Dr José Silva
Biology of induced pluripotency
Laboratory: Cambridge Stem Cell Institute, Gleeson Building.
Departmental Affiliation: Biochemistry
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 PI at the SCI investigating the biology 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 May 2014.
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).
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Panel depicting the appearance of induced pluripotent stem cells (green) from an identified pre-determined to reprogram cell population (red). Non-red cells (grey and blue only) failed to acquire reprogramming competence. (Credit Chibeza Agley)
My lab investigates the underlying biology of reprogramming a differentiated cell identity back into a naïve pluripotent stem cell identity, a process known as induced pluripotency. We are interested in determining the molecular mechanisms by which the key reprogramming players establish the naïve pluripotent stem cell identity and in deciphering the transcriptional and epigenetic regulation taking place during this process. This is of fundamental relevance to understanding the biology of naïve pluripotent stem cells, learning how to induce a bonafide cell identity change and generating better naïve pluripotent stem cells to use as a platform for studies in in vitro developmental biology and in applications for regenerative medicine.
Chibeza Agley (joint with Chalut's lab), Lawrence Bates, Yael Costa, Sergey Gladkou, Charlotte Handford, Elsa Sousa, Hannah Stuart, Katie Tremble.
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. The lab has the funds to support the very best Post-Doc applicants. Please address enquiries (include a CV) to email@example.com.
Former group members
Aliaksandra Radzisheuskaya • Moyra Lawrence • Rodrigo Santos • Anouk van Oosten • Thorold Theunissen • Ornella Barrandon • Moyra Lawrence
Saeed Kayhanian • Mariana Alves • Jia Yi Fong • James Patterson • Hannah Stuart
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.
- Santos R, Tosti L, Radzisheuskaya A, Caballero I, Kaji K, Hendrich B, Silva JCR. Mbd3/NuRD facilitates induced pluripotency in a context dependent manner. Cell Stem Cell (2014). 15(1):102-10. PMCID:PMC4082719
- 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 (2013) 15(6):579-90. PMCID:PMC3671976
- Costa Y, Ding J, Theunissen T, Faiola F, Hore T, Shliaha P, Fidalgo M, Saunders A, Lawrence M, Dietmann S, Das S, Levasseur D, Li Z, Xu M, Reik W, Wang J, Silva JCR. Nanog-dependent function of Tet1 and Tet2 in establishment ofpluripotency. Nature (2013) 495(7441):370-4. PMCID:PMC3606645
- 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) 138(4):722-37. PMCID:PMC3437554
- 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) Oct 21;6(10):e253. PMCID:PMC2570424