Professor Anna Philpott University positionReader Professor Anna Philpott is pleased to consider applications from prospective PhD students. DepartmentsInstitutesHutchison/Medical Research Council Research Centre Home pagehttp://www.oncology.cam.ac.uk/researc... Research ThemesInterestsOur laboratory is interested in understanding the coordination of cell proliferation with cell fate determination and differentiation in development, stem cells and reprogramming, focusing particularly on the nervous system (as well as in endocrine gut and pancreas). Recently, we have been investigating cell cycle regulation of basic helix-loop-helix proneural transcription factors in a variety of systems. By combining work in the experimentally tractable Xenopus frog embryo with genetically modified mouse models, we study developmental effects of cell cycle modulation in simple and complex nervous systems. These varied approaches allow us to gain a deeper mechanistic understanding of the many ways that cell cycle and differentiation machineries are linked in the nervous system. Moreover, we are using our finding to enhance neuron generation in vitro from ES cells and after reprogramming of fibroblasts, and to investigate potential therapies for cancers of the nervous system. Research Focus
EquipmentImmunohistochemistry Xenopus embryos as a model system for cell cycle and neuronal differentiation Collaborators
Associated News ItemsKey publicationsR. Azzarelli, C. Hurley, M. Sznurkowska, I. Gamper, F. Ali, L. McCracken, C. Hindley, F. McDuff, L. Hardwick, K. Jones, R. Kemp, B. Simons, M. Huch, G. Evan, D. Winton, A. Philpott. (2017), “Neurogenin3 phosphorylation controls pancreatic endocrine differentiation and maintenance of ?-cell function. ” Developmental Cell 41: 274-286 G.S. McDowell , A. Philpott (2016), “New Insights Into the Role of Ubiquitylation of Proteins.” International review of Cell and Molecular Biology 325:35-88 Hardwick LJ, Davies JD, Philpott A. (2016), “MyoD phosphorylation on multiple C terminal sites regulates myogenic conversion activity. ” Biochem Biophys Res Commun. 481: 97-103. Azzarelli R, Hardwick LJ, Philpott A. (2015), “Emergence of neuronal diversity from patterning of telencephalic progenitors.” Wiley Interdiscip Rev Dev Biol. May-Jun;4(3):197-214 Hardwick LJ, Philpott A (2015), “ Multi-site phosphorylation regulates NeuroD4 activity during primary neurogenesis: a conserved mechanism amongst proneural proteins.” Neural Dev 10:15 L.A. Wylie, L.J.A. Hardwick, T. D. Papkovskaia, C. J. Thiele and A. Philpott (2015), “Ascl1 phospho-status regulates neuronal differentiation in a Xenopus developmental model of neuroblastoma. ” Disease Models and Mechanisms 8:429-41 L.J. Hardwick, A. Philpott (2015), “Multi-site phosphorylation regulates NeuroD4 activity during primary neurogenesis: a conserved mechanism amongst proneural proteins.” Neural Development 10:15 Philpott A (2015), “Multi-site phospho-regulation of proneural transcription factors in development and reprogramming. ” Neurogenesis (Austin) 2: e1049733 Wylie LA, Hardwick LJA, Papkovskaia TD, Thiele CJ, Philpott A (2015), “Ascl1 phospho-status regulates neuronal differentiation in a Xenopus developmental model of neuroblastoma. ” Dis Model Mech 8:429-41 Ali FR, Cheng K, Kirwan P, Metcalfe S, Livesey FJ, Barker RA Philpott A (2014), “The phosphorylation status of Ascl1 is a key determinant of neuronal differentiation and maturation in vivo and in vitro” Development 141, 2216-2224 G. S. McDowell, C. J. Hindley, G. Lippens, I. Landrieu and A. Philpott. (2014), “Phosphorylation in intrinsically disordered regions regulates the activity of Neurogenin2 ” Biomed Central Biochemistry 6 :24 Philpott A, Winton DJ (2014), “Lineage selection and plasticity in the intestinal crypt” Curr Opinion Cell Biol 31C:39-45 Publications2014Ali FR, Cheng K, Kirwan P, Metcalfe S, Livesey FJ, Barker RA, Philpott A (2014), “The phosphorylation status of Ascl1 is a key determinant of neuronal differentiation and maturation in vivo and in vitro.” Development Details Hardwick LJ, Philpott A (2014), “Nervous decision-making: to divide or differentiate.” Trends Genet Details 2013Hindley C, Philpott A (2013), “The cell cycle and pluripotency.” Biochem J 451(2):135-43 Details McDowell GS, Philpott A (2013), “Non-canonical ubiquitylation: mechanisms and consequences.” Int J Biochem Cell Biol 45(8):1833-42 Details 2012Hindley C, Ali F, McDowell G, Cheng K, Jones A, Guillemot F, Philpott A (2012), “Post-translational modification of Ngn2 differentially affects transcription of distinct targets to regulate the balance between progenitor maintenance and differentiation.” Development 139(10):1718-23 Details Hindley C, Philpott A (2012), “Co-ordination of cell cycle and differentiation in the developing nervous system.” Biochem J 444(3):375-82 Details Roark R, Itzhaki L, Philpott A (2012), “Complex regulation controls Neurogenin3 proteolysis.” Biol Open 1(12):1264-72 Details Wylie L, Philpott A (2012), “Neuroblastoma progress on many fronts: the Neuroblastoma Research Symposium.” Pediatr Blood Cancer 58(4):649-51 Details 2011Ali F, Hindley C, McDowell G, Deibler R, Jones A, Kirschner M, Guillemot F, Philpott A (2011), “Cell cycle-regulated multi-site phosphorylation of Neurogenin 2 coordinates cell cycling with differentiation during neurogenesis.” Development 138(19):4267-77 Details Hindley CJ, McDowell GS, Wise H, Philpott A (2011), “Regulation of cell fate determination by Skp1-Cullin1-F-box (SCF) E3 ubiquitin ligases.” Int J Dev Biol 55(3):249-60 Details Murai K, Philpott A, Jones PH (2011), “Hes6 is required for the neurogenic activity of neurogenin and NeuroD.” PLoS One 6(11):e27880 Details 2010Almeida AD, Wise HM, Hindley CJ, Slevin MK, Hartley RS, Philpott A (2010), “The F-box protein Cdc4/Fbxw7 is a novel regulator of neural crest development in Xenopus laevis.” Neural Dev 5:1 Details McDowell GS, Kucerova R, Philpott A (2010), “Non-canonical ubiquitylation of the proneural protein Ngn2 occurs in both Xenopus embryos and mammalian cells.” Biochem Biophys Res Commun 400(4):655-60 Details 2009Naylor RW, Collins RJ, Philpott A, Jones EA (2009), “Normal levels of p27 are necessary for somite segmentation and determining pronephric organ size.” Organogenesis 5(4):201-10 Details Vosper JM, McDowell GS, Hindley CJ, Fiore-Heriche CS, Kucerova R, Horan I, Philpott A (2009), “Ubiquitylation on canonical and non-canonical sites targets the transcription factor neurogenin for ubiquitin-mediated proteolysis.” J Biol Chem 284(23):15458-68 Details 2008Movassagh M, Philpott A (2008), “Cardiac differentiation in Xenopus requires the cyclin-dependent kinase inhibitor, p27Xic1.” Cardiovasc Res 79(3):436-47 Details Philpott A (2008), “Division versus differentiation in the early Xenopus embryo.” SEB Exp Biol Ser 59:145-65 Details Philpott A, Yew PR (2008), “The Xenopus cell cycle: an overview.” Mol Biotechnol 39(1):9-19 Details 2007Boix-Perales H, Horan I, Wise H, Lin HR, Chuang LC, Yew PR, Philpott A (2007), “The E3 ubiquitin ligase skp2 regulates neural differentiation independent from the cell cycle.” Neural Dev 2:27 Details Cosgrove RA, Philpott A (2007), “Cell cycling and differentiation do not require the retinoblastoma protein during early Xenopus development.” Dev Biol 303(1):311-24 Details Murai K, Vernon AE, Philpott A, Jones P (2007), “Hes6 is required for MyoD induction during gastrulation.” Dev Biol 312(1):61-76 Details Vosper JM, Fiore-Heriche CS, Horan I, Wilson K, Wise H, Philpott A (2007), “Regulation of neurogenin stability by ubiquitin-mediated proteolysis.” Biochem J 407(2):277-84 Details 2006Lin HR, Chuang LC, Boix-Perales H, Philpott A, Yew PR (2006), “Ubiquitination of cyclin-dependent kinase inhibitor, Xic1, is mediated by the Xenopus F-box protein xSkp2.” Cell Cycle 5(3):304-14 Details Nguyen L, Besson A, Heng JI, Schuurmans C, Teboul L, Parras C, Philpott A, Roberts JM, Guillemot F (2006), “p27kip1 independently promotes neuronal differentiation and migration in the cerebral cortex.” Genes Dev 20(11):1511-24 Details Vernon AE, Movassagh M, Horan I, Wise H, Ohnuma S, Philpott A (2006), “Notch targets the cdk inhibitor Xic1 to regulate differentiation but not cell cycle in neurons” EMBO Reports, 7:643-648 Details 2005Philpott A, Yew PR (2005), “The Xenopus cell cycle: an overview.” Methods Mol Biol 296:95-112 Details Sangrithi MN, Bernal JA, Madine M, Philpott A, Lee J, Dunphy WG, Venkitaraman AR (2005), “Initiation of DNA replication requires the RECQL4 protein mutated in Rothmund-Thomson syndrome.” Cell 121(6):887-98 Details 2004Richard-Parpaillon L, Cosgrove RA, Devine C, Vernon AE, Philpott A (2004), “ G1/S phase cyclin-dependent kinase overexpression perturbs early development and delays tissue-specific differentiation in Xenopus” Development 131:2577-86 Details 2003Cremisi F, Philpott A, Ohnuma S (2003), “Cell cycle and cell fate interactions in neural development.” Curr Opin Neurobiol 13(1):26-33 Details Vernon AE, Devine C, Philpott A (2003), “ The cdk inhibitor p27Xic1 is required for differentiation of primary neurones in Xenopus” Development, 130:85-92 Vernon AE, Devine C, Philpott A (2003), “The cdk inhibitor p27Xic1 is required for differentiation of primary neurones in Xenopus.” Development 130(1):85-92 Details Vernon AE, Philpott A (2003), “The developmental expression of cell cycle regulators in Xenopus laevis.” Gene Expr Patterns 3(2):179-92 Details Vernon AE, Philpott A (2003), “A single cdk inhibitor, p27Xic1, functions beyond cell cycle regulation to promote muscle differentiation in Xenopus.” Development 130(1):71-83 Details 2002Cossins J, Vernon AE, Zhang Y, Philpott A, Jones PH (2002), “Hes6 regulates myogenic differentiation.” Development 129(9):2195-207 Details Ohnuma S, Hopper S, Wang KC, Philpott A, Harris WA (2002), “Co-ordinating retinal histogenesis: early cell cycle exit enhances early cell fate determination in the Xenopus retina.” Development 129(10):2435-46 Details Richard-Parpaillon L, Héligon C, Chesnel F, Boujard D, Philpott A (2002), “The IGF pathway regulates head formation by inhibiting Wnt signaling in Xenopus.” Dev Biol 244(2):407-17 Details 2001Lücke CD, Philpott A, Metcalfe JC, Thompson AM, Hughes-Davies L, Kemp PR, Hesketh R (2001), “Inhibiting mutations in the transforming growth factor beta type 2 receptor in recurrent human breast cancer.” Cancer Res 61(2):482-5 Details Ohnuma S, Philpott A, Harris WA (2001), “Cell cycle and cell fate in the nervous system.” Curr Opin Neurobiol 11(1):66-73 Details 2000Philpott A, Krude T, Laskey RA (2000), “Nuclear chaperones.” Semin Cell Dev Biol 11(1):7-14 Details 1999Ohnuma S, Philpott A, Wang K, Holt CE, Harris WA (1999), “p27Xic1, a Cdk inhibitor, promotes the determination of glial cells in Xenopus retina.” Cell 99(5):499-510 Details Philpott A, Tsai L, Kirschner MW (1999), “Neuronal differentiation and patterning in Xenopus: the role of cdk5 and a novel activator xp35.2.” Dev Biol 207(1):119-32 Details Zuber ME, Perron M, Philpott A, Bang A, Harris WA (1999), “Giant eyes in Xenopus laevis by overexpression of XOptx2.” Cell 98(3):341-52 Details 1997Crevel G, Huikeshoven H, Cotterill S, Simon M, Wall J, Philpott A, Laskey RA, McConnell M, Fisher PA, Berrios M (1997), “Molecular and cellular characterization of CRP1, a Drosophila chromatin decondensation protein.” J Struct Biol 118(1):9-22 Details Philpott A, Porro EB, Kirschner MW, Tsai LH (1997), “The role of cyclin-dependent kinase 5 and a novel regulatory subunit in regulating muscle differentiation and patterning.” Genes Dev 11(11):1409-21 Details 1996Leno GH, Mills AD, Philpott A, Laskey RA (1996), “Hyperphosphorylation of nucleoplasmin facilitates Xenopus sperm decondensation at fertilization.” J Biol Chem 271(13):7253-6 Details 1994Kawasaki K, Philpott A, Avilion AA, Berrios M, Fisher PA (1994), “Chromatin decondensation in Drosophila embryo extracts.” J Biol Chem 269(13):10169-76 Details Philpott A, Friend SH (1994), “E2F and its developmental regulation in Xenopus laevis.” Mol Cell Biol 14(7):5000-9 Details 1993Laskey RA, Mills AD, Philpott A, Leno GH, Dilworth SM, Dingwall C (1993), “The role of nucleoplasmin in chromatin assembly and disassembly.” Philos Trans R Soc Lond B Biol Sci 339(1289):263-9; discussion 268-9 Details 1992Philpott A, Leno GH (1992), “Nucleoplasmin remodels sperm chromatin in Xenopus egg extracts.” Cell 69(5):759-67 Details 1991Laskey RA, Cox LS, Leno GH, Philpott A, Mills AD, Sleeman AM (1991), “Control of DNA replication in reconstituted nuclei.” Cold Spring Harb Symp Quant Biol 56:347-52 Details Philpott A, Leno GH, Laskey RA (1991), “Sperm decondensation in Xenopus egg cytoplasm is mediated by nucleoplasmin.” Cell 65(4):569-78 Details |