Professor Stuart Cook is director of the genetics and genomics group that plays an integral role in the research within the Royal Brompton cardiovascular biomedical research unit.
Areas of expertise
Professor Cook’s expertise is in cardiovascular magnetic resonance imaging with a special interest in genetics in heart muscle disease.
His research focuses on the genetics of cardiovascular disease, particularly inherited cardiac conditions that cause electrical abnormalities of the heart and heart failure.
In 2011, Professor Cook and his team established the genetics and genomics group. In collaboration with world-leading laboratories, this group has developed and applied unbiased, integrated systems genetics and genomics approaches combined with high-resolution cardiovascular phenotyping to identify new genes and mechanisms for cardiac hypertrophy and dysfunction.
To date, this discovery-based research has been largely carried out in genetically tractable rat and mouse systems with translational to human tissues and cohorts as a central dogma, which has proved highly successful. In addition, the group has used genome-wide association (GWAS) in humans to identify new loci and genes for dilated cardiomyopathy (DCM), the commonest indication for heart transplantation.
Next generation sequencing technologies has enabled Professor Cook and his team to develop dedicated informatics, databases and statistical genetics to uncover new insights into heart failure biology. These advances are enabling a greater emphasis on discovery and diagnostics-based research in humans that can now be performed in cohorts of patients with inherited cardiac diseases and ischemic heart failure and control subjects phenotyped using cardiovascular magnetic resonance imaging. These cohorts will be interrogated using targeted resequencing, whole exome sequencing and whole genome sequencing in combination with conventional GWAS with bedside-to-bench translation for mechanistic studies. While these approaches are in their early stages we have already identified Titin as the commonest genetic cause of DCM, which increases the clinical diagnostic yield of DCM by up to 100%.
- Walsh R, Peters NS, Cook SA, Ware JS. Paralogue annotation identifies novel pathogenic variants in patients with Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia: J Med Genet. 2013 October; [Epub ahead of print]
- Li X, Buckton AJ, Wilkinson SL, John S, Walsh R, Novotny T, Valaskova I.Gupta M, Game L, Barton PJ, Cook SA, Ware JS. Towards clinical molecular diagnosis of inherited cardiac conditions: a comparison of bench-top genome DNA sequencers: PLoS ONE 2013 July 4;8(7),doi: 10.1371/journal.pone.0067744. Print 2013.
- Arndt AK, Schafer S, Drenckhahn JD,Sabeh MK, Plovie ER, Caliebe A, Klopocki E, Musso G, Werdich AA, Kalwa H, Heinig M, Padera RF, Wassilew K, Bluhm J, Harnack C, Martitz J, Barton PJ, Greutmann M, Berger F, Hubner N, Siebert R, Kramer HH, Cook SA, MacRae CA, Klaassen S. Fine mapping of the 1p36 deletion syndrome identifies mutation of PRDM16 as a cause of cardiomyopathy: Am J Hum Genetics 2013 July;93(1):67-77
- Ware JS, Petretto E, Cook SA. Integrative genomics in cardiovascular medicine: Cardiovasc Res 2013 March;97(4):623-630
- Ware JS, Walsh R Cunningham F, Birney E, Cook SA. Paralogous annotation of disease-causing variants in long QT syndrome genes: Hum Mutat. 2012 Aug:33(8):1188–91
- Herman DS, Lam L, Taylor MRG, Wang L, Conner L, Teekakirikul P, DePalma S, McDonough B, DL Teodorescu, Banner NJ, Barton PJR, Christodoulou D, Pennell DJ, Graw S, Merlo M, DiLenardo A, Singara G, Bos JM, Ackerman MJ, Mitchell RN, Murry CE, Lakdawala N, Ho C, Cook SA, Mestroni L, Seidman JG, Seidman CE. Structural mutation of the sarcomere protein titin are a common cause of dilated cardiomyopathy. N Eng J Med. 2012 Feb 16;366(7):619-28.
- Ware JS, Roberts AM, Cook SA. Next generation sequencing for clinical diagnostics and personalised medicine: implications for the next generation cardiologist. Heart 2012 Feb; 98(4):276-81
- McDermott-Roe C, Ye J, Ahmed R, Serafí A, Ware J, Bottolo L, Muckett P, Cañas X, Zhang J, Sun XM, Rowe GC, Buchan R, Lu H, Braithwaite A, Mancini M, Martí R, García-Arumí E, Hubner N, Jacob H, Serikawa T, Zidek V, Papousek F, Kolar F, Comella JX, Felkin LE, Barton PJR, Arany Z, Pravenec M, Petretto E, Sanchis D and Cook SA. Endonuclease G regulates mitochondrial biogenesis and cardiac hypertrophy, Nature, 2011 Oct 5; 478(7367): 114-8