James Ware is a Clinical Senior Lecturer in Genomic Medicine at Imperial College London and Honorary Consultant Cardiologist at Royal Brompton and Harefield Hospitals. His research group spans the National Heart & Lung Institute, the Royal Brompton Cardiovascular Biomedical Research Unit, and the MRC Clinical Sciences Centre, and is supported by an Intermediate Clinical Fellowship from the Wellcome Trust.
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.
Gene discovery in rare cardiovascular disease – we are using exome and genome sequencing approaches to find genes that cause rare Mendelian disease, particularly severe childhood cardiomyopathies (heart muscle diseases), both to provide answers to the families affected, and also to find new therapeutic targets for the treatment of these conditions.
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 genetics and 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.
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.
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, 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.
et al., 2016, Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples., Genet Med
et al., 2016, Analysis of protein-coding genetic variation in 60,706 humans, Nature, Vol:536, ISSN:0028-0836, Pages:285-+
et al., 2016, Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies, New England Journal of Medicine, Vol:374, ISSN:0028-4793, Pages:233-241
et al., 2015, De novo mutations in congenital heart disease with neurodevelopmental and other congenital anomalies, Science, Vol:350, ISSN:0036-8075, Pages:1262-1266
et al., 2015, Interpreting de novo Variation in Human Disease Using denovolyzeR., Curr Protoc Hum Genet, Vol:87, ISSN:1934-8266, Pages:7.25.1-7.2515
et al., 2015, Bayesian models for syndrome- and gene-specific probabilities of novel variant pathogenicity, Genome Medicine, Vol:7, ISSN:1756-994X
et al., 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
et al., 2013, Paralogue annotation identifies novel pathogenic variants in patients with Brugada syndrome and catecholaminergic polymorphic ventricular tachycardia, Journal of Medical Genetics, Vol:51, ISSN:1468-6244, Pages:35-44
et al., 2011, Endonuclease G is a novel determinant of cardiac hypertrophy and mitochondrial function, Nature, Vol:478, ISSN:0028-0836, Pages:114-118