Understanding disease biology with the Smart Trials Hub

The Smart Trials Hub will use the latest technology to advance our understanding of personalised disease biology.

Dr Anatoliy Markiv, from the King’s Health Partners Rare Disease Network, speaks to Prof Maddy Parsons, Professor of Cell Biology at King’s College London, and Steven Lynham, Smart Trials Hub Facility Manager, to find out more.

What is the Smart Trials Hub?

The King’s College London Smart Trials Hub is an exciting new facility being built at Guy’s Hospital campus, applying advanced multi-modal technology to understand disease biology in granular detail to enable equitable development of personalised therapies. It will house state-of-the-art spatial and non-spatial ‘omics technologies to enable full molecular profiling of cells, tissues and liquid biopsies.

Technologies span transcriptome, proteome, metabolome, chemical/elemental and non-cellular features in context. The hub will also enable researchers to use patient-derived organoids and ex-vivo live tissues to test emerging mechanisms created from matched patient samples.

Why was the hub created?

The revolution in spatial biology technologies and AI-driven data interpretation means we can now create a full picture of human tissues to gain unprecedented mechanistic insight into disease biology. The Smart Trials Hub aims to use these technologies to understand why some patients respond to existing therapies and others do not, and to decode the spatial molecular make-up of tissues to identify new targets for treatments.

What challenge does the hub address?

Most current clinical trials do not represent the patient population they aim to serve and often fail because the diversity in disease mechanisms is poorly understood. The Smart Trials Hub aims to address this challenge by 1) providing a comprehensive understanding of the underpinning biology in hard-to-treat disease, and 2) determining why some patients respond to current treatments and others do not - and how population level diversity contributes to this.

How does the hub study patient responses?

By using the combined power of spatially encoded high-dimensional signatures in patient samples and in vitro ‘digital twins’, the Smart Trials Hub will help to define molecular features that correspond with an individual’s response to therapy, and where this deviates in those who do not respond. Identified targets for intervention can then be tested on companion in vitro models of human disease with the goal of identifying ways to treat everyone effectively.

What role does artificial intelligence play?

Thousands of data points are created through the combined multimodal omics approaches and these are not possible to interpret without the use of advanced computational techniques. This includes machine learning/AI models that draw diverse types of molecular data together to create patterns to predict therapy response and highlight new targets for intervention.

How can rare disease patients benefit?

The hub will accelerate ongoing initiatives to understand why rare disease patients – who often carry the same underlying genetic variants - do not all respond to existing therapies. Adopting a comprehensive approach to understanding the biology in the specific disease and affected tissue(s) will reveal previously hidden drug-resistant features and targetable pathways.

This is an exciting opportunity to harness the broader understanding of diverse disease features that the hub will create and apply these learnings to identify rare disease patients who may benefit immediately from existing, approved therapies.

Who are the hub’s collaborators?

The hub is an open access facility and supports the entire biomedical research community and our NHS Trust partners. Several globally leading pharmaceutical companies are already partnering with the hub to harness the technology to develop better therapies and design more targeted clinical trials. We also work closely with the technology providers to share knowledge and ensure our platforms are at the forefront of the field, enabling greater discoveries in disease biology.

How can King’s College London researchers get involved?

The hub is open to any researchers at the university, and we really encourage anyone who is interested in undertaking these types of advanced profiling approaches to get in touch at smarttrialshub@kcl.ac.uk to discuss their project. We are also talking to lots of researchers in our health faculties – and to other external partners – to ensure the capabilities and potential benefits of working with the hub are spread as far and wide as possible!

What resources can collaborators access?

The hub will operate largely as a service facility; users discuss their project with the team, design the experiments and analysis approaches, and the profiling is then carried out by the facility. Researchers will be engaged at every step of the process with opportunities to learn, share knowledge and build a collective understanding of complex human disease.

What’s the ultimate goal?

Ultimately, the Smart Trials Hub aims to accelerate insight into human disease and identify ways to treat those patients who currently have no therapeutic options. In doing so, the hub will support development of ‘Smart’ clinical trials that are grounded in the underpinning biology leading to more successful, targeted drugs to treat individuals’ disease.  

The King’s Health Partners Rare Disease Network seeks to unite our clinical and research communities with the shared vision of delivering better health outcomes and improving the lives of those affected by rare diseases. To learn more, visit its webpage here.

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