Prof Austin Smith

Stem Cell Potency

Laboratory Location:

Wellcome Trust Centre for Stem Cell Research, Smith Lab Members

Departmental Affiliation:

Department of Biochemistry, University of Cambridge

Co-workers:

• Melanie Rittirsch (Lab Manager)
• Joerg Betschinger • James Clarke • Elizabeth Cook • Rosalind Drumond • Ge Guo • Tuzer Kalkan • Masaki Kinoshita • Raja Kittappa • Martin Leeb • Graziano Martello • Gillian Morrison • Carla Mulas • Jignesh Tailor • Rika Takashima • Yasuhiro Takashima • Elena Tzouanacou • Yaoyao Chen

Learn more about Prof Austin Smith

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 Centre for Stem Cell Research. 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.

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.

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

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

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Prof Austin Smith

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) The transcriptional and epigenomic foundations of ground state pluripotency. Cell Apr; 149(3):590-604
Guo G, Yang J, Nichols J, Hall JS, Eyres I, Mansfield W and Smith AG. (2009) Klf4 reverts developmentally programmed restriction of ground state pluripotency. Development Apr; 136(7): 1063-1069
Pollard SM, Yoshikawa K, Clarke ID, Danovi D, Stricker S, Russell R, Bayani J, Head R, Lee M, Bernstein M, Squire JA, Smith AG, Dirks P. (2009) Glioma stem cell lines expanded in adherent culture have tumor-specific phentotypes and are suitable for chemical and genetic screens. Cell Stem Cell; Jun 5; 4(6): 568-580
Silva J, Nichols J, Theunissen T, Guo G, Van Oosten A, Barrandon O, Wray J, Yamanaka S, Chambers I, Smith A. (2009) Nanog is the gateway to the pluripotent ground state. Cell Aug 21; 138(4): 722-737
Buehr M, Meek S, Blair K, Silva J, McLay R, Hall J, Ying Q-L and Smith AG. (2008) Capture of authentic embryonic stem cells from rat blastocysts. Cell 135: 1287-1298
Silva J, Barrandon O, Nichols J, Kawaguchi J, Theunissen TW, Smith AG. (2008) Promotion of reprogramming to ground state pluripotency by signal inhibition. PLoS Biology 6: 2237-2247
Ying QL, Wray J, Nichols J, Batlle-Morera L, Doble B, Woodgett J, Cohen P. and Smith A. (2008) The ground state of embryonic stem cell self-renewal Nature 453: 519-523