The Edinburgh Cancer Discovery Unit (ECDU) was founded in 2011 as a not-for-profit organization to provide a multidisciplinary group of core skills embracing advanced technology platforms and disease models which drive innovations in oncology drug discovery and development.
The overarching aims of the ECDU are to: Enhance clinical predictivity of preclinical oncology discovery strategies by applying an evidence-led translational research platform, incorporating disease relevant models systems, state-of-the-art quantitative preclinical imaging and genomic/proteomic discovery technologies. When applied together these approaches provide unique insights into compound and target mode-of-action in complex biological systems enabling more informed target validation, lead optimization, candidate drug selection and clinical trial designs.
The overarching aims of the ECDU are to: Enhance clinical predictivity of preclinical oncology discovery strategies by applying an evidence-led translational research platform, incorporating disease relevant models systems, state-of-the-art quantitative preclinical imaging and genomic/proteomic discovery technologies. When applied together these approaches provide unique insights into compound and target mode-of-action in complex biological systems enabling more informed target validation, lead optimization, candidate drug selection and clinical trial designs.
Our Capabilities:
- interaction proteomics/mass spectrometry (and associated bio-informatics) of preclinical and clinical samples (B Serrels, V Brunton and M Frame).
- high-content imaging. Olympus Scan R and IncuCyte kinetic imaging platforms incorporating; primary patient derived cells, 3D models and multiparametric phenotypic profiling applications.
- quantitative high resolution in vivo cancer imaging methodology -Optical window technology and probe building – rapid and quantitative interrogation of cancer biology mechanisms and tumour response phenotypes in vivo. Includes direct administration of early phase compound to live in vivo tumour to confirm in vivo activity prior to further development.
- imaging interactions within the complex tumour/host microenvironment -in vivo transgenic reporter mice.
- multi-modal CARS/2-photon label-free cancer and ‘drug’ imaging -coupling Raman spectroscopy with second harmonic generation tissue signals (collaboration between A Serrels, A Elfick and A Downes) . Precise quantification of intra tumour pharmacokinetics. Monitoring drug uptake and retention to guide optimal in vivo scheduling and drug combination strategies.
- pharmacodynamic pathway modelling– ultra-sensitive reverse phase protein microarrays (Nitrocellulose and Zeptosens platforms). Applied to informative models of drug sensitivity and/or clinical samples to inform on how to collapse pathway network robustness; confirming drug mode-of-action and identifying and prioritizing rational combination sets and putative biomarker strategies.
- predictive combination screening in genetically engineered models of cancer (complex genetic mice) and bespoke in vitro high content assays -incorporating 3D models, organotypic co-culture systems and patient derived primary cells (in associated with protein array analysis).
These technologies and methodologies can stand alone in a wide range of research applications. However, their integration within the Edinburgh Cancer Discovery Unit (ECDU) in the Institute of Genetics and Molecular Medicine (IGMM) at the Western General Hospital Campus, including close interaction with clinicians and the local clinical trials unit, provides an optimal setting to combine their application to advance translational cancer drug discovery and development.
Our Team:
The ECDU is located within the Edinburgh Cancer Research UK Centre which forms part of the Institute of Genetics and Molecular Medicine (IGMM) within the University of Edinburgh. The ECDU is jointly directed by three scientists that bring together complimentary skills and experience in basic cancer research, pharmacology, drug discovery and imaging gained from within academic and industry environments.:
Prof Margaret Frame PhD FRSE, Science Director Edinburgh Cancer Research Centre
KOL tumour invasion, metastasis and adhesion network biology.
Dr Val Brunton: Principal Investigator Cancer Pharmacology
in vivo modelling and intravital imaging. Extensive experience in leading academic-industry collaborations. Lead scientist on Coherence Anti-Stokes Raman Spectroscopy (CARS) imaging .
Dr Neil Carragher: Principal Investigator Drug discovery
High-content screening, and rational drug combination/ biomarker strategies. 9.5 years pharmaceutical industry experience including 6 years at AstraZeneca (Principal Scientist) where responsible for bespoke assay development, project delivery, and several global strategic initiatives.
Prof Margaret Frame PhD FRSE, Science Director Edinburgh Cancer Research Centre
KOL tumour invasion, metastasis and adhesion network biology.
Dr Val Brunton: Principal Investigator Cancer Pharmacology
in vivo modelling and intravital imaging. Extensive experience in leading academic-industry collaborations. Lead scientist on Coherence Anti-Stokes Raman Spectroscopy (CARS) imaging .
Dr Neil Carragher: Principal Investigator Drug discovery
High-content screening, and rational drug combination/ biomarker strategies. 9.5 years pharmaceutical industry experience including 6 years at AstraZeneca (Principal Scientist) where responsible for bespoke assay development, project delivery, and several global strategic initiatives.
Selected Publications:
- Carragher N. 2011. Advancing high content analysis towards improving clinical efficacy. European Pharmaceutical Review. 16(1): 12-16.
- Isherwood B, Timpson P, McGhee EJ, Anderson KI, Brunton VG, Canel M, Serrels A and Carragher NO. 2011. Live cell in vitro and in vivo imaging applications: Accelerating Drug Discovery. Pharmaceutics. 3(2), 141-170.
- Storr SJ, Carragher NO, Frame MC, Parr T, Martin SG. 2011. The calpain system and cancer. Nature Reviews Cancer. May;11(5):364-74.
- McGhee EJ, Morton JP, Von Kriegsheim A, Schwarz JP, Karim SA, Carragher NO, Sansom OJ, Anderson KI, Timpson P. 2011. FLIM-FRET imaging in vivo reveals 3D-environment spatially regulates RhoGTPase activity during cancer cell invasion. Small Gtpases. 2011 Jul;2(4):239-244
- Carragher NO. and Frame MC. 2011. Modelling distinct modes of tumour invasion and metastasis. Drug Discovery Today: Disease Models. Aug:2-3(8): 103-112.
- Carragher NO, Unciti-Broceta A, Cameron D. 2012. Advancing cancer drug discovery towards more agile development of targeted combination therapies. Future Medicinal Chemistry. Jan;4(1):87-105.
- Carragher, NO Brunton VG, Frame MC. 2012 Combining Imaging and Pathway Profiling: An Alternative Approach to Cancer Drug Discovery. Drug Discovery Today. March; 17 5-6: 203-214.