Dr Adrian Biddle

Profile

I obtained my BSc in 2003 from the University of Bristol. I then spent a year working on cancer therapeutics at Dartmouth College, New Hampshire, before studying for a PhD on the topic of nuclear reprogramming under the supervision of Professor John Gurdon at Cambridge University. I obtained my PhD in 2008 and began postdoctoral work on cancer stem cells with Professor Ian Mackenzie at Queen Mary, University of London. In 2012, I obtained an NC3Rs David Sainsbury fellowship that enabled me to establish an independent research program around the theme of cancer stem cell heterogeneity and plasticity in cancer. As part of this fellowship, I spent three months working with Dr John Stingl at the Cancer Research UK Cambridge Institute. I was included in the Queen Mary, University of London submission to REF2014.

In 2016, I was appointed to the DHT lectureship in animal replacement science within the Blizard Institute

 

Website: https://sites.google.com/view/biddlelab-qmul/home 

 

Summary

Dr Biddle is a DHT lecturer in animal replacement science within the Centre for Cell Biology and Cutaneous Research

Dr Biddle is an NC3Rs Research Fellow in the Centre for Cell Biology and Cutaneous Research. His research interest is in non-genetic cellular heterogeneity in cancer, and how such heterogeneity might be responsible for therapeutic resistance. He is particularly interested in the plasticity of heterogeneous cancer cell sub-populations, the molecular mechanisms driving plasticity, and how plastic sub-populations can be modelled in vitro.

Dr Biddle organises the London in vitro cancer and stem cell models club. If you are interested in joining the club mailing list, please send Dr Biddle an e-mail.

Teaching

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Research

Research Interests:

Lay summary: Cancer remains a serious life-threatening condition and the therapies currently available are not always able to prevent its recurrence or spread. Recent work suggests that only a small fraction of the total cancer cells, the cancer stem cells, are responsible for the growth of cancers. Tumour recurrence may result from the ability of these cells to resist being killed. We have shown that cancer stem cells can switch between two different identities, one that drives tumour growth and another that drives metastatic spread. However, only some cancer stem cells within a tumour possess this special ability to switch identity, and these cells are particularly dangerous as they can drive the important processes of growth and metastasis that underlie cancer progression. We aim to demonstrate that human cells in a dish can form an effective model for the development of drugs that target these cells.

Scientific summary: We explore the novel concept that heterogeneous cancer stem cell phenotypes exist within individual tumours, and investigate the underlying cellular plasticity that drives this heterogeneity. This has the potential to help explain the wide variation in progression and therapeutic response seen between different tumours, by relating this variation to the presence of different cancer stem cell phenotypes created by re-activation of latent developmental plasticity. By seeking to identify the molecular events underlying this plasticity, our research has the potential to uncover novel avenues for therapeutic intervention in cancer. More generally, it is hoped that it will help to further our understanding of the mechanisms underlying the remarkable cellular plasticity that exists in both normal and neoplastic tissue, including in development and tissue regeneration.

Our cell line work is backed up by analysis of heterogeneous cancer stem cell sub-populations in fresh tumour specimens, including comparisons with data on clinical progression. In time, such analyses might enable the tailoring of clinical decisions to the particular distribution of heterogeneous cancer stem cell sub-populations within each individual tumour.

We currently focus on oral squamous cell carcinoma, a tumour type that has an annual worldwide incidence of over 300000 cases and a mortality rate of 48%.

Key questions arising from our work to date, and on which we intend to focus our future efforts, are the following; 1) What is the molecular basis underlying the diversity of cancer stem cell phenotypes in squamous cell carcinoma and their differences in phenotypic plasticity? 2) Are the various cancer stem cell phenotypes reflective of different developmental fates, and dependent on processes that occur in development? 3) Do differences in the incidence of cancer stem cell phenotypes between tumours help drive variation in progression and response to therapy? 4) How can diverse cancer stem cell phenotypes best be modelled in vitro, in order to accurately predict cellular behaviour and response to therapy?

Publications

Key Publications

Biddle, A., Gammon, L., Liang, X., Costea, D. E., and Mackenzie, I. C. (2016). Phenotypic Plasticity Determines Cancer Stem Cell Therapeutic Resistance in Oral Squamous Cell Carcinoma. EBioMedicine 4, 138-145.

Gemenetzidis, E., Gammon, L., Biddle, A., Emich, H., and Mackenzie, I. C. (2015). Invasive oral cancer stem cells display resistance to ionising radiation. Oncotarget 6, 43964-43977.

Shigeishi H, Biddle A, Gammon L, Emich H, Rodini CO, Gemenetzidis E, Fazil B, Sugiyama M, Kamata N and Mackenzie IC (2013). Maintenance of stem cell self-renewal in head and neck cancers requires actions of GSK3β influenced by CD44 and RHAMM. Stem Cells, 2013 Oct; 31(10):2073-83.

Biddle A, Fazil B, Gammon L and Mackenzie IC (2013). CD44 Staining of Cancer Stem-Like Cells Is Influenced by Down-Regulation of CD44 Variant Isoforms and Up-Regulation of the Standard CD44 Isoform in the Population of Cells That Have Undergone Epithelial-to-Mesenchymal Transition. PloS One, 2013; 8(2):e57314.

Biddle, A., Liang, X., Gammon, L., Fazil, B., Harper, L. J., Emich, H., Costea, D. E., and Mackenzie, I. C. (2011). Cancer stem cells in squamous cell carcinoma switch between two distinct phenotypes that are preferentially migratory or proliferative. Cancer Res 71, 5317-5326.

All Publications

Supervision

Primary supervision

• Sophia Lunetto
• Momita Bhuiyan
• Artysha Tailor
• Alice Elisabeth Allegrine Scemama