BSc (Hons)., Ph.D., FHEA
For a recent discussion about Thalidomide research and some of the goals we have please see the following article published in 'The Conversation' and the 'Independent':
August 2013 Senior Lecturer, School of Medical Sciences, University of Aberdeen.
August 2007 Lecturer, School of Medical Sciences, University of Aberdeen.
2006 - Fellow of the Higher Education Academy (FHEA)
2005 - CASLAT (Cerificate of Advanced Study in Learning and Teaching), Imperial College
2004 - 2007 Lecturer. NHLI Division, Faculty of Medicine. Imperial College London.
2001 - 2003 Postdoctoral Fellow. Cancer Research UK, London. UK, with Dr Julian Lewis studying zebrafish gut development.
1998 - 2001 Postdoctoral Fellow. Department of Genetics and Development, Columbia University, New York. USA, with Dr Ed Laufer studying TGFbeta signalling in chick limb development (funded by HFPSO Long-Term Fellowship)
1998 - Ph.D (Developmental Biology), University College London (with Profs Lewis Wolpert and Cheryll Tickle)
1994 - B.Sc. (Hons) Human Biology, Kings College London
Research in the lab is focused on determining the mechanisms underlying thalidomide-induced teratogenesis; identifying non-teratogenic forms of thalidomide; screening drugs to identify their function/s and action/s; studying how blood vessels are involved in controlling normal and abnormal limb development; studying the role of the YAP signaling pathway in embryonic development; using the chicken embryo to produce a model of Clubfoot to understand how this common birth anomaly comes about; and understanding how birth defects come about in general.
For a recent discussion written for the public about Thalidomide and some of the goals we have please see the following article published in 'The Conversation' and also in the 'Independent':
For recent discussions written for the public on other topics related to birth defects please see the following articles:
We have demonstrated (Therapontos et al., 2009) how thalidomide can cause limb malformations. The drug was used as a non-addictive, non-barbiturate sedative and was also prescribed to pregnant women suffering from morning-sickness (typically, but not exclusively, between weeks 5-10). Tragically over 10000 children were born with severe birth defects, notably, and commonly, limb malformations.
Using analogs and metabolic byproducts of the drug, we showed that the antiangiogenic action of the drug causes limb defects, through preventing blood vessel migration into the developing limb bud. We further showed how the drug exerts its antiangiogenic effect, through preventing endothelial cell proliferation and migration and thus, preventing vessel tube networks from forming. At the time the limb forms (which in humans is around 5-8 weeks) it has a highly changeable vessel pattern - whereas the rest of the body has a stable vascular network. Thalidomide therefore may prevent new vessel outgrowth, which then causes an increase in cell death and loss of limb signalling pathways, stopping limb formation.
Therapontos C, Erskine L, Gardner ER, Figg WD, Vargesson, N. (2009). Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation. Proc. Natl. Acad. Sci USA. 106, 8573-8578. DOI:10.1073/pnas.0o01505106.
This work received wide spread media interest, including:
A large number of newspapers, including The Independent, The Daily Mail, The Scotsman, The Press & Journal, and several Radio stations.
The work was also featured in Nature News:
Making safer Thalidomide alternatives:
We are also interested in identifying thalidomide alternatives that retain the clinical benefits of the drug (successfully used to treat Leprosy and Multiple Myeloma) with lessened or no side-effect (eg: birth defect, peripheral neuropathy). To this end we have compared the effects of Thalidomide with its structural analogs, Lenalidomide and Pomalidomide. We demonstrated that the minor structural changes in Pomalidomide make this compound more anti-inflammatory (and not teratogenic in chicken and zebrafish embryos) at lower concentrations than Thalidomide and Lenalidomide (Mahony et al., 2013). We have also screened fluorinated thalidomide analogs and demonstrated differences in analog activities (Beedie et al., 2015). These findings validate making structural changes to Thalidomide to try to find safer alternatives.
Following on from this work we have screened over 80 thalidomide analogs in our zebrafish and chicken embryo assays and identified several with actions that retain clinical advantages (ie: anti-inflammatory) with reduced or no observable teratogenic effects in zebrafish and chicken embryos (Beedie et al., 2016). Some of these analogs are being patented.
Mahony C, Erskine, Niven J, Grieg NH, Figg WD, Vargesson N. (2013). Pomalidomide is nonteratogenic in chicken and zebrafish embryos and nonneurotoxic invitro. Proc. Natl. Acad. Sci USA. 110, 12703-8. doi: 10.1073/pnas.1307684110
Beedie SL, Peer CJ, Pisle S, Gardner ER, Mahony C, Barnett S, Ambrozak A, Gütschow M, Chau CH, Vargesson N, Figg WD. (2015). Anticancer properties of a novel class of tetrafluorinated thalidomide analogues. Mol Cancer Ther 14:2228-2237. doi: 10.1158/1535-7163.MCT-15-0320.
Beedie SL, Rore HM, Barnett S, Chau CH, Luo W, Greig NH, Figg WD, Vargesson N. (2016). In vivo screening and discovery of novel candidate thalidomide analogs in the zebrafish and chicken embryo models systems. Oncotarget. 2016 May 31;7(22):33237-45. doi: 10.18632/oncotarget.8909.
This work was mentioned in The Sunday Times, 4 August 2013.
And on realradio.co.uk/scotland.
Review articles on Thalidomide History and Mechanisms of Action:
Vargesson N. (2009). Thalidomide-induced limb defects: resolving a 50-year-old puzzle. Bioessays. 31(12):1327-36. doi: 10.1002/bies.200900103.
Vargesson N. (2013). Thalidomide embryopathy: an enigmatic challenge. ISRN Developmental Biology Volume 2013 (2013), Article ID 241016,. http://dx.doi.org/10.1155/2013/241016
Vargesson N. (2015). Thalidomide-induced teratogenesis: history and mechanisms. Birth Defects Res C Embryo Today. 105(2):140-56. doi: 10.1002/bdrc.21096.
Media Interviews/Discussions about our Thalidomide research:
2009 - The Material World (BBC Radio 4) - http://www.bbc.co.uk/programmes/b00k9hlz#synopsis
2010 - The Diane Rehm Show (US Radio) - http://thedianerehmshow.org/shows/2010-09-16/thalidomide-and-fda
2010 - The New York Times - interviewed by Carl Zimmer
2011 - The Naked Scientists (BBC Radio) - http://www.thenakedscientists.com/HTML/content/interviews/interview/1785/
2012 - German Public Radio - http://www.dradio.de/dlf/sendungen/hintergrundpolitik/1917460/
2013 - The Today Program (BBC Radio 4) - Thalidomide: Were more babies affected?
2013 - BBV TV News - Thalidomide: Were more babies affected? (Oct 14, 2013)
2013 - BBC News Website - http://www.bbc.co.uk/news/health-24472269
2013 - The Naked Scientists (BBC Radio) -
2015 - SHMU Radio - 'Talking Science' (Jan 27, 2015)
Some images of my thalidomide work is featured in a Fine Art Exhibition (and subsequent Book) by the renowned artist, Taryn Simon. The Exhibition is entitled: ‘A Living Man Declared Dead and Other Chapters’ and toured the world throughout 2011 and 2012.
Media articles about Thalidomide
2015 - The Conversation
2015 - The Independent
Degree Programme Co-ordinator - Human Embryology and Developmental Biology
Course Co-ordinator - DB3006 Principles of Developmental and Reproductive Biology
Course Co-ordinator - DB4002 Evolution and Development
Teach on SM2001, SM2501, SM3002, DB3006, DB3804, DB4002, DB4002, PA4005
-Editorial Board Member, Reproductive Toxicology (2015-2019).
-Guest Editor for a Special Issue of Reproductive Toxicology entitled 'Developmental Angiogenesis'
Submissions open until December 2016. Publication in early 2017.
-Organiser, 14th International Conference on Limb Development and Regeneration to be held at the University of Edinburgh between July 23-26, 2017.
-Member, Sarcoma UK Research Advisory Committee (2016-2019) - which oversees Grant Application reviewing and funding.
-Advisor, World Health Organisation 'Diagnostic Criteria and Mechanisms of Action of Thalidomide' - Feb 2014. Meeting report with recommendations: http://www.who-umc.org/graphics/28280.pdf
Elected Member, University Senate (2008-2013) (2016-2020)
Senate Assessor to University Court (2009-2013)
Member, Governance and Nominations Committee (reports to University Court; 2012-2013)
Member, IMS Athena SWAN Team for Bronze Award (2015-present)
I am looking for motivated, self-funded PhD students to join my group. Projects are available to study:
1. Mechanisms of thalidomide teratogenesis
2. Identification of non-teratogenic forms of thalidomide
4. Mechanisms underlying limb proximo-distal outgrowth and pattern
5. Control of vascular patterning in the embryo
6. Role of YAP signalling in embryonic development
7. Action of Primodos in the vertebrate embryo