NIHR Barts Biomedical Research Centre award (2022-2027)

We host three Cancer Research UK Centres and led experimental medicine that established 400 NHS fresh tissue pathways and generated high fidelity tumour genomes on >17,000 patients. Barts led the development of novel cancer therapies in triple negative breast, and urothelial malignancy leading to international adoption.

We are extending this multi-omic approach to provide precision medicine to address unmet need in breast, pancreatic, urothelial, gastrointestinal and haematological malignancies.

We are combining this with our world-leading translational research into personalised therapies and biomarkers of response to transform patient care.

We are working with industry partners and the Experimental Cancer Medicine Centres (ECMC) network and the BRC network to support stratified cancer trials and create a national agnostic platform to evaluate and optimise cell-free DNA utility.

We are integrating novel approaches to clinical trials with deep patient characterisation novel multi-omic approaches and creating an innovative liquid biopsy analysis platform to address key clinical challenges for maximum impact.

We have three research questions to answer:

1. Can molecular signatures drive discovery and precision interventional clinical trials to improve outcomes?
2. Can integrated risk scores combined with liquid biopsy biomarkers achieve earlier diagnosis for pancreatic cancer and early-stage lesions in breast cancer?
3. Can deep phenotyping combining multi-omic signatures and healthcare data identify patients most at risk of cancer recurrence?

Co-Theme Leads:

Professor Thomas Powles and Professor Louise Jones

Key Clinicians and Researchers:

Precision clinical trials and therapy: Professor Marco Gerlinger; Professor John Gribben; Professor Hemant Kocher; Professor Tom Powles; Professor Peter Schmid

Precision diagnostics and Biomarker discovery: Professor Tatjana Crnogorac-Jurcevic; Professor Kairbaan Hodivala-Dilke; Professor Louise Jones; Professor Nicholas Lemoine; Professor John Marshall; Dr Jessica Okusun

Bioinformatics, healthcare science & data modelling: Professor Claude Chelala

The Precision Genomic Medicine theme capitalises on Europe’s largest heart hospital, the Barts Heart Centre (~85,000 episodes/year).

We a driving forward a pan-rare disease re-analysis of 100KGP families harnessing this infrastructure to undertake advanced genomic analyses, AI, multi-omics and functional genomics to solve really challenging rare heart rhythm disorders where we have created national platforms and the current diagnostic yield is 7.5%.

By combining the strengths and patients at Barts and St George’s Hospitals including the St George’s Inherited Cardiac Conditions and Sudden Death Biobank, we are transforming diagnostic yield in rare heart rhythm disorders and unexplained sudden death and evaluating the role of inflammation. This benefits from BRC integrated platforms combining digital pathology (cardiovascular, musculoskeletal and cancer), whole genome sequences with single cell multi-omics to enable family screening to avoid death.

Furthermore, combining our unique patient and population resources, we are tackling cardiovascular disease (CVD) by improving patient care and promoting disease prevention in diverse communities. In addition, we are defining a comprehensive repertoire of somatic adrenal mutations driving hypertension and evaluate novel therapeutic strategies.

We have four research questions upon which we will answer utilising our strengths within this theme. These are:

1. Can integrated deep phenotyping with multi-omics and advanced analytics make a step change in diagnosis of arrhythmias and inflammatory cardiomyopathies?
2. Can polygenic risk scores (PRS) be optimised for improving CVD patient care and disease prevention in diverse communities?
3. Can somatic mutations in primary aldosteronism (PA) guide patient stratification and novel therapies?
4. Can CVD molecular signatures drive discovery and precision therapy, maximising benefit: risk for patients under-represented in conventional trials?

Co-Theme Leads: 

Professor Panos Deloukas and Professor Patricia Munroe

Key Clinicians and Researchers:

Professor Michael Barnes; Professor Elijah Behr; Professor Morris Brown; Professor Sir Mark Caulfield; Professor Panos Deloukas; Professor Pier Lambiase; Professor Federica Marelli-Berg; Professor Anthony Mathur; Professor Patricia Munroe; Professor Mauro Perretti; Professor Steffen Petersen; Professor Mary Sheppard; Professor Damien Smedley; Professor Andrew Tinker; Professor David van Heel

The digital era has heralded an exponential growth in sensing technologies and data acquisition. This Theme is harnessing this wealth of information to improve healthcare delivery and patient outcomes for cardiovascular conditions of particularly high burden in the East End of London.

We are using the cardiovascular digital twin concept to digitally model three disease states where we already innovate in drug and/or device development: acute coronary syndromes, valvular heart disease and hypertension.

These models are created by inputting data from available existing and novel wearables, sensing technologies, apps and large data registries. Using this data, we are creating digital models with novel algorithms developed by our team to provide personalised patient treatment plans, supporting their disease management, predicting disease states/trends and enabling device choice/design by predicting the patient’s response.
These models will improve patient symptoms and long-term outcomes and better utilise NHS resource.

These digital models also support innovative clinical trials of cardiovascular devices and therapies for these diseases (e.g., patient selection/enrolment criteria by predicting patient response) – ultimately decreasing recruitment numbers needed and risks to the participant.

These technologies also enable real-time patient follow-up by increasing accuracy and reliability and decreasing time and costs. All patients recruited are included in the Barts CVCTU Interventional Trial Database Resource to input into digital models and establish a new cardiovascular trial resource for further studies.

We are using this approach to address the following four research questions:

1. Can we comprehensively represent each patient’s cardiovascular anatomy, physiology and pathophysiology from sensing and imaging technologies?
2. Can we use individualised data to create bespoke treatments and novel devices?
3. Can we prototype and test these solutions in a unique simulated environment?
4. Can we validate solutions though trials utilising digital technologies, and can these technologies be adapted to musculoskeletal and cancer?

Co-Theme Leads:

Professor Anthony Mathur and Professor Amrita Ahluwalia

Key Clinicians and Researchers:

Professor Amrita Ahluwalia; Professor Michael Barnes; Professor Andreas Baumbach; Dr Ajay Gupta; Professor Adrian Ionescu; Dr Dan Jones; Dr Vikas Kapil; Professor Rich Kerswell; Professor Rob Krams; Professor Anthony Mathur; Professor Steffen Petersen; Dr Krishnaraj Rathod; Dr Caroline Roney; Dr Manish Saxena; Professor Greg Slabaugh

Musculoskeletal (MSK) conditions affect over 14.9m people nationally, represent 20% of GP consultations and are the second biggest cause of sickness absence, costing the UK economy £7bn per year and £5bn per year directly to the NHS. 

While biologic therapies have revolutionised management of rheumatoid arthritis, huge clinical challenges remain with 40% of patients reporting a poor therapeutic response, 10-20% remain refractory to all current medications leading to delayed disease control and disability. No biologics are currently available for Sjorgrens syndrome, while in osteoarthritis absence of disease-modifying therapy leads to >250,000 NHS prosthetic replacements per year. 

Building off our first worldwide biopsy-driven, randomised-clinical trials and unique biomedical resource linking histological/molecular pathotypes to clinical and treatment response phenotypes; our multidisciplinary research team will apply multi-modality data integration to high burden, common MSK diseases to address major areas of unmet need.

Precision Musculoskeletal Care pioneered the selection of biologics tailored to patients’ synovial pathotype (Lancet 2021). We will combine deeper phenotyping and remote patient disease activity monitoring (see Precision Digital Health, Cardiovascular Devices and Trials), with pan-BRC digital pathology (with Cardiovascular and Cancer) and single cell multi-omic profiling, including a novel method of immune repertoire sequencing across a suite of funded trials with Manchester (joint MRC funding), Oxford (joint Versus Arthritis Osteoarthritis Centre), Bristol & Nottingham (Perioperative Care TRC).

Through deep clinical, biomechanical, molecular and imaging phenotyping we will drive AI analyses generating novel predictive algorithms to answer the research questions of: 

1. Who will rapidly progress and when? (precision detection/surveillance).
2. Which cellular, molecular, bio-mechanical mechanisms/pathways underpin disease progression/treatment resistance for novel target identification? (precision pathogenesis/discovery). 
3. Who will respond/non-respond to current/novel medications? (precision stratification/therapy). 

Co-Theme Leads:

Professor Costantino Pitzalis and Professor Xavier Griffin

Key Clinicians and Researchers:

Personalised healthcare, multi-omics & Clinical Trials: Professor Michele Bombardieri; Professor Jack Cuzik; Professor Rhian Gabe; Professor Xavier Griffin; Dr Myles Lewis; Professor Dylan Morrissey; Professor Costantino Pitzalis

Novel Therapeutics & Target Discovery: Professor Francesco Dell’Accio; Dr Karin Hing; Professor Mauro Perretti; Professor Gleb Sukhorukov 

In-vitro Testing/Organ-chip Models/Tissue-Engineering/Biomechanical-Imaging-Pain phenotyping: Professor Michael Barnes; Professor Norman Fenton; Professor Shaogang Gong; Professor Himadri Gupta; Professor Martin Knight; Professor David Lee; Professor Hazel Screen; Dr Shafaq Sikandar; Professor Greg Slabaugh