Douglas Strathdee - Transgenic Technology

Introduction

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During the development of cancer, cells frequently lose attributes of their tissue of origin and acquire some of the characteristics of stem cells, a process termed anaplasia. The aim of the research in our lab is to use stem cells to model the processes underlying cancer and to uncover the roles that novel stem cell and reprogramming factors play in the development of the disease. Using embryonic stem (ES) cells we are developing and improving models of human cancer. The targeted genetic modification of such cells allows us to study genes involved in cancer in fine detail so as to better understand their normal function and how these functions are compromised during the development of cancer.

Once modified ES cell lines are established, not only can gene function be analysed in the stem cells themselves but these cells can be differentiated into a wide variety of different cell types to allow the study of basic disease mechanisms in different tissues and potentially to establish screens for drug discovery. In addition, it is possible to reverse the differentiation process and reprogramme a variety of somatic cells to induced pluripotential stem (iPS) cells. This process is reminiscent of anaplasia, the loss of differentiation seen in cancer. Genes crucial for this type of reprogramming are often involved in cancer development.

Lab Report

icon Transgenic Technology Report

Key Publications

Strathdee D, Whitelaw CB, Clark AJ. Distal transgene insertion affects CpG island maintenance during differentiation. J Biol Chem. 283, 11509-15, 2008

Strathdee D, Ibbotson H, Grant SG. Expression of transgenes targeted to the Gt(ROSA)26Sor locus is orientation dependent. PLoS One 1, e4, 2006

Brown K, Strathdee D, Bryson S, Lambie W, Balmain A. The malignant capacity of skin tumours induced by expression of a mutant H-ras transgene depends on the cell type targeted. Curr Biol. 8, 516-24, 1998

Biography

Education and qualifications

1995: PhD, University of Glasgow, Supervisor Allan Balmain
1989: BSc, Immunology (Honours), University of Glasgow

Appointments

2009-present: Head of Transgenic Technology, Cancer Research UK Beatson Institute, Glasgow
2004-2009: Senior Research Associate, Wellcome Trust Sanger Institute
2000-2004: Postdoctoral Fellow, University of Edinburgh
1996-2000: Research Scientist, Roslin Institute

Recent Publications

2016

Birch J, Clarke CJ, Campbell AD, Campbell K, Mitchell L, Liko D, Kalna G, Strathdee D, Sansom OJ, Neilson M, Blyth K, Norman JC. The initiator methionine tRNA drives cell migration and invasion leading to increased metastatic potential in melanoma. Biol Open. 2016 Aug 19. pii: bio.019075. doi: 10.1242/bio.019075. [Epub ahead of print]

Walton J, Blagih J, Ennis D, Leung E, Dowson S, Farquharson M, Tookman LA, Orange C, Athineos D, Mason S, Stevenson D, Blyth K, Strathdee D, Balkwill FR, Vousden KH, Lockley M, McNeish IA.CRISPR/Cas9-mediated Trp53 and Brca2 knockout to generate improved murine models of ovarian high grade serous carcinoma. Cancer Res. 2016 Aug 16. pii: canres.1272.2016. [Epub ahead of print]

2015

Cadalbert LC, Ghaffar FN, Stevenson D, Bryson S, Vaz FM, Gottlieb E, Strathdee D. Mouse Tafazzin Is Required for Male Germ Cell Meiosis and Spermatogenesis. PLoS One 10: e0131066, 2015

Cardaci S, Zheng L, MacKay G, van den Broek NJ, MacKenzie ED, Nixon C, Stevenson D, Tumanov S, Bulusu V, Kamphorst JJ, Vazquez A, Fleming S, Schiavi F, Kalna G, Blyth K, Strathdee D, Gottlieb E. Pyruvate carboxylation enables growth of SDH-deficient cells by supporting aspartate biosynthesis. Nat Cell Biol 17: 1317-26, 2015

2013

Cheung EC, Athineos D, Lee P, Ridgway RA, Lambie W, Nixon C, Strathdee D, Blyth K, Sansom OJ, Vousden KH. TIGAR is required for efficient intestinal regeneration and tumorigenesis. Dev Cell 25: 463-77, 2013

Strathdee D, Whitelaw CB. TT2013 meeting report: the Transgenic Technology meeting visits Asia for the first time. Transgenic Res 22: 667-71, 2013

2012

Schachtner H, Li A, Stevenson D, Calaminus SD, Thomas SG, Watson SP, Sixt M, Wedlich-Soldner R, Strathdee D, Machesky LM. Tissue inducible Lifeact expression allows visualization of actin dynamics in vivo and ex vivo. Eur J Cell Biol 91(11-12): 923-9, 2012

Lab Members

Post-doc

Eve Anderson

Scientific Officer

Farah Hughes

PhD Student

Nicola Laprano

Research

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Read more about the Research Groups working at the Beatson Institute.

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Seminars

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Find out more about our seminars including our Distinguished Seminar Programme.

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