Meet the team
Pantazis TheotokisBioinformatician | Data Manager
If you're interested in joining the LMS
“What are the genetic causes of cardiomyopathy?”
We are working to understand more about the causes of cardiomyopathy – disorders that affect the muscles of the heart.
Cardiomyopathy reduces the ability for the heart to effectively pump blood around the body, and can lead to an irregular heartbeat, with symptoms worsening over time.
Cardiomyopathy conditions can be genetic or environmental, with some caused by viral infections, lifestyle choices or some inherited from parents.
We are interested in the Titan gene, which encodes the largest human protein and a key component of human muscle. It has been identified as the most important cause of inherited cardiomyopathy.
Through our work, we aim to determine gene networks and define biological pathways to help uncover new mechanisms, diagnostics and therapeutic targets for cardiomyopathy.
We analyse and combine large data sets from patients, trials and wider research to help identify new patterns.
We employ a range of approaches including sequencing genomic data, utilising studying medical imagery, RNA sequencing and evaluating electronic health records to make new insights into human cardiovascular disease.
Cardiomyopathy can vary in severity. It can lead to heart failure and result in death, regardless of age or health. We hope our findings will provide diagnostic answers to affected families and help identify new therapeutic targets.
“We aim to understand the genetic basis of cardiovascular disease in order to both reveal disease mechanisms, thereby identifying new therapeutic targets, and to interpret genomic information for application in patient care.”
We are using genetic and 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.
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.
Central to our work is the integration of genome data with cutting-edge phenotypic characterisation. We leverage cardiac magnetic resonance (CMR) imaging, machine-based image processing and quantitative multi-dimensional feature extraction techniques, transciptomics and translatomics, and other large data sets including electronic health records, to make new insights into human cardiovascular disease.
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.
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.
These studies are complemented by RNA sequencing of the human heart and protein-protein interactomes that enable us to build gene networks and define biological pathways, with the aim of uncovering novel mechanisms, diagnostics and therapeutic targets.
Web resources, software, and other tools developed by the group are available at cvgenetics.org/resources.
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