Professor Andrea Brand FRS FMedSci University positionHerchel Smith Professor and Royal Society Research Professor Professor Andrea Brand FRS FMedSci is pleased to consider applications from prospective PhD students. DepartmentsDepartment of Physiology, Development and Neuroscience InstitutesWellcome Trust/Cancer Research UK Gurdon Institute of Cancer and Developmental Biology Home pagehttp://www.gurdon.cam.ac.uk/researc... Research ThemesInterestsUncovering the molecular mechanisms that control neural stem quiescence and reactivation is crucial for understanding tissue regeneration under normal and pathological conditions and in response to ageing. It is critical to learn not only how stem cell proliferation is induced but also how stem cells can return to a quiescent state, as uncontrolled stem cell division can lead to cancer. My lab combines cutting edge genetic and molecular approaches with advanced imaging to study the reactivation of neural stem cells in vivo. The questions we are addressing are: How do environmental signals influence neural stem cell behaviour? What are these signals and how are they received by the stem cell niche and transmitted to neural stem cells? What are the transcriptional and epigenetic changes in neural stem cells in the transition from quiescence to proliferation? How are neurons maintained in a differentiated state and what molecular changes lead to dedifferentiation and cancer? Research Focus
EquipmentConfocal microscopy Genome wide analysis Live imaging Single cell RNA seq Targeted DamID (TaDa) CollaboratorsNo collaborators listed Associated News Items
Key publicationsHakes AE, Brand AH. (2020), “Tailless/TLX reverts intermediate neural progenitors to stem cells driving tumourigenesis via repression of asense/ASCL1.” Elife. 2020 Feb 19;9. pii: e53377. doi: 10.7554/eLife.53377. PMID: 32073402 Otsuki L, Brand AH. (2020), “Quiescent Neural Stem Cells for Brain Repair and Regeneration: Lessons from Model Systems. ” Trends Neurosci. 2020 Apr;43(4):213-226. doi: 10.1016/j.tins.2020.02.002. PMID: 32209453 Hakes AE, Brand AH. (2019), “Neural stem cell dynamics: the development of brain tumours.” Curr Opin Cell Biol. 2019 Oct;60:131-138. doi: 10.1016/j.ceb.2019.06.001. Review. PMID: 31330360 Otsuki L, Brand AH. (2019), “Dorsal-Ventral Differences in Neural Stem Cell Quiescence Are Induced by p57KIP2/Dacapo.” Dev Cell. 2019 Apr 22;49(2):293-300.e3. doi: 10.1016/j.devcel.2019.02.015. PMID: 30905769 van den Ameele J, Brand AH. (2019), “Neural stem cell temporal patterning and brain tumour growth rely on oxidative phosphorylation.” Elife. 2019 Sep 12;8. pii: e47887. doi: 10.7554/eLife.47887. PMID: 31513013 van den Ameele J, Krautz R, Brand AH. (2019), “TaDa! Analysing cell type-specific chromatin in vivo with Targeted DamID.” Curr Opin Neurobiol. 2019 Jun;56:160-166. doi: 10.1016/j.conb.2019.01.021. Review. PMID: 30844670 Cheetham SW, Brand AH. (2018), “RNA-DamID reveals cell-type-specific binding of roX RNAs at chromatin-entry sites.” Nat Struct Mol Biol. 2018 Jan;25(1):109-114. doi: 10.1038/s41594-017-0006-4. PMID: 29323275 Cheetham SW, Gruhn WH, van den Ameele J, Krautz R, Southall TD, Kobayashi T, Surani MA, Brand AH. (2018), “Targeted DamID reveals differential binding of mammalian pluripotency factors.” Development. 2018 Oct 17;145(20). pii: dev170209. doi: 10.1242/dev.170209. Otsuki L, Brand AH. (2018), “Cell cycle heterogeneity directs the timing of neural stem cell activation from quiescence.” Science. 2018 Apr 6;360(6384):99-102. doi: 10.1126/science.aan8795. PMID: 29622651 Spéder P, Brand AH. (2018), “Systemic and local cues drive neural stem cell niche remodelling during neurogenesis in Drosophila.” Elife. 2018 Jan 4;7. pii: e30413. doi: 10.7554/eLife.30413. PMID: 29299997 Marshall OJ, Brand AH. (2017), “Chromatin state changes during neural development revealed by in vivo cell-type specific profiling.” Nat Commun. 2017 Dec 22;8(1):2271. doi: 10.1038/s41467-017-02385-4. PMID: 29273756 Marshall OJ, Southall TD, Cheetham SW, Brand AH. (2016), “Cell-type-specific profiling of protein-DNA interactions without cell isolation using targeted DamID with next-generation sequencing.” Nature Protoc. 11(9):1586-98. Marshall OJ, Brand AH. (2015), “damidseq_pipeline: an automated pipeline for processing DamID sequencing datasets.” Bioinformatics 31(20):3371-3. Southall TD, Davidson CM, Miller C, Carr A, Brand AH (2014), “Dedifferentiation of Neurons Precedes Tumor Formation in lola Mutants.” Dev Cell 28(6):685-96 Details Spéder P, Brand AH. (2014), “Gap junction proteins in the blood-brain barrier control nutrient-dependent reactivation of Drosophila neural stem cells.” Dev Cell. 30(3):309-21. Southall TD, Gold KS, Egger B, Davidson CM, Caygill EE, Marshall OJ, Brand AH (2013), “Cell-type-specific profiling of gene expression and chromatin binding without cell isolation: assaying RNA Pol II occupancy in neural stem cells.” Dev Cell 26(1):101-12 Details Chell JM, Brand AH (2010), “Nutrition-responsive glia control exit of neural stem cells from quiescence.” Cell 143(7):1161-73 Details Publications2019Aloia L, McKie MA, Vernaz G, Cordero-Espinoza L, Aleksieva N, van den Ameele J, Antonica F, Font-Cunill B, Raven A, Aiese Cigliano R, Belenguer G, Mort RL, Brand AH, Zernicka-Goetz M, Forbes SJ, Miska EA, Huch M. (2019), “Epigenetic remodelling licences adult cholangiocytes for organoid formation and liver regeneration.” Nat Cell Biol. 2019 Nov;21(11):1321-1333. doi: 10.1038/s41556-019-0402-6. PMID: 31685987 Gervais L, van den Beek M, Josserand M, Sallé J, Stefanutti M, Perdigoto CN, Skorski P, Mazouni K, Marshall OJ, Brand AH, Schweisguth F, Bardin AJ. (2019), “Stem Cell Proliferation Is Kept in Check by the Chromatin Regulators Kismet/CHD7/CHD8 and Trr/MLL3/4.” Dev Cell. 2019 May 20;49(4):556-573.e6. doi: 10.1016/j.devcel.2019.04.033. PMID: 31112698 Jörg DJ, Caygill EE, Hakes AE, Contreras EG, Brand AH, Simons BD. (2019), “The proneural wave in the Drosophila optic lobe is driven by an excitable reaction-diffusion mechanism.” Elife. 2019 Feb 22;8. pii: e40919. doi: 10.7554/eLife.40919. PMID: 30794154 2018Contreras EG, Egger B, Gold KS, Brand AH. (2018), “Dynamic Notch signalling regulates neural stem cell state progression in the Drosophila optic lobe.” Neural Dev. 2018 Nov 22;13(1):25. doi: 10.1186/s13064-018-0123-8. PMID: 30466475 Contreras EG, Palominos T, Glavic Á, Brand AH, Sierralta J, Oliva C. (2018), “The transcription factor SoxD controls neuronal guidance in the Drosophila visual system.” Sci Rep. 2018 Sep 6;8(1):13332. doi: 10.1038/s41598-018-31654-5. PMID: 30190506 Doupé DP, Marshall OJ, Dayton H, Brand AH, Perrimon N. (2018), “Drosophila intestinal stem and progenitor cells are major sources and regulators of homeostatic niche signals.” Proc Natl Acad Sci U S A. 2018 Nov 27;115(48):12218-12223. doi: 10.1073/pnas.1719169115. Epub 2018 Nov 7. PMID: 30404917 Hakes AE, Otsuki L, Brand AH. (2018), “A newly discovered neural stem cell population is generated by the optic lobe neuroepithelium during embryogenesis in Drosophila melanogaster.” Development. 2018 Sep 25;145(18). pii: dev166207. doi: 10.1242/dev.166207. 2017Caygill EE, Brand AH. (2017), “miR-7 Buffers Differentiation in the Developing Drosophila Visual System.” Cell Rep. 20(6):1255-1261. Otsuki L, Brand AH. (2017), “The vasculature as a neural stem cell niche.” Neurobiol Dis. 107:4-14. 2016Cattenoz PB, Popkova A, Southall TD, Aiello G, Brand AH, Giangrande A. (2016), “Functional Conservation of the Glide/Gcm Regulatory Network Controlling Glia, Hemocyte, and Tendon Cell Differentiation in Drosophila.” Genetics 202(1):191-219. Caygill EE, Brand AH. (2016), “The GAL4 System: A Versatile System for the Manipulation and Analysis of Gene Expression.” Methods Mol Biol. 1478:33-52. 2014Gold KS, Brand AH. (2014), “Optix defines a neuroepithelial compartment in the optic lobe of the Drosophila brain.” Neural Dev. 9:18. Korzelius J, Naumann SK, Loza-Coll MA, Chan JS, Dutta D, Oberheim J, Gläßer C, Southall TD, Brand AH, Jones DL, Edgar BA. (2014), “Escargot maintains stemness and suppresses differentiation in Drosophila intestinal stem cells.” EMBO J. 33(24):2967-82. Liu J, Spéder P, Brand AH. (2014), “Control of brain development and homeostasis by local and systemic insulin signalling.” Diabetes Obes Metab. 16 Suppl 1:16-20. Loza-Coll MA, Southall TD, Sandall SL, Brand AH, Jones DL. (2014), “Regulation of Drosophila intestinal stem cell maintenance and differentiation by the transcription factor Escargot.” EMBO J. 33(24):2983-96. Neville MC, Nojima T, Ashley E, Parker DJ, Walker J, Southall T, Van de Sande B, Marques AC, Fischer B, Brand AH, Russell S, Ritchie MG, Aerts S, Goodwin SF (2014), “Male-specific fruitless isoforms target neurodevelopmental genes to specify a sexually dimorphic nervous system.” Curr Biol 24(3):229-41 Details Otsuki L, Cheetham SW, Brand AH. (2014), “Freedom of expression: cell-type-specific gene profiling.” Wiley Interdiscip Rev Dev Biol. 3(6):429-43. Wolfram V, Southall TD, Günay C, Prinz AA, Brand AH, Baines RA (2014), “The transcription factors islet and Lim3 combinatorially regulate ion channel gene expression.” J Neurosci 34(7):2538-43 Details 2013Cheetham SW, Brand AH (2013), “Cell biology. Insulin finds its niche.” Science 340(6134):817-8 Details 2012Gold KS, Brand AH (2012), “Transcriptome analysis of Drosophila neural stem cells.” Methods Mol Biol 916:99-110 Details Murray MJ, Southall TD, Liu W, Fraval H, Lorensuhewa N, Brand AH, Saint R (2012), “Snail-dependent repression of the RhoGEF pebble is required for gastrulation consistency in Drosophila melanogaster.” Dev Genes Evol 222(6):361-8 Details Wolfram V, Southall TD, Brand AH, Baines RA (2012), “The LIM-homeodomain protein islet dictates motor neuron electrical properties by regulating K(+) channel expression.” Neuron 75(4):663-74 Details 2011Brand AH, Livesey FJ (2011), “Neural stem cell biology in vertebrates and invertebrates: more alike than different?” Neuron 70(4):719-29 Details Egger B, Gold KS, Brand AH (2011), “Regulating the balance between symmetric and asymmetric stem cell division in the developing brain.” Fly (Austin) 5(3):237-41 Details Franco M, Seyfried NT, Brand AH, Peng J, Mayor U (2011), “A novel strategy to isolate ubiquitin conjugates reveals wide role for ubiquitination during neural development.” Mol Cell Proteomics 10(5):M110.002188 Details Spéder P, Liu J, Brand AH (2011), “Nutrient control of neural stem cells.” Curr Opin Cell Biol 23(6):724-9 Details 2010Bardin AJ, Perdigoto CN, Southall TD, Brand AH, Schweisguth F (2010), “Transcriptional control of stem cell maintenance in the Drosophila intestine.” Development 137(5):705-14 Details Egger B, Gold KS, Brand AH (2010), “Notch regulates the switch from symmetric to asymmetric neural stem cell division in the Drosophila optic lobe.” Development 137(18):2981-7 Details Monier B, Pélissier-Monier A, Brand AH, Sanson B (2010), “An actomyosin-based barrier inhibits cell mixing at compartmental boundaries in Drosophila embryos.” Nat Cell Biol 12(1):60-5; sup pp 1-9 Details 2009Hensch TK, Brand AH (2009), “Development. Editorial overview.” Curr Opin Neurobiol 19(2):109-11 Details Ruiz i Altaba A, Brand AH (2009), “Entity versus property: tracking the nature, genesis and role of stem cells in cancer. Conference on Stem cells and cancer.” EMBO Rep 10(8):832-6 Details Southall TD, Brand AH (2009), “Neural stem cell transcriptional networks highlight genes essential for nervous system development.” EMBO J 28(24):3799-807 Details von Trotha JW, Egger B, Brand AH (2009), “Cell proliferation in the Drosophila adult brain revealed by clonal analysis and bromodeoxyuridine labelling.” Neural Dev 4:9 Details 2008Brand AH (2008), “A new dawn for Aurora?” Nat Cell Biol 10(11):1253-4 Details Chell JM, Brand AH (2008), “Forever young: death-defying neuroblasts.” Cell 133(5):769-71 Details Egger B, Chell JM, Brand AH (2008), “Insights into neural stem cell biology from flies.” Philos Trans R Soc Lond B Biol Sci 363(1489):39-56 Details Elliott DA, Brand AH (2008), “The GAL4 system : a versatile system for the expression of genes.” Methods Mol Biol 420:79-95 Details Southall TD, Brand AH (2008), “Generation of Driver and Reporter Constructs for the GAL4 Expression System in Drosophila.” CSH Protoc 2008:pdb.prot5029 Details Southall TD, Egger B, Gold KS, Brand AH (2008), “Regulation of self-renewal and differentiation in the Drosophila nervous system.” Cold Spring Harb Symp Quant Biol 73:523-8 Details Southall TD, Elliott DA, Brand AH (2008), “The GAL4 System: A Versatile Toolkit for Gene Expression in Drosophila.” CSH Protoc 2008:pdb.top49 Details Wu PS, Egger B, Brand AH (2008), “Asymmetric stem cell division: lessons from Drosophila.” Semin Cell Dev Biol 19(3):283-93 Details 2007Edoff K, Dods JS, Brand AH (2007), “Detection of GFP during nervous system development in Drosophila melanogaster.” Methods Mol Biol 411:81-98 Details Egger B, Boone JQ, Stevens NR, Brand AH, Doe CQ (2007), “Regulation of spindle orientation and neural stem cell fate in the Drosophila optic lobe” Neural Development 2:1 Details Southall TD, Brand AH (2007), “Chromatin profiling in model organisms.” Brief Funct Genomic Proteomic 6(2):133-40 Details 2006Barbee SA, Estes PS, Cziko AM, Hillebrand J, Luedeman RA, Coller JM, Johnson N, Howlett IC, Geng C, Ueda R, Brand AH, Newbury SF, Wilhelm JE, Levine RB, Nakamura A, Parker R, Ramaswami M (2006), “Staufen- and FMRP-containing neuronal RNPs are structurally and functionally related to somatic P bodies.” Neuron 52(6):997-1009 Details Bossing T, Brand AH (2006), “Determination of cell fate along the anteroposterior axis of the Drosophila ventral midline.” Development 133(6):1001-12 Details Choksi SP, Southall T, Bossing T, Edoff K, de Wit E, van Steensel B, Micklem G, Brand AH (2006), “Prospero acts as a binary switch between self-renewal and differentiation in Drosophila neural stem cells” Developmental Cell 11:775-789 Details Murray MJ, Davidson CM, Hayward NM, Brand AH (2006), “The Fes/Fer non-receptor tyrosine kinase cooperates with Src42A to regulate dorsal closure in Drosophila.” Development 133(16):3063-73 Details Pym EC, Southall TD, Mee CJ, Brand AH, Baines RA (2006), “The homeobox transcription factor Even-skipped regulates acquisition of electrical properties in Drosophila neurons.” Neural Dev 1:3 Details 2005Dawes-Hoang RE, Parmar KM, Christiansen AE, Phelps CB, Brand AH, Wieschaus EF (2005), “folded gastrulation, cell shape change and the control of myosin localization.” Development 132(18):4165-78 Details 2004Carr AR, Choksi SP, Brand AH (2004), “Turning back the clock on neural progenitors.” Bioessays 26(7):711-4 Details van Roessel P, Brand AH (2004), “Spreading silence with Sid.” Genome Biol 5(2):208 Details van Roessel P, Elliott DA, Robinson IM, Prokop A, Brand AH (2004), “Independent regulation of synaptic size and activity by the anaphase-promoting complex.” Cell 119(5):707-18 Details van Roessel PJ, Elliott DA, Robinson IM, Prokop A, Brand AH (2004), “Independent regulation of synaptic size and activity by the anaphase-promoting complex” Cell 119:707-718 2003Barros CS, Phelps CB, Brand AH (2003), “Drosophila nonmuscle myosin II promotes the asymmetric segregation of cell fate determinants by cortical exclusion rather than active transport.” Dev Cell 5(6):829-40 Details Brand AH, van Roessel PJ (2003), “Region-specific apoptosis limits neural stem cell proliferation.” Neuron 37(2):185-7 Details 2002Bossing T, Barros CS, Brand AH (2002), “Rapid tissue-specific expression assay in living embryos.” Genesis 34(1-2):123-6 Details Bossing T, Brand AH (2002), “Dephrin, a transmembrane ephrin with a unique structure, prevents interneuronal axons from exiting the Drosophila embryonic CNS.” Development 129(18):4205-18 Details Januschke J, Gervais L, Dass S, Kaltschmidt JA, Lopez-Schier H, St Johnston D, Brand AH, Roth S, Guichet A (2002), “Polar transport in the Drosophila oocyte requires Dynein and Kinesin I cooperation.” Curr Biol 12(23):1971-81 Details Kaltschmidt JA, Brand AH (2002), “Asymmetric cell division: microtubule dynamics and spindle asymmetry.” J Cell Sci 115(Pt 11):2257-64 Details van Roessel P, Brand AH (2002), “Imaging into the future: visualizing gene expression and protein interactions with fluorescent proteins.” Nat Cell Biol 4(1):E15-20 Details Van Roessel P, Hayward NM, Barros CS, Brand AH (2002), “Two-color GFP imaging demonstrates cell-autonomy of GAL4-driven RNA interference in Drosophila.” Genesis 34(1-2):170-3 Details 2001Bellaďche Y, Gho M, Kaltschmidt JA, Brand AH, Schweisguth F (2001), “Frizzled regulates localization of cell-fate determinants and mitotic spindle rotation during asymmetric cell division.” Nat Cell Biol 3(1):50-7 Details 2000Kaltschmidt JA, Davidson CM, Brown NH, Brand AH (2000), “Rotation and asymmetry of the mitotic spindle direct asymmetric cell division in the developing central nervous system.” Nat Cell Biol 2(1):7-12 Details 1999Haseloff J, Dormand EL, Brand AH (1999), “Live imaging with green fluorescent protein.” Methods Mol Biol 122:241-59 Details Schuldt AJ, Brand AH (1999), “Mastermind acts downstream of notch to specify neuronal cell fates in the Drosophila central nervous system.” Dev Biol 205(2):287-95 Details 1998Dormand EL, Brand AH (1998), “Runt determines cell fates in the Drosophila embryonic CNS.” Development 125(9):1659-67 Details Murray MJ, Merritt DJ, Brand AH, Whitington PM (1998), “In vivo dynamics of axon pathfinding in the Drosophilia CNS: a time-lapse study of an identified motorneuron.” J Neurobiol 37(4):607-21 Details Phelps CB, Brand AH (1998), “Ectopic gene expression in Drosophila using GAL4 system.” Methods 14(4):367-79 Details Schuldt AJ, Adams JH, Davidson CM, Micklem DR, Haseloff J, St Johnston D, Brand AH (1998), “Miranda mediates asymmetric protein and RNA localization in the developing nervous system.” Genes Dev 12(12):1847-57 Details 1997Hidalgo A, Brand AH (1997), “Targeted neuronal ablation: the role of pioneer neurons in guidance and fasciculation in the CNS of Drosophila.” Development 124(17):3253-62 Details 1995Brand AH, Dormand EL (1995), “The GAL4 system as a tool for unravelling the mysteries of the Drosophila nervous system.” Curr Opin Neurobiol 5(5):572-8 Details Hidalgo A, Urban J, Brand AH (1995), “Targeted ablation of glia disrupts axon tract formation in the Drosophila CNS.” Development 121(11):3703-12 Details Yoffe KB, Manoukian AS, Wilder EL, Brand AH, Perrimon N (1995), “Evidence for engrailed-independent wingless autoregulation in Drosophila.” Dev Biol 170(2):636-50 Details 1994Brand AH, Manoukian AS, Perrimon N (1994), “Ectopic expression in Drosophila.” Methods Cell Biol 44:635-54 Details Brand AH, Perrimon N (1994), “Raf acts downstream of the EGF receptor to determine dorsoventral polarity during Drosophila oogenesis.” Genes Dev 8(5):629-39 Details Staehling-Hampton K, Jackson PD, Clark MJ, Brand AH, Hoffmann FM (1994), “Specificity of bone morphogenetic protein-related factors: cell fate and gene expression changes in Drosophila embryos induced by decapentaplegic but not 60A.” Cell Growth Differ 5(6):585-93 Details 1993Brand AH, Perrimon N (1993), “Targeted gene expression as a means of altering cell fates and generating dominant phenotypes.” Development 118(2):401-15 Details 1989Hofmann JF, Laroche T, Brand AH, Gasser SM (1989), “RAP-1 factor is necessary for DNA loop formation in vitro at the silent mating type locus HML.” Cell 57(5):725-37 Details 1987Brand AH, Micklem G, Nasmyth K (1987), “A yeast silencer contains sequences that can promote autonomous plasmid replication and transcriptional activation.” Cell 51(5):709-19 Details Shore D, Stillman DJ, Brand AH, Nasmyth KA (1987), “Identification of silencer binding proteins from yeast: possible roles in SIR control and DNA replication.” EMBO J 6(2):461-7 Details 1985Brand AH, Breeden L, Abraham J, Sternglanz R, Nasmyth K (1985), “Characterization of a "silencer" in yeast: a DNA sequence with properties opposite to those of a transcriptional enhancer.” Cell 41(1):41-8 Details |