Ian Overton

Dr

  • Room 0G.064 - H.S.B

    United Kingdom

Accepting PhD Students

20012020

Research output per year

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Personal profile

Research Interests

We work to understand how cancer cells can spread around the body (metastasis) and how they become resistant to treatment with drugs; these factors cause the overwhelming majority of cancer deaths. We also develop software to make sense of increasingly large datasets and to inform clinical decision-making, for example to predict which patients will respond to a particular treatment. Together, these approaches help to develop better and more effective cancer medicine.
Cells are organised and controlled by complex interactions between many individual parts (molecules), and so inherently form intricate networks. The properties of these networks underlie virtually every aspect of cell function. We map and analyse the messages passed, or information flow, amongst molecules by integrating billions of data points that describe key components such as DNA and proteins. Statistical inference, including machine learning, lets the data do the talking in order to reveal the molecular logic that controls health and disease. Indeed, computers are vital to modern biology, which interprets large datasets to gain insight into complex systems.

Main research areas:
1. Understanding molecular control and consequences of cell phenotypic plasticity in metastasis and drug resistance.
2. Developing more effective approaches for cancer patient stratification.
3. Generation of novel algorithms, techniques and computational workflows to advance the above.

Here's a short video about my research interests.

Research Statement

Navigating from molecular measurements to phenotype implies understanding gene function (including gene products and their products). Many genes are poorly characterised, but coordinately regulated, for example in differentiation, and new functions continue to be discovered even for deeply studied coding genes. Most noncoding genes (e.g. lncRNA, miRNA) are not well understood, nor isoforms arising from alternate splicing. Thus, a substantial portion of gene function is uncharted. Data driven networks provide useful abstractions to fill these knowledge gaps, enabling testing and generation of mechanistic hypotheses. One example current application in the group is the design of combination therapies to overcome drug resistance.

The spread of cells from a primary tumour to a secondary site remains one of the most life-threatening pathological events. Epithelial-Mesenchymal Transition (EMT) is a cell programme involving loss of cell-cell adhesion, gain of motility, invasiveness and survival; these properties are fundamental for metastasis. Epithelial remodelling is also crucial for development. Reactivation of a programme resembling EMT is a credible mechanism for key aspects of the invasion-metastasis cascade and an MET-like process may produce the differentiation frequently observed in secondary tumours. Indeed, oncofetal signalling pathways (e.g. Hedgehog, Wnt, TGF-beta) activate EMT, and promote metastasis in multiple cancers.

We have generated probabilistic systems-wide gene networks and are using these to investigate aspects of EMT/MET in different contexts; including to identify new EMT players, pathway crosstalk and drivers of metastasis. We also infer small scale causal networks combining ex vivo immunohistochemical and clinical measurements. These models integrate carefully selected data to represent the specific biological/clinical context of interest, including multiple 'omics datasets. Therefore, our work involves integration of 'big data' with machine learning and graph theoretic/statistical analyses. A wide range of techniques are employed, including supervised and unsupervised learning as well as information-theoretic approaches such as conditional mutual information. Performance is assessed by rigorous benchmarking with blind test data.

Novel algorithms are developed where required to advance biomedical understanding, for example we are working on methods towards systems-wide dynamic modelling of drug response in renal and prostate cancers. Tools developed in the group are made widely accessible (e.g. TMA Navigator). We collaborate closely with clinical colleagues and aim to translate results into medical practise.

Achievements

University of Edinburgh Chancellor's Fellowship (2015)

Member of the Royal Society of Edinburgh Young Academy of Scotland (2011)

Scottish Crucible Fellow (2010)

Royal Society of Edinburgh Scottish Government Fellowship (2009)

 

Other

Websites:
Royal Society of Edinburgh Young Academy of Scotland Open Data working group - https://www.youngacademyofscotland.org.uk/our-work/smarter/

TMA Navigator: network inference, patient stratification and survival analysis with tissue microarray data - www.tmanavigator.org

Teaching

Coordination and assessment for modules 'Dissertation Research Project' and 'Systems Medicine: From Molecules to Populations' within the Bioinformatics and Computational Genomics MSc. Lecturing to students from the following MSc courses: i) Bioinformatics and Computational Genomics, ii) Molecular Pathology of Cancer, iii) Cancer Medicine & Oncology Drug Discovery. Supervision of Postgraduate and Undergraduate Dissertation research projects and internships. Tutor for Medical Undergraduate Personal & Professional Development Portfolio.

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