Austin Smith new

Professor Austin Smith

Stem Cell Potency

Email: agssec@cscr.cam.ac.uk

Laboratory Location:

Wellcome Trust Centre for Stem Cell Research, Smith Lab Members

Departmental Affiliation:

Department of Biochemistry, University of Cambridge

Tel 01223 (7)60233

Co-workers:

Nicholas Bredenkamp • Yaoyao Chen • James ClarkeRosalind DrumondGe Guo • Fatima Junaid • Tuzer KalkanMasaki Kinoshita • Martin Leeb Meng Amy Li • Harry Leitch • Carla Mulas  •  Samuel Myers  • Meryem RalserMariya Rostovskaya  • Stanley Strawbridge • Rika Takashima •Yasuhiro Takashima •

Personal Information

Professor Austin Smith was captivated by pluripotency and stem cell self-renewal by undergraduate lectures from Professor Chris Graham in Oxford. He pursued this interest through PhD studies with Martin Hooper at the University of Edinburgh from 1982-86. Following postdoctoral research at the University of Oxford with John Heath, he returned to Edinburgh in 1990 as a Group Leader at the Centre for Genome Research. In 1996, he was appointed Director of the Centre, which under his leadership became the first Institute for Stem Cell Research in the United Kingdom. He was awarded an MRC Research Professorship in 2003. In 2006 he moved to the University of Cambridge where he is currently Director of the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute. He coordinated the European Commission integrated project EuroStemCell (2004-2008) and currently coordinates the EuroSyStem project (2008-2012). Professor Smith is a Fellow of the Royal Society of Edinburgh, an elected member of EMBO, and a Fellow of the Royal Society of London. In 2010 he was awarded the Louis Jeantet Prize.


Research Interests:

We study embryonic stem (ES) cells and derivative tissue stem cells. Our goal is to understand the molecular foundations of self-renewal and commitment. We are investigating determinants of the decision to retain or exit pluripotency and the mechanism of lineage choice. We are also interested in the relationship between stem cell lines propagated in culture and progenitor cells in vivo. We are analysing the degree of conservation between pluripotent cells from different mammalian species in order to determine whether there are generic principles underlying embryonic stem cell properties. We hope to apply the knowledge gained to control the derivation, expansion and differentiation of human stem cells. We interact with clinical scientists and bioindustry to facilitate uptake and use of stem cells in the study of disease mechanisms and for drug discovery.

A. Smith Fig. 1

Figure: Hypothetical scheme for loss of pluripotency and lineage commitment.

Stem cells expanded from the human embryonic hindbrain stably retain regional specification and high neurogenic potency: http://www.sms.cam.ac.uk/media/1506157 

 

Plain English

In the early embryo a small group of cells acquire the ability to make all cell types of the animal. This property is called pluripotency. It is possible to grow pluripotent cells in the laboratory. These are called embryonic stem cells. Research with mouse embryonic stem cells over the past 10 years has identified the master genes that control pluripotency. However, there is still an important part that we do not understand well; how do the pluripotent cells choose to make different types of tissue? We study this question in mouse, rat and human. An aim of this work is to obtain human embryonic stem cells with well understood properties that can provide a reliable foundation for pharmaceutical research and clinical applications.

Key Publications

  • Identification of the missing pluripotency mediator downstream of leukaemia inhibitory factor. Martello G, Bertone P, Smith A. EMBO Journal 32(19):2561-2574 August 2013
  • Exit from pluripotency is gated by intracellular redistribution of the bHLH transcription factor Tfe3. Betschinger J, Nichols J, Dietmann S, Corrin PD, Paddison PJ, Smith A (2013) Cell 
  • Esrrb Is a Pivotal Target of the Gsk3/Tcf3 Axis Regulating Embryonic Stem Cell Self-Renewal. Martello G, Sugimoto T, Diamanti E, Joshi A, Hannah R, Ohtsuka S, Gottgens B, Niwa H, Smith A. (2012)  Cell Stem Cell, Volume 11, Issue 4, 491-504, 5 October 2012
  • The transcriptional and epigenomic foundations of ground state pluripotency. Marks H, Kalkan T, Menafra R, Denissov S, Jones K, Hofemeister H, Nichols J, Kranz A, Francis Stewart A, Smith A and Stunnenberg HG. (2012)  Cell Apr; 149(3):590-604
  • Klf4 reverts developmentally programmed restriction of ground state pluripotency. Guo G, Yang J, Nichols J, Hall JS, Eyres I, Mansfield W and Smith AG. (2009) Development Apr; 136(7): 1063-1069
  • Capture of authentic embryonic stem cells from rat blastocysts. Buehr M, Meek S, Blair K, Silva J, McLay R, Hall J, Ying Q-L and Smith AG. (2008) . Cell 135: 1287-1298
  • The ground state of embryonic stem cell self-renewal. Ying QL, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P. and Smith A. (2008) Nature 453: 519-523

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