Dr José Silva
Biology of Induced Pluripotency
José is a Wellcome Trust Research Fellow and a member of the Department of Biochemistry, University of Cambridge.
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.
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 Career Development Fellowship Award (2009).
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
Sources of funding: Wellcome Trust • Next Generation Award • Isaac Newton Trust
Plain EnglishInduced 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.
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- 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. (2013) Dec 23. pii: S0962-8924(13)00223-7. 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.
- 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.
(#) joint corresponding/senior authors