Jose silva crop 2012

Dr José Silva

Biology of Induced Pluripotency

Email: jcs64@cscr.cam.ac.uk

Laboratory Location:

Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute

Departmental Affiliation:

José is a Wellcome Trust Senior Research Fellow and a member of the Department of Biochemistry, University of Cambridge.

 

Co-workers:

• Yael Costa  • Aliaksandra Radzisheuskaya • Chibeza Agley (joint with Kevin Chalut's lab) • Lawrence Bates  • TY So  • Katie Tremble  Moyra Lawrence  • Hannah Stuart

Education

José received his first degree in Biology from the University of Porto, in Portugal. He joined the GABBA graduate program from University of Porto and then went on to do his PhD studies at Imperial College under the supervision of Professor Neil Brockdorff on heritable silencing mechanisms during mouse development.

Professional History

In 2003 and following his PhD, José moved to Professor Austin Smith's laboratory at the University of Edinburgh as an EMBO post-doctoral fellow to investigate factors involved in nuclear reprogramming. This work has led to the identification of Nanog as the first defined gene with nuclear reprogramming capacity in the conversion of a somatic cell into pluripotency.

In 2008 José started as a group leader at the CSCR investigating the underlying biology of the process of induced pluripotency. His work was initially supported by a Next Generation Award (2008) and subsequently by a Wellcome Trust  Research Fellowship Award (2009). Recently, José was awarded a Wellcome Trust Senior Research Fellowship. He started this in March 2014.

 

Key awards

  • Wellcome Trust Senior Research Fellow, WT101861 (£1,861,906), 2014.
  • Wellcome Trust Research Fellow, WT086692 (£806,000), 2009.
  • Next Generation Stem Cell Research Award, 2008.
  • EMBO Post-doctoral Fellow, ALTF 852-2003, 2003.
  • PhD fellowship from the Ministry of Science and Technology (PRAXIS/XXI/BD/13568/97), Portugal, 1997.

 


Lab Information

The aim of our lab is to understand the underlying biology of the conversion of a somatic epigenome back into a pluripotent epigenome, a process known as induced pluripotency. We are particularly interested in determining the molecular mechanisms by which the key players in this process work. Fully understanding induced pluripotency and better characterising iPS and ES cells is indispensible before these can be used in biomedical applications.


 Do you want to join our Lab?

The Silva Lab welcomes speculative applications from hard-working, highly motivated PhD and Post-Doc candidates with a genuine interest in the fundamental biology of nuclear reprogramming. We have the funds to support the very best Post-Doc applicants. Please address enquiries (include a CV) to jcs64@cam.ac.uk.  


 

Mbd3 facilitates induced pluripotency in a context dependent manner.

Mbd3 facilitates induced pluripotency in a context dependent manner. Click here to read about this work.

 


 

stuart et al

NANOG amplifies STAT3 activation and they synergistically induce the naïve pluripotent program. Click here to read more.


 


 

Nanog tet

Nanog and Tet genes sinergise to induce the naive pluripotent state. Click here to read more.


 

Oct4 NCB

Oct4, the yin and yang of pluripotency (idea and design by Yael Costa). Click here to read more about this work.


 

J. Silva Fig. 1

A colony of stem cells reprogrammed to a pluripotent state from adult brain cells. Inhibitors of the Mek/Erk and GSK3 pathways (2i) in the absence of serum promote the generation of induced pluripotent stem (iPS) cell colonies, shown here. These cells show expression of a pluripotency reporter (green) and reactivation of the silent X chromosome, as demonstrated by the lack of the nuclear red staining body (trimethyl H3K27). For comparison, a cluster of non-reprogrammed cells (non-green) displaying a silent X chromosome (red nuclear body) is shown in the bottom right-hand corner.


 

J. Silva Fig. 5

The image highlights the requirement of Nanog in the early embryo. Whereas the wild type embryo (left) exhibits an inner cell mass (yellow/orange colour) where the pluripotent cells of the embryo are present, the Nanog null embryo fails to generate this population (collaborative work with Dr Jennifer Nichols and Prof. Austin Smith).

PhD Students:


 

Rodrigo

Rodrigo Santos. Rodrigo was a PhD student enrolled in the PhD programme in Experimental Biology and Biomedicine (PDBEB) from the University of Coimbra between 2011-2014 and funded by  the Foundation for Science and Technology in Portugal.​ He is now a Post-Doctoral Research Associate at Horizon Discovery Group PLC, in Cambridge. To see Rodrigo's publications click ​here.


Anouk

Anouk van Oosten. Anouk was a BBSRC funded PhD student in the Silva Lab between 2009-2012. Her PhD degree was awarded in 2012. She has then moved back to the Netherlands to continue her career as a Clinical Research Associate. To see Anouk's publications click here.


Thorold Theunissen

Thorold Theunissen. Thor was a PhD student from the Wellcome Trust - Stem Cell PhD Programme between 2008-2011. His PhD degree was awarded in 2011. From 2012 he moved to the MIT to do a post-doc in the Professor Rudolf Jaenisch laboratory, Whitehead Institute, MIT, USA, being awarded a prestigious Sir Henry Wellcome Post-doctoral Fellowship. To see Thor's publications click here.


J. Silva Fig.4

Ornella Barrandon (2007-2011). PhD awarded in 2011. 2011-Post-doc in Prof. Douglas Melton laboratory, Harvard, USA

 

Plain English

Induced pluripotency is a recently discovered way of making cells equivalent to those present in the embryo and with the ability to form all the tissues in the body from adult cells. It involves introducing genes that are normally present in pluripotent cells into adult cells. The aim of our lab is to understand the biology of this process. We believe that this knowledge will bring us closer to using these cells in regenerative medicine and drug discovery.

Key Publications

  • Santos R, Tosti L, Radzisheuskaya A, Caballero I, Kaji K, Hendrich B, Silva JCR. Mbd3/NuRD facilitates transcription factor induced pluripotency in a context dependent manner. Cell Stem Cell (2014). Jul 3;15(1):102-10. doi:10.1016/j.stem.2014.04.019.
  • Stuart HT, van Oosten AL, Radzisheuskaya A, Martello G, Miller A, Dietmann S, Nichols J, Silva JCR. NANOG amplifies STAT3 activation and they synergistically induce the naïve pluripotent program. Current Biology. (2014). 24, 1–7, February 3 doi: 10.1016/j.cub.2013.12.040.
  • Radzisheuskaya A, Silva JCR. Do all roads lead to Oct4? The emerging concepts of induced pluripotency. Trends in Cell Biology. (2014) May;24(5):275-84. doi: 10.1016/j.tcb.2013.11.010
  • Radzisheuskaya A, Chia GLB, Santos R, Theunissen TW, Castro LFC, Nichols J, Silva JCR. A defined Oct4 level governs cell state transitions of pluripotency entry and differentiation into all embryonic lineages. Nature Cell Biology. 30 April (2013) doi:10.1038/ncb2742.
  • Costa Y, Ding J, Theunissen TW, Faiola F, Hore TA, Shliaha PV, Fidalgo M, Saunders A, Lawrence M, Dietmann S, Das S ,Levasseur DN, Li Z, Xu M, Reik W, Wang J#, Silva JCR#. Nanog-dependent function of Tet1 and Tet2 in establishment of pluripotency. Nature. (2013) doi:10.1038/nature11925.
  • Radzisheuskaya A, Pasque V, Gillich A, Halley-Stott RP, Panamarova M, Zernicka-Goetz M, Surani MA, Silva JCR. Histone variant macroH2A marks embryonic differentiation in vivo and acts as an epigenetic barrier to induced pluripotency. Journal of Cell Science. Oct 17, (2012) doi: 10.1242/​jcs.113019. (2012 Journal of Cell Science paper of the year. Click here to read more)
  • van Oosten AL, Costa Y, Smith A, Silva JCR. Jak/Stat3 signalling is sufficient and dominant over antagonistic cues for the establishment of naïve pluripotency. Nature Communications. May 8;3:827 (2012) doi: 10.1038/ncomms1822.
  • Theunissen TW, Costa Y, Radzisheuskaya A, van Oosten AL, Lavial F, Pain B, CastroLFC, Silva JCR. Reprogramming capacity of Nanog is functionally conserved in vertebrates and resides in a unique homeodomain.Development. (2011) Nov;138(22):4853-65.
  • Theunissen TW, van Oosten AL, Castelo-Branco, G Hall J, Smith A, Silva JCR. Nanog overcomes reprogramming barriers and induces pluripotency in minimal conditions. Current Biology. (2011) Jan 11;21(1):65-71. Epub 2010 Dec 30.
  • Yang J, van Oosten AL, Theunissen TW, Guo G, Silva JCR, Smith A. Stat3 activation is limiting for reprogramming to ground state pluripotency. Cell Stem Cell. (2010) Sep 3;7(3):319-28.
  • Silva J#, Nichols J, Theunissen TW, Guo G, van Oosten AL, Barrandon O, Wray J,Chambers I, Yamanaka S, Smith A#. Nanog is the Gateway to the Pluripotent Ground State. Cell. (2009) Aug 21;138(4):722-37
  • Silva J#, Barrandon O, Nichols J, Theunissen T, Kawaguchi J, Smith A#. Promotion of Reprogramming to Ground State Pluripotency by Signal Inhibition. PLoS Biology. (2008) 6(10): e253 doi:10.1371/journal. pbio.0060253.(Article chosen by PLOS Biology's Editors and Editorial Board representative of the high quality research published in the journal over the last decade. click here to read more)
  • Silva J, Chambers I, Pollard S, Smith A. Nanog promotes transfer of pluripotency after cell fusion. Nature(2006) Jun 22;441(7096):997-1001.

(#) joint corresponding/senior authors 


 Click below for:


The Wellcome Trust is the main sponsor of the Lab. The lab is also sponsored by the Medical Research Council, Isaac Newton Trust and FCT(Portugal).


 

From left to right: Rodrigo, Alex, José, Moyra, Hannah and Yael
Lab photo 2013

Lab photo 2013, Gonville & Caius College, Cambridge.

Web design by Studio 24 / Back to top