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Dr J Da Silva
Applications accepted all year round
Awaiting Funding Decision/Possible External Funding
About the Project
Understanding the biology of nuclear reprogramming, which is the conversion of adult cells back into an embryonic stem cell state, is a fundamental question in biology with huge potential for applications in biomedicine. Recent advances in the field have started to identify genes that instruct this genome plasticity. We previously identified Nanog as a limiting factor for the conversion of Neural Stem (NS) cells to pluripotency after cell fusion to Embryonic Stem (ES) cells. Subsequently, induction of mouse embryonic fibroblasts to a pluripotent stem (iPS) cell state was achieved by expression of four factors, cMyc, Oct4, Klf4 and Sox2, after retroviral infection. Despite recent advances, much is still unknown regarding the basic biology of nuclear reprogramming. After the landmark discovery of iPS cells we have developed a system whereby somatic cells are reprogrammed rapidly and efficiently to full pluripotency by chemical inhibition. To follow up on this work I am proposing a project aiming to discover additional players in the nuclear reprogramming process.
References
•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
•Nichols J, Silva J, Roode M, Smith A. Suppression of Erk signaling promotes ground state pluripotency in the mouse embryo. Development. 2009 doi:10.1242/dev.038893.
•Banito A, Rashid ST, Acosta JC, Li S, Pereira CF, Geti I, Pinho S, Silva JC, Azuara V, Walsh M, Vallier L, Gil J. Senescence impairs successful reprogramming to pluripotent stem cells. Genes & Development. 2009 doi:10.1101/gad.1811609
•Buehr M, Meek S, Blair K, Yang J, Ure J, Silva J, McLay R, Hall J, Ying Q, Smith A. Capture of Authentic Embryonic Stem Cells from Rat Blastocysts. Cell. 2008 Dec 26;135(7):1287-98.
•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.
•Silva J, Smith A. Capturing pluripotency. Cell. 2008 February 22; 132(4):532-6.
•Chambers I, Silva J, Colby D, Nichols J, Robertson M, Nijmeijer B, Vrana J, Grotewold L, Smith A. Nanog safeguards pluripotency and mediates germline development. Nature. 2007 Dec 20;450(7173): 1230-4.
•Silva J, Chambers I, Pollard S, Smith A. Nanog promotes transfer of pluripotency after cell fusion. Nature. 2006 Jun 22;441(7096):997-1001. Epub 2006 Jun 14.
•Nichols J, Silva J, Roode M, Smith A. Suppression of Erk signaling promotes ground state pluripotency in the mouse embryo. Development. 2009 doi:10.1242/dev.038893.
•Banito A, Rashid ST, Acosta JC, Li S, Pereira CF, Geti I, Pinho S, Silva JC, Azuara V, Walsh M, Vallier L, Gil J. Senescence impairs successful reprogramming to pluripotent stem cells. Genes & Development. 2009 doi:10.1101/gad.1811609
•Buehr M, Meek S, Blair K, Yang J, Ure J, Silva J, McLay R, Hall J, Ying Q, Smith A. Capture of Authentic Embryonic Stem Cells from Rat Blastocysts. Cell. 2008 Dec 26;135(7):1287-98.
•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.
•Silva J, Smith A. Capturing pluripotency. Cell. 2008 February 22; 132(4):532-6.
•Chambers I, Silva J, Colby D, Nichols J, Robertson M, Nijmeijer B, Vrana J, Grotewold L, Smith A. Nanog safeguards pluripotency and mediates germline development. Nature. 2007 Dec 20;450(7173): 1230-4.
•Silva J, Chambers I, Pollard S, Smith A. Nanog promotes transfer of pluripotency after cell fusion. Nature. 2006 Jun 22;441(7096):997-1001. Epub 2006 Jun 14.
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