Dr Rick Livesey

Rick Livesey

University position

Reader

Dr Rick Livesey is pleased to consider applications from prospective PhD students.

Departments

Department of Biochemistry

Institutes

Wellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology

Email

rick@gurdon.cam.ac.uk

Home page

http://www.gurdon.cam.ac.uk/researc...

Research Themes

Cellular and Molecular Neuroscience

Developmental Neuroscience

Interests

During embryonic development, all of the neurons in the cerebral cortex, the executive and integrative centre of the mammalian brain, are generated from a complex population of multipotent stem and progenitor cells. We have developed methods for replaying human cortical development from pluripotent stem cells. We are using that system to study the molecular mechanisms controlling eurogenesis in human cortical development, and how these are coordinated to generate complex lineages in a fixed temporal order.

Building on that work, we have used stem cells from people with Down syndrome and from patients with familial Alzheimer’s disease to create cell culture models of Alzheimer’s disease pathogenesis in cortical neurons. We are using those models to carry out mechanistic studies of AD initiation and progression in human stem cell models, using genetic forms of dementia and AD.

Human stem cell-derived neural rosettes
Human stem cell-derived neural rosettes
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Research Focus

Keywords

stem cells

cerebral cortex

neurodegeneration

Alzheimer's disease

Clinical conditions

Alzheimer's disease

Dementia

Genetic disorders

Learning disabilities

Progressive supranuclear palsy

Equipment

Cell culture

Fluorescence microscopy

Human pluripotent stem cells

Human stem cell models of neurodegenerative disease

Immunohistochemistry

Whole cell patch clamp

Collaborators

Cambridge

Roger Barker

Andrea Brand

Hugh Robinson

James Rowe

Ben Simons

Maria Grazia Spillantini

United Kingdom

John Hardy

Associated News Items


Key publications

Subkhankulova T, Livesey FJ (2006), “Comparative evaluation of linear and exponential amplification techniques for expression profiling at the single cell level” Genome Biol 7:R18 Details

Sansom SN, Hebert JM, Thammongkol U, Smith J, Nisbet G, Surani MA, McConnell SK, Livesey FJ (2005), “Genomic characterisation of a Fgf-regulated gradient-based neocortical protomap” Development 132:3947-61 Details

Livesey FJ, Young TL, Cepko CL (2004), “An analysis of the gene expression program of mammalian neural progenitor cells” Proc Natl Acad Sci U S A 101:1374-9 Details

Publications

2013

Alsiö JM, Tarchini B, Cayouette M, Livesey FJ (2013), “Ikaros promotes early-born neuronal fates in the cerebral cortex.” Proc Natl Acad Sci U S A 110(8):E716-25 Details

Mi D, Carr CB, Georgala PA, Huang YT, Manuel MN, Jeanes E, Niisato E, Sansom SN, Livesey FJ, Theil T, Hasenpusch-Theil K, Simpson TI, Mason JO, Price DJ (2013), “Pax6 exerts regional control of cortical progenitor proliferation via direct repression of Cdk6 and hypophosphorylation of pRb.” Neuron 78(2):269-84 Details

Olsson B, Legros L, Guilhot F, Strömberg K, Smith J, Livesey FJ, Wilson DH, Zetterberg H, Blennow K (2013), “Imatinib treatment and Aβ42 in humans.” Alzheimers Dement Details

Saurat N, Andersson T, Vasistha NA, Molnár Z, Livesey FJ (2013), “Dicer is required for neural stem cell multipotency and lineage progression during cerebral cortex development.” Neural Dev 8:14 Details

Tuoc TC, Boretius S, Sansom SN, Pitulescu ME, Frahm J, Livesey FJ, Stoykova A (2013), “Chromatin regulation by BAF170 controls cerebral cortical size and thickness.” Dev Cell 25(3):256-69 Details

2012

Livesey FJ (2012), “Stem cell models of Alzheimer's disease and related neurological disorders.” Alzheimers Res Ther 4(5):44 Details

Livesey FJ (2012), “A potential link between obesity and neural stem cell dysfunction.” Nat Cell Biol 14(10):987-9 Details

Shi Y, Kirwan P, Livesey FJ (2012), “Directed differentiation of human pluripotent stem cells to cerebral cortex neurons and neural networks.” Nat Protoc 7(10):1836-46 Details

Shi Y, Kirwan P, Smith J, MacLean G, Orkin SH, Livesey FJ (2012), “A human stem cell model of early Alzheimer's disease pathology in Down syndrome.” Sci Transl Med 4(124):124ra29 Details

Shi Y, Kirwan P, Smith J, Robinson HP, Livesey FJ (2012), “Human cerebral cortex development from pluripotent stem cells to functional excitatory synapses.” Nat Neurosci 15(3):477-86, S1 Details

2011

Brand AH, Livesey FJ (2011), “Neural stem cell biology in vertebrates and invertebrates: more alike than different?” Neuron 70(4):719-29 Details

2010

Andersson T, Rahman S, Sansom SN, Alsiö JM, Kaneda M, Smith J, O'Carroll D, Tarakhovsky A, Livesey FJ (2010), “Reversible block of mouse neural stem cell differentiation in the absence of dicer and microRNAs.” PLoS One 5(10):e13453 Details

Pereira JD, Sansom SN, Smith J, Dobenecker MW, Tarakhovsky A, Livesey FJ (2010), “Ezh2, the histone methyltransferase of PRC2, regulates the balance between self-renewal and differentiation in the cerebral cortex.” Proc Natl Acad Sci U S A 107(36):15957-62 Details

Subkhankulova T, Yano K, Robinson HP, Livesey FJ (2010), “Grouping and classifying electrophysiologically-defined classes of neocortical neurons by single cell, whole-genome expression profiling.” Front Mol Neurosci 3:10 Details

2009

Codega P, Della Santina L, Gargini C, Bedolla DE, Subkhankulova T, Livesey FJ, Cervetto L, Torre V (2009), “Prolonged illumination up-regulates arrestin and two guanylate cyclase activating proteins: a novel mechanism for light adaptation.” J Physiol 587(Pt 11):2457-72 Details

Sansom SN, Griffiths DS, Faedo A, Kleinjan DJ, Ruan Y, Smith J, van Heyningen V, Rubenstein JL, Livesey FJ (2009), “The level of the transcription factor Pax6 is essential for controlling the balance between neural stem cell self-renewal and neurogenesis.” PLoS Genet 5(6):e1000511 Details

Sansom SN, Livesey FJ (2009), “Gradients in the brain: the control of the development of form and function in the cerebral cortex.” Cold Spring Harb Perspect Biol 1(2):a002519 Details

2008

Git A, Spiteri I, Blenkiron C, Dunning MJ, Pole JC, Chin SF, Wang Y, Smith J, Livesey FJ, Caldas C (2008), “PMC42, a breast progenitor cancer cell line, has normal-like mRNA and microRNA transcriptomes.” Breast Cancer Res 10(3):R54 Details

Subkhankulova T, Gilchrist MJ, Livesey FJ (2008), “Modelling and measuring single cell RNA expression levels find considerable transcriptional differences among phenotypically identical cells.” BMC Genomics 9:268 Details

2006

Cobb BS, Hertweck A, Smith J, O'Connor E, Graf D, Cook T, Smale ST, Sakaguchi S, Livesey FJ, Fisher AG, Merkenschlager M (2006), “A role for Dicer in immune regulation.” J Exp Med 203(11):2519-27 Details

Pance A, Livesey FJ, Jackson AP (2006), “A role for the transcriptional repressor REST in maintaining the phenotype of neurosecretory-deficient PC12 cells.” J Neurochem 99(5):1435-44 Details

Yano K, Subkhankulova T, Livesey FJ, Robinson HP (2006), “Electrophysiological and gene expression profiling of neuronal cell types in mammalian neocortex.” J Physiol 575(Pt 2):361-5 Details

2004

Kawasaki H, Crowley JC, Livesey FJ, Katz LC (2004), “Molecular organization of the ferret visual thalamus.” J Neurosci 24(44):9962-70 Details

Perry P, Sauer S, Billon N, Richardson WD, Spivakov M, Warnes G, Livesey FJ, Merkenschlager M, Fisher AG, Azuara V (2004), “A dynamic switch in the replication timing of key regulator genes in embryonic stem cells upon neural induction.” Cell Cycle 3(12):1645-50 Details

Robinson M, Parsons Perez MC, Tébar L, Palmer J, Patel A, Marks D, Sheasby A, De Felipe C, Coffin R, Livesey FJ, Hunt SP (2004), “FLRT3 is expressed in sensory neurons after peripheral nerve injury and regulates neurite outgrowth.” Mol Cell Neurosci 27(2):202-14 Details

2003

Dyer MA, Livesey FJ, Cepko CL, Oliver G (2003), “Prox1 function controls progenitor cell proliferation and horizontal cell genesis in the mammalian retina.” Nat Genet 34(1):53-8 Details

Livesey FJ (2003), “Strategies for microarray analysis of limiting amounts of RNA.” Brief Funct Genomic Proteomic 2(1):31-6 Details

2001

Livesey FJ, Cepko CL (2001), “Vertebrate neural cell-fate determination: lessons from the retina.” Nat Rev Neurosci 2(2):109-18 Details

2000

Livesey FJ, Furukawa T, Steffen MA, Church GM, Cepko CL (2000), “Microarray analysis of the transcriptional network controlled by the photoreceptor homeobox gene Crx.” Curr Biol 10(6):301-10 Details

1999

Livesey FJ (1999), “Netrins and netrin receptors.” Cell Mol Life Sci 56(1-2):62-8 Details

1998

Livesey FJ, Hunt SP (1998), “Differential display cloning of genes induced in regenerating neurons.” Methods 16(4):386-95 Details

1997

Livesey FJ, Hunt SP (1997), “Netrin and netrin receptor expression in the embryonic mammalian nervous system suggests roles in retinal, striatal, nigral, and cerebellar development.” Mol Cell Neurosci 8(6):417-29 Details

Livesey FJ, O'Brien JA, Li M, Smith AG, Murphy LJ, Hunt SP (1997), “A Schwann cell mitogen accompanying regeneration of motor neurons.” Nature 390(6660):614-8 Details

1996

Livesey FJ, Hunt SP (1996), “Identifying changes in gene expression in the nervous system: mRNA differential display.” Trends Neurosci 19(3):84-8 Details

1992

Livesey FJ, Fraher JP (1992), “Experimental traction injuries of cervical spinal nerve roots: a scanning EM study of rupture patterns in fresh tissue.” Neuropathol Appl Neurobiol 18(4):376-86 Details