ProfessorJamesWare

Faculty of Medicine, National Heart & Lung Institute

Professor of Cardiovascular and Genomic Medicine

Contact

j.ware Website

Assistant

Ms Lisa Quinn +44 (0)20 7594 1345

Location

3 13GLMS BuildingHammersmith Campus

Summary

James Ware is a Professor of Cardiovascular and Genomic Medicine at Imperial College London, MRC Investigator at the MRC Laboratory of Medical Sciences, and Honorary Consultant Cardiologist at Royal Brompton and Harefield Hospitals, and at Imperial College Hospitals. His research group spans the National Heart & Lung Institute, the MRC London Institute of Medical Sciences, the NIHR Imperial Biomedical Research Centre, the BHF Imperial Centre of Research Excellence, and the Royal Brompton Cardiovascular Research Centre. The group's work is supported by the Sir Jules Thorn Charitable Trust, the Wellcome Trust, the Medical Research Council, the British Heart Foundation, the National Institute for Health Research, the US National Institutes for Health, the NHLI Foundation, and Cardiomyopathy UK. James also has a visiting position at the Broad Institute of MIT and Harvard.

James’ overarching research aims are to understand the impact of genetic variation on the heart and circulation, and to use genome information to improve patient care.

Research

Understanding the genetic architecture of cardiomyopathies – we are using genetic & genomic approaches to understand the genetic underpinnings of heritable heart muscle diseases in humans. We are using exome and genome sequencing approaches to find genes that cause Mendelian (single-gene) forms of these diseases, and are also exploring the role of more common genetic and environmental factors that modulate disease risk and severity. These studies both provide diagnostic answers to affected families, and also identify potential new therapeutic targets.

We have also launched a community web portal - the heart hive - to support patient participation in research into heart muscle disease, allowing participants to self-enrol in our research, and to see what other research opportunities are available.

Variant interpretation – all of us carry rare variants that alter important genes. Distinguishing between those that cause disease and those that are innocent bystanders is a key challenge in contemporary clinical genetics. We are developing and applying new methods to address this challenge, and collaborating globally to refine our understanding of variation in genes associated with heart disease.

Precision medicine – we are evaluating the use of genetic and other biomarkers to stratify patients and predict their response to therapy and long-term outcomes. Ultimately, we are working to interpret genome information so that it can be used to optimise treatment choice for our patients.

Titin – we have a particular focus on the Titin gene, which encodes the largest human protein, a key component of muscles throughout the body. Recently identified as the most important cause of inherited dilated cardiomyopathy, we are working to understand the effects of Titin variants on the heart, their mechanisms of action, and their clinical significance.

Software - web resources, software, and other tools developed by the group are available here.

Clinical

In the clinic, James is a Cardiologist specializing in the diagnosis and management of inherited cardiac conditions, including cardiomyopathies and inherited arrhythmia syndromes. This includes the assessment of families in which there has been a sudden unexplained death, in which case it is important to look for an underlying genetic condition that may also affect surviving relatives. For referral information please follow the links for NHS (UK) or private (UK or international) patients.

Biography

Dr Ware graduated from the University of Cambridge in 2000, and pursued general medical training in Cambridge, London and Geneva before appointment to specialist training in Cardiology in 2007. After a PhD at the MRC Clinical Sciences Centre (CSC), funded by a Fellowship from the Wellcome Trust, he was appointed an NIHR Clinical Lecturer in 2012, and undertook post-doctoral research at the MRC CSC, Imperial College, Harvard Medical School, and the Broad Institute. He was awarded a Wellcome Trust Intermediate Clinical Fellowship in 2015 and returned from Boston to start his own research group.

Selected Publications

Journal Articles

Wilde AAM, Semsarian C, Márquez MF, et al.Wilde AAM, Semsarian C, Márquez MF, Sepehri Shamloo A, Ackerman MJ, Ashley EA, Sternick EB, Barajas-Martinez H, Behr ER, Bezzina CR, Breckpot J, Charron P, Chockalingam P, Crotti L, Gollob MH, Lubitz S, Makita N, Ohno S, Ortiz-Genga M, Sacilotto L, Schulze-Bahr E, Shimizu W, Sotoodehnia N, Tadros R, Ware JS, Winlaw DS, Kaufman ES, ESC Scientific Document Group close, 2022, European Heart Rhythm Association (EHRA)/Heart Rhythm Society (HRS)/Asia Pacific Heart Rhythm Society (APHRS)/Latin American Heart Rhythm Society (LAHRS) Expert Consensus Statement on the state of genetic testing for cardiac diseases, Europace, Vol:38, ISSN:1099-5129, Pages:491-553

McGurk KA, Zheng SL, Henry A, et al.McGurk KA, Zheng SL, Henry A, Josephs K, Edwards M, de Marvao A, Whiffin N, Roberts A, Lumbers TR, O'Regan DP, Ware JS close, 2022, Correspondence on "ACMG SF v3.0 list for reporting of secondary findings in clinical exome and genome sequencing: a policy statement of the American College of Medical Genetics and Genomics (ACMG)" by Miller et al, Genetics in Medicine, Vol:24, ISSN:1098-3600, Pages:744-746

Simoes Monteiro de Marvao A, McGurk K, Zheng S, et al.Simoes Monteiro de Marvao A, McGurk K, Zheng S, Thanaj M, Bai W, Duan J, Biffi C, Mazzarotto F, Statton B, Dawes T, Savioli N, Halliday B, Xu X, Buchan R, Baksi A, Quinlan M, Tokarczuk P, Tayal U, Francis C, Whiffin N, Theotokis A, Zhang X, Jang M, Berry A, Pantazis A, Barton P, Rueckert D, Prasad S, Walsh R, Ho C, Cook S, Ware J, O'Regan D close, 2021, Phenotypic expression and outcomes in individuals with rare genetic variants of hypertrophic cardiomyopathy, Journal of the American College of Cardiology, Vol:78, ISSN:0735-1097, Pages:1097-1110

Gudmundsson S, Karczewski KJ, Francioli LC, et al.Gudmundsson S, Karczewski KJ, Francioli LC, Tiao G, Cummings BB, Alfoldi J, Wang Q, Collins RL, Laricchia KM, Ganna A, Birnbaum DP, Gauthier LD, Brand H, Solomonson M, Watts NA, Rhodes D, Singer-Berk M, England EM, Seaby EG, Kosmicki JA, Walters RK, Tashman K, Farjoun Y, Banks E, Poterba T, Wang A, Seed C, Whiffin N, Chong JX, Samocha KE, Pierce-Hoffman E, Zappala Z, O'Donnell-Luria AH, Minikel EV, Weisburd B, Lek M, Ware JS, Vittal C, Armean IM, Bergelson L, Cibulskis K, Connolly KM, Covarrubias M, Donnelly S, Ferriera S, Gabriel S, Gentry J, Gupta N, Jeandet T, Kaplan D, Llanwarne C, Munshi R, Novod S, Petrillo N, Roazen D, Ruano-Rubio V, Saltzman A, Schleicher M, Soto J, Tibbetts K, Tolonen C, Wade G, Talkowski ME, Neale BM, Daly MJ, MacArthur DG close, 2021, The mutational constraint spectrum quantified from variation in 141,456 humans (vol 581, pg 434, 2020), Nature, Vol:597, ISSN:0028-0836, Pages:E3-E4

Tadros R, Francis C, Xu X, et al.Tadros R, Francis C, Xu X, Vermeer AMC, Harper AR, Huurman R, Bisabu KK, Walsh R, Hoorntje ET, te Rijdt WP, Buchan RJ, van Velzen HG, van Slegtenhorst MA, Vermeulen JM, Offerhaus JA, Bai W, de Marvao A, Lahrouchi N, Beekman L, Karper JC, Veldink JH, Kayvanpour E, Pantazis A, Baksi AJ, Whiffin N, Mazzarotto F, Sloane G, Suzuki H, Schneider-Luftman D, Elliott P, Richard P, Ader F, Villard E, Lichtner P, Meitinger T, Tanck MWT, van Tintelen JP, Thain A, McCarty D, Hegele RA, Roberts JD, Amyot J, Dube M-P, Cadrin-Tourigny J, Giraldeau G, L'Allier PL, Garceau P, Tardif J-C, Boekholdt SM, Lumbers RT, Asselbergs FW, Barton PJR, Cook SA, Prasad SK, O'Regan DP, van der Velden J, Verweij KJH, Talajic M, Lettre G, Pinto YM, Meder B, Charron P, de Boer RA, Christiaans I, Michels M, Wilde AAM, Watkins H, Matthews PM, Ware JS, Bezzina CR close, 2021, Shared genetic pathways contribute to risk of hypertrophic and dilated cardiomyopathies with opposite directions of effect, Nature Genetics, Vol:53, ISSN:1061-4036, Pages:128-+

Whiffin N, Karczewski KJ, Zhang X, et al.Whiffin N, Karczewski KJ, Zhang X, Chothani S, Smith MJ, Evans DG, Roberts AM, Quaife NM, Schafer S, Rackham O, Alföldi J, O'Donnell-Luria AH, Francioli LC, Genome Aggregation Database Production Team, Genome Aggregation Database Consortium, Cook SA, Barton PJR, MacArthur DG, Ware JS close, 2020, Characterising the loss-of-function impact of 5' untranslated region variants in 15,708 individuals, Nature Communications, Vol:11, ISSN:2041-1723, Pages:1-12

Mazzarotto F, Tayal U, Buchan RJ, et al.Mazzarotto F, Tayal U, Buchan RJ, Midwinter W, Wilk A, Whiffin N, Govind R, Mazaika E, de Marvao A, Dawes T, Felkin LE, Ahmad M, Theotokis PI, Edwards E, Ing AI, Thomson KL, Chan LLH, Sim D, Baksi AJ, Pantazis A, Roberts AM, Watkins H, Funke B, O'Regan D, Olivotto I, Barton PJR, Prasad SK, Cook SA, Ware JS, Walsh R close, 2020, Re-evaluating the genetic contribution of monogenic dilated cardiomyopathy, Circulation, Vol:141, ISSN:0009-7322, Pages:387-398

Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, et al.Garcia-Pavia P, Kim Y, Restrepo-Cordoba MA, Lunde IG, Wakimoto H, Smith AM, Toepfer CN, Getz K, Gorham J, Patel P, Ito K, Willcox JA, Arany Z, Li J, Owens AT, Govind R, Nuñez B, Mazaika E, Bayes-Genis A, Walsh R, Finkelman B, Lupon J, Whiffin N, Serrano I, Midwinter W, Wilk A, Bardaji A, Ingold N, Buchan R, Tayal U, Pascual-Figal DA, de Marvao A, Ahmad M, Garcia-Pinilla JM, Pantazis A, Dominguez F, John Baksi A, O'Regan DP, Rosen SD, Prasad SK, Lara-Pezzi E, Provencio M, Lyon AR, Alonso-Pulpon L, Cook SA, DePalma SR, Barton PJR, Aplenc R, Seidman JG, Ky B, Ware JS, Seidman CE close, 2019, Genetic variants associated with cancer therapy-induced cardiomyopathy, Circulation, Vol:140, ISSN:0009-7322, Pages:31-41

Walsh R, Mazzarotto F, Whiffin N, et al.Walsh R, Mazzarotto F, Whiffin N, Buchan R, Midwinter W, Wilk A, Li N, Felkin L, Ingold N, Govind R, Ahmad M, Mazaika E, Allouba M, Zhang X, de Marvao A, Day SM, Ashley E, Colan SD, Michels M, Pereira AC, Jacoby D, Ho CY, Thomson KL, Watkins H, Barton PJR, Olivotto I, Cook SA, Ware JS close, 2019, Quantitative approaches to variant classification increase the yield and precision of genetic testing in Mendelian diseases: The case of hypertrophic cardiomyopathy, Genome Medicine, Vol:11, ISSN:1756-994X

Halliday BP, Wassall R, Lota A, et al.Halliday BP, Wassall R, Lota A, Khalique Z, Gregson J, Newsome S, Jackson R, Rahneva T, Wage R, Smith G, Venneri L, Tayal U, Auger D, Midwinter W, Whiffin N, Rajani R, Dungu J, Cook S, Ware J, Baksi J, Pennell D, Rosen S, Cowie M, Cleland J, Prasad S close, 2019, Withdrawal of pharmacological treatment for heart failure in patients with recovered dilated cardiomyopathy (TRED-HF): an open-label, pilot, randomised trial, The Lancet, Vol:393, ISSN:0140-6736, Pages:61-73

Ware JS, Amor-Salamanca A, Tayal U, et al.Ware JS, Amor-Salamanca A, Tayal U, Govind R, Serrano I, Salazar-Mendiguchia J, Garcia-Pinilla JM, Pascual-Figal DA, Nunez J, Guzzo-Merello G, Gonzalez-Vioque E, Bardaji A, Manito N, Lopez-Garrido MA, Padron-Barthe L, Edwards E, Whiffin N, Walsh R, Buchan RJ, Midwinter W, Wilk A, Prasad S, Pantazis A, Baski J, O'Regan DP, Alsonso-Pulpon A, Cook SA, Lara-Pezzi E, Barton PJ, Garcia-Pavia P close, 2018, A genetic etiology for alcohol-induced cardiac toxicity, Journal of the American College of Cardiology, Vol:71, ISSN:0735-1097, Pages:2293-2302

Ware JS, Cook SA, 2017, Role of titin in cardiomyopathy: from DNA variants to patient stratification, Nature Reviews Cardiology, Vol:15, ISSN:1759-5002, Pages:241-252

Walsh R, Buchan R, Wilk A, et al.Walsh R, Buchan R, Wilk A, John S, Felkin L, Thomson KL, Chiaw TH, Chin Woon Loong C, Jian Pua C, Raphael C, Prasad S, Barton P, Funke B, Watkins H, Ware J, Cook SA close, 2017, Defining the genetic architecture of hypertrophic cardiomyopathy: re-evaluating the role of non-sarcomeric genes, European Heart Journal, Vol:38, ISSN:1522-9645, Pages:3461-3468

Alamo L, Ware JS, Pinto A, et al.Alamo L, Ware JS, Pinto A, Gillilan RE, Seidman JG, Seidman CE, Padron R close, 2017, Effects of myosin variants on interacting heads motif explain distinct hypertrophic and dilated cardiomyopathy phenotypes, Elife, Vol:6, ISSN:2050-084X

Whiffin N, Minikel E, Walsh R, et al.Whiffin N, Minikel E, Walsh R, O'Donnell-Luria A, Karczewski K, Ing AY, Barton PJR, Funke B, Cook SA, MacArthur DG, Ware JS close, 2017, Using high-resolution variant frequencies to empower clinical genome interpretation, Genetics in Medicine, Vol:19, ISSN:1530-0366, Pages:1151-1158

Schafer S, de Marvao A, Adami E, et al.Schafer S, de Marvao A, Adami E, Fiedler LR, Ng B, Khin E, Rackham O, van Heesch S, Pua CJ, Kui M, Walsh R, Tayal U, Prasad SK, Dawes TJW, Ko NSJ, Sim D, Chan LLH, Chin CWL, Mazzarotto F, Barton PJ, Kreuchwig F, de Kleijn DPV, Totman T, Biffi C, Tee N, Rueckert D, Schneider V, Faber A, Regitz-Zagrosek V, Seidman JG, Seidman CE, Linke WA, Kovalik J, O'Regan D, Ware JS, Hubner N, Cook SA close, 2017, Titin-truncating variants affect heart function in disease cohorts and the general population, Nature Genetics, Vol:49, ISSN:1546-1718, Pages:46-53

Lek M, Karczewski KJ, Minikel EV, et al.Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won HH, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG, Exome Aggregation Consortium close, 2016, Analysis of protein-coding genetic variation in 60,706 humans, Nature, Vol:536, ISSN:0028-0836, Pages:285-291

Walsh R, Thomson KL, Ware JS, et al.Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H close, 2016, Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples, Genetics in Medicine, Vol:19, ISSN:1530-0366, Pages:192-203

Ware JS, Li J, Mazaika E, et al.Ware JS, Li J, Mazaika E, Yasso C, DeSouza T, Cappola T, Tsai EJ, Hilfiker Kleiner D, Kamiya CA, Mazzarotto F, Cook SA, Halder I, Prasad SK, Pisarcik J, Hanley Yanez K, Alharethi R, Damp J, Hsich E, Elkayam U, Sheppard R, Kealey A, Alexis J, Ramani G, Safirstein J, Boehmer J, Pauly DF, Wittstein IS, Thohan V, Zucker MJ, Liu P, Gorcsan J, McNamara DM, Seidman CE, Seidman JG, Arany Z close, 2016, Shared genetic etiology of peripartum and dilated cardiomyopathies, New England Journal of Medicine, Vol:374, ISSN:1533-4406, Pages:233-241

Homsy J, Zaidi S, Shen Y, et al.Homsy J, Zaidi S, Shen Y, Ware JS, Samocha KE, Wakimoto H, Gorham J, Chih Jin S, Deanfield J, Giardini A, Porter Jr. GA, Kim R, Bilguvar K, Lopez F, Tikhonova I, Mane S, Romano Adesman A, Qi H, Vardarajan B, Ma L, Daly M, Roberts AE, Russell MW, Mital S, Newburger JW, Gaynor JW, Breitbart RE, Iossifov I, Ronemus M, Sanders SJ, Kaltman JR, Seidman JG, Brueckner M, Gelb BD, Goldmuntz E, Lifton RP, Seidman CE, Chung WK close, 2015, De novo mutations in congenital heart disease with neurodevelopmental and other birth defects, Science, Vol:350, ISSN:0036-8075, Pages:1262-1266

Roberts AM, Ware JS, Herman DS, et al.Roberts AM, Ware JS, Herman DS, Schafer S, Baksi J, Bick AG, Buchan RJ, Walsh R, John S, Wilkinson S, Mazzarotto F, Felkin LE, Gong S, L MacArthur JA, Cunningham F, Flannick J, Gabriel SB, Altshuler DM, Macdonald PS, Heinig M, Keogh AM, Hayward CS, Banner NR, Pennell DJ, O'Regan DP, San TR, de Marvao A, W Dawes TJ, Gulati A, Birks EJ, Yacoub MH, Radke M, Gotthardt M, Wilson JG, O'Donnell CJ, Prasad SK, Barton PJ, Fatkin D, Hubner N, Seidman JG, Seidman CE, Cook SA close, 2015, Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease, Science Translational Medicine, Vol:7, ISSN:1946-6234, Pages:270ra6-270ra6

McDermott-Roe C, Ye J, Ahmed R, et al.McDermott-Roe C, Ye J, Ahmed R, Sun XM, Serafin A, Ware J, Bottolo L, Mucket P, Canas X, Zhang J, Rowe GC, Buchan R, Lu H, Braithwaite A, Mancici M, Hauton D, Marti R, García-Arumí E, Hubner N, Jacob H, Serikawa T, Zidek P, Papousek F, Kolar F, Cardona M, Ruiz-Meana M, García-Dorado D, Comella JX, Felkin LE, Barton PJ, Arany Z, Pravenec M, Sanchis D, Cook SA close, 2011, Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function, Nature, Vol:478, Pages:114-118

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