S., April 2010. New insights into the genetic control of gene expression using a bayesian multi-tissue approach. PLoS computational biology 6, e1000737+. Abstract
Cook, S. A., Varela-Carver, A., Mongillo, M., Kleinert, C., Khan, M. T., Leccisotti, L., Strickland, N., Matsui, T., Das, S., Rosenzweig, A., Punjabi, P., Camici, P. G. (2010). Abnormal myocardial insulin signalling in type 2 diabetes and left-ventricular dysfunction. European heart journal 31, 100–111. Abstract
Cook, S. A., Clerk, A. & Sugden, P. H. (2008). Are transgenic mice the 'alkahest' to understanding myocardial hypertrophy and failure? Journal of Molecular and Cellular Cardiology 46, 118–129. Abstract
Petretto, E., Sarwar, R., Grieve, I., Lu, H., Kumaran, M. K., Muckett, P. J., Mangion, J., Schroen, B., Benson, M., Punjabi, P. P., Prasad, S. K., Pennell, D. J., Kiesewetter, C., Tasheva, E. S., Corpuz, L. M., Webb, M. D., Conrad, G. W., Kurtz, T. W., Kren, V., Fischer, J., Hubner, N., Pinto, Y. M., Pravenec, M., Aitman, T. J. & Cook, S. A. (2008). Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass. Nature Genetics 40, 546–542. Abstract | Full text
Petretto, E., Mangion, J., Dickens, N. J., Cook, S. A., Kumaran, M. K., Lu, H., Fischer, J., Maatz, H., Kren, V., Pravenec, M., Hubner, N. & Aitman, T. J. (2006). Heritablity and tissue specificity of expression quantitative trait loci. PLoS Genetics 2, e172. Abstract | Full text
