Target Discovery and Functional Validation

The target discovery and functional validation programme led by Dr Rebecca Harris, focuses on 1) the characterisation and optimisation of complex cellular or patient-derived disease models, and 2) their application to identify clinically relevant, high confidence targets for disease therapy. The team combine academic discovery with industry rigour, defining end-goal criteria and building go/ no go decision making points into all projects. The team works in collaboration with academics and clinicians in Cambridge who have expertise in specific disease areas and have developed biologically relevant cell-based models. By considering how these models could be applied to drug discovery workflows they further refine the models and generate screening outputs to deliver a pipeline of novel targets. Many projects involve an exchange with the Computational Research team to interpret and interrogate datasets and they integrate AI and machine learning methodology into their target discovery approach.

 


Dr Rebecca Harris

CRUK CAMBRIDGE CENTRE
From 2017-2022 the Milner Therapeutics Institute delivered the Onco-Innovation programme, one of 12 original foundation programmes within the CRUK Cambridge Centre. The programme was managed by Dr Rebecca Harris, and led by our director Tony Kouzarides, alongside Susan Galbraith (AstraZeneca). A key objective was to establish the Milner as a physical institute, which was accomplished when the JCBC opened in 2019. From 2022, the MTI has been elevated to an affiliated institute within the CRUK CC structure, and we look forward to continuing our close interactions across the whole Centre, working to support entrepreneurship, enable pre-clinical industry-academic collaboration and to integrate clinical engagement early in oncology target discovery research within the MTI.

Discover our Research:

Team Members

Dr Rebecca Harris
Head of Target Discovery

Rex
Li
Research Associate

Thomas Dennison
Research Associate

 

SukJun
Lee
 
Research Associate 

Team Members

Dr Rebecca Harris
Head of Target Discovery

Rex Li
Research Associate

SukJun Lee 
Research Associate 

Thomas Dennison
Research Associate

Research Collaborations

Matthias Zilbauer 
Wellcome-MRC Cambridge Stem Cell Institute

Frank McCaughan
CRUK Cambridge Centre

 

Research Collaborations: Case Studies

Case Study: Matthias Zilbauer, Inflammatory Bowel Disease

Profiling of human gut models for identification and validation of novel targets for IBD

  • Characterisation of patient-derived mucosal organoids and iPSC derived organoids +/- inflammatory stimuli
  • Healthy vs disease, multiple gut segments
  • Extensive disease model optimisation
  • Functional assay development
  • Integration of computational research to identify key pathways/targets

 

Case Study: Frank McCaughan, Lung Cancer

Identification of novel epigenetic and co-transcriptional drivers of squamous lung cancer

  • Integrational of computational and experimental approaches
  • AI approaches have been used to identify new potential drugs to treat squamous lung cancer
  • Small molecules being tested in cell lines and the lung organotypic model
  • CRISPR approaches to disrupt novel targets also being deployed
  • Phenotypic and mechanistic studies

Research

– Disease signature identification and target validation through the
Centre for Pathway Analysis

– Integration of clinical engagement early in discovery research through the CRUK Cambridge Centre

Industry Engagement and Collaboration

– Facilitate pre-clinical industry-academic collaboration across the CRUK Cambridge Centre

– Leverage industry network of the Milner Consortium

10 pre-clinical projects established within the CRUK Cambridge Centre (view projects)

Entrepreneurship and Training

– The MTI is home to accelerator
Start Codon with a number of oncology-focused start-ups

– Oncology companies based within the MTI benefit from facilities & collaborative environment

– We promote training & entrepreneurship through events such as TGIO

An organoid in the sigmoid colon, a section of the large intestine. The green colour is a stem marker called LGR5, the red is a cell membrane marker called e-cadherin, and the blue is a nuclei stain called DAPI. Video by April Foster.
An organoid in the terminal ileum, a section of the small intestine. The green colour is a stem marker called LGR5, the red a cell membrane marker called e-cadherin, and the blue is a nuclei stain called DAPI. Video by April Foster.