Professor Andrew Furley
School of Biosciences
Professor of Developmental Neuroscience, Deputy Head of School,
+44 114 222 2354
Full contact details
School of Biosciences
D18a
Firth Court
Western Bank
Sheffield
S10 2TN
- Profile
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- 2021-Present: Deputy Head of School, School of Biosciences, University of Sheffield
- 2018-2021: Professor of Developmental Neuroscience, School of Biosciences, University of Sheffield. Head of Research Training Faculty of Science
- 2004-2018: Senior Lecturer, Biomedical Science, University of Sheffield. Head of Research Training, Faculty of Science
- 1997-2004: Lecturer (Centre for Developmental & Biomedical Genetics), Biomedical Science, University of Sheffield
- 1992-1997: MRC Research Scientist, Division of Developmental Neurobiology, NIMR, Mill Hill, London
- 1990-1992: Howard Hughes Medical Institute Fellow, Center for Neurobiology & Behavior, Columbia University, New York (Advisor: T. Jessell)
- 1987-1990: Jane Coffin Childs Post-Doctoral Fellow, Dept of Biochemistry, Columbia University, New York (Advisors:F. Alt/T. Jessell)
- 1987: PhD Leukaemia Biology, Imperial Cancer Research/UCL, London (Supervisor: M. Greaves)
- 1982: B.Sc. (Hons) Molecular Biology, University of Edinburgh
- Research interests
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Our research is focussed on the role L1CAM-like cell adhesion molecules (L1-CNTNs) in neural development and disease (Gennarini et al., 2017; Gennarini & Furley., 2017). L1-CNTNs affect neural function at all stages, including the earliest proliferation and differentiation of progenitor and stem cells (Bizzoca et al 2003; Ma et al 2008; Xenaki et al., 2011; Bizzoca et al., 2012; Ha et al., 2015), the guidance of axons (Cohen et al 1998; Law et al 2008; Dang et al 2012), through to firing of action potentials (Poliak et al 2003) and functioning of synapses (Bliss et al 2000). As a result, these molecules are widely implicated in neurological disease and cancers.
Our aim is to understand the cellular mechanisms through which L1-CNTNs affect this wide variety of processes. Our current work is focussed particularly on the role of NrCAM in regulating the Sonic Hedgehog (SHH) pathway in medulloblastoma (Sakurai et al., 2001; Xenaki et al., 2011) and in neural stem cells (Bizzoca et al., 2012), with a specific emphasis on its role in controlling the trafficking of SHH pathway components into and out of primary cilia (Basu et al., 2015).
Most recently, we have begun to use neural organoids derived from human induced pluripotent cells (iPSCs) to develop in vitro systems with which to study both L1-CNTN function and to generate hypothalamic progenitors and neurons (with Barbaric and Placzek in BMS).
The cell biology of signal modulation in neural development and cancer
In biology context is everything. We aim to understand how cellular context alters the responses of cells to intercellular signals, focussing on the role of the L1-contactin ‘adhesion’ molecules (L1-CNTNs) in neural development. We have shown L1-CNTNs to modulate signals as diverse as semaphorins and hedgehogs (HHs) by altering the intracellular trafficking of their receptors during signalling. Our work on L1-CNTN modulation of Sema signalling during the wiring of mouse spinal sensory circuits (Dang et al 2012) has converged on our studies showing F3/contactin repression of Sonic HH-stimulated proliferation of cerebellar neuron progenitors (Xenaki et al 2011) to focus on a potential role for NrCAM in the trafficking of SHH signalling pathway components in the primary cilium. We are collaborating with Cadby (Physics) to develop STORM super resolution microscopy to follow this in real time (Peedikakkal et al., 2017). Collaborations with Clifford (Newcastle) reveal NrCAM to be upregulated in SHH group medulloblastomas and loss of NrCAM in vivo affects the penetrance of neoplasia in the Ptch1 mouse medulloblastoma model (Basu et al., 2015).
Roles for NrCAM in hypothalamic stem cell behaviour and for TAG1 in autism and obesity (3) are also being investigated with Placzek (BMS), Markx (NY) and Buchner (Ohio; Buchner et al 2012) respectively, while with Whyte, Walmsley (Edinburgh) and Renshaw (IICD/Bateson) we have investigated semaphorins in neutrophil function (Plant et al., 2020).
I also have a particular interest in the use of animals in research, which relates to my masters Bioethics teaching (with Townend, Maastricht), and was the Sheffield lead in an FP7 project (ANIMPACT) aimed at evaluating the impact of Directive 2010/63/EU on animal welfare and research competitiveness in member states (Fernandes et al., 2019).
- Publications
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Show: Featured publications All publications
Featured publications
Journal articles
- Neural cell adhesion molecule (NCAM-1) is required for ventricular conduction system development.. Development, 148(11).
- Excitatory granule neuron precursors orchestrate laminar localization and differentiation of cerebellar inhibitory interneuron subtypes. Cell Reports, 34(13).
- Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal. PLOS Biology, 18(3). View this article in WRRO
- Semaphorin 3F signaling actively retains neutrophils at sites of inflammation. Journal of Clinical Investigation. View this article in WRRO
- Methodological standards, quality of reporting, and regulatory compliance in animal research on amyotrophic lateral sclerosis: a systematic review. BMJ Open Science, 3(1). View this article in WRRO
- Cell adhesion molecules in neural development and disease. Molecular and Cellular Neuroscience, 81, 1-3. View this article in WRRO
- The role of Gpi-anchored axonal glycoproteins in neural development and neurological disorders. Molecular and Cellular Neuroscience, 81, 49-63. View this article in WRRO
- A forward genetic screen in mice identifies mutants with abnormal cortical patterning.. Cereb Cortex, 25(1), 167-179. View this article in WRRO
- Distinct Cis Regulatory Elements Govern the Expression of TAG1 in Embryonic Sensory Ganglia and Spinal Cord. PLoS ONE, 8, e57960-e57960. View this article in WRRO
- TAG1 regulates the endocytic trafficking and signaling of the semaphorin3A receptor complex.. J Neurosci, 32(30), 10370-10382. View this article in WRRO
- The juxtaparanodal proteins CNTNAP2 and TAG1 regulate diet-induced obesity.. Mamm Genome, 23(7-8), 431-442.
- F3/contactin and TAG1 play antagonistic roles in the regulation of sonic hedgehog-induced cerebellar granule neuron progenitor proliferation.. Development, 138(3), 519-529.
- The neural adhesion molecule TAG-1 modulates responses of sensory axons to diffusible guidance signals.. Development, 135(14), 2361-2371.
- A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis.. Nat Cell Biol, 10(3), 283-294.
- Loss of Function of the Neural Cell Adhesion Molecule NrCAM Regulates Differentiation, Proliferation and Neurogenesis in Early Postnatal Hypothalamic Tanycytes. Frontiers in Neuroscience, 16.
Conference proceedings papers
- TAG-1 regulates sensory axonal responses to the chemorepellant Semaphorin3A. MECHANISMS OF DEVELOPMENT, Vol. 126 (pp S306-S306)
All publications
Journal articles
- Neural cell adhesion molecule (NCAM-1) is required for ventricular conduction system development.. Development, 148(11).
- Excitatory granule neuron precursors orchestrate laminar localization and differentiation of cerebellar inhibitory interneuron subtypes. Cell Reports, 34(13).
- Crumbs2 mediates ventricular layer remodelling to form the spinal cord central canal. PLOS Biology, 18(3). View this article in WRRO
- Semaphorin 3F signaling actively retains neutrophils at sites of inflammation. Journal of Clinical Investigation. View this article in WRRO
- Methodological standards, quality of reporting, and regulatory compliance in animal research on amyotrophic lateral sclerosis: a systematic review. BMJ Open Science, 3(1). View this article in WRRO
- Development of targeted STORM for super resolution imaging of biological samples using digital micro-mirror device. Optics Communications, 404, 18-22. View this article in WRRO
- Cell adhesion molecules in neural development and disease. Molecular and Cellular Neuroscience, 81, 1-3. View this article in WRRO
- The role of Gpi-anchored axonal glycoproteins in neural development and neurological disorders. Molecular and Cellular Neuroscience, 81, 49-63. View this article in WRRO
- A forward genetic screen in mice identifies mutants with abnormal cortical patterning.. Cereb Cortex, 25(1), 167-179. View this article in WRRO
- Distinct Cis Regulatory Elements Govern the Expression of TAG1 in Embryonic Sensory Ganglia and Spinal Cord. PLoS ONE, 8, e57960-e57960. View this article in WRRO
- TAG1 regulates the endocytic trafficking and signaling of the semaphorin3A receptor complex.. J Neurosci, 32(30), 10370-10382. View this article in WRRO
- The juxtaparanodal proteins CNTNAP2 and TAG1 regulate diet-induced obesity.. Mamm Genome, 23(7-8), 431-442.
- F3/Contactin acts as a modulator of neurogenesis during cerebral cortex development. Developmental Biology, 365(1), 133-151.
- F3/contactin and TAG1 play antagonistic roles in the regulation of sonic hedgehog-induced cerebellar granule neuron progenitor proliferation.. Development, 138(3), 519-529.
- The neural adhesion molecule TAG-1 modulates responses of sensory axons to diffusible guidance signals.. Development, 135(14), 2361-2371.
- A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis (vol 10, pg 283, 2008). NAT CELL BIOL, 10(4), 497-497.
- A TAG1-APP signalling pathway through Fe65 negatively modulates neurogenesis.. Nat Cell Biol, 10(3), 283-294.
- Transgenic mice expressing F3/contactin from the transient axonal glycoprotein promoter undergo developmentally regulated deficits of the cerebellar function.. Neuroscience, 123(1), 155-166.
- Juxtaparanodal clustering of Shaker-like K+ channels in myelinated axons depends on Caspr2 and TAG-1.. J Cell Biol, 162(6), 1149-1160. View this article in WRRO
- Transgenic mice expressing F3/contactin from the TAG-1 promoter exhibit developmentally regulated changes in the differentiation of cerebellar neurons.. Development, 130(1), 29-43.
- Complete rescue of the nude mutant phenotype by a wild-type Foxn1 transgene.. Mamm Genome, 13(5), 245-252.
- . Genome Biology, 3(3), interactions2001.1-interactions2001.1.
- The trappist's approach to pathfinding: elucidating brain wiring using secretory-trap mutagenesis. Genome biology, 3(3), interactions2001.1-interactions2001.1.
- Overlapping functions of the cell adhesion molecules Nr-CAM and L1 in cerebellar granule cell development (vol 154, pg 1259, 2001). JOURNAL OF CELL BIOLOGY, 155(2), 311-311.
- Thyroid hormone regulates TAG-1 expression in the developing rat brain.. Eur J Neurosci, 14(8), 1209-1218.
- Overlapping functions of the cell adhesion molecules Nr-CAM and L1 in cerebellar granule cell development.. J Cell Biol, 154(6), 1259-1273. View this article in WRRO
- The trappist's approach to pathfinding: elucidating brain wiring using secretory-trap mutagenesis.. Genome Biol, 2(9), REVIEWS1026. View this article in WRRO
- Long-term potentiation in mice lacking the neural cell adhesion molecule L1.. Curr Biol, 10(24), 1607-1610.
- Regulation of the L1 cell adhesion molecule by thyroid hormone in the developing brain.. Mol Cell Neurosci, 16(4), 499-514.
- Molecular cloning and developmental expression of a zebrafish axonal glycoprotein similar to TAG-1.. Mech Dev, 80(2), 197-201.
- A functional interaction between the neuronal adhesion molecules TAG-1 and F3 modulates neurite outgrowth and fasciculation of cerebellar granule cells.. J Neurosci, 18(17), 6853-6870.
- Errors in corticospinal axon guidance in mice lacking the neural cell adhesion molecule L1.. Curr Biol, 8(1), 26-33.
- Cooperation of BMP7 and SHH in the induction of forebrain ventral midline cells by prechordal mesoderm.. Cell, 90(2), 257-269.
- Neural development: Patterning cascades in the neural tube. Current Biology, 6(5), 526-529. View this article in WRRO
- TAG-1 can mediate homophilic binding, but neurite outgrowth on TAG-1 requires an L1-like molecule and beta 1 integrins.. Neuron, 12(3), 675-690.
- Isolation of the cDNA and chromosomal localization of the gene (TAX1) encoding the human axonal glycoprotein TAG-1.. Genomics, 18(3), 562-567.
- Border disputes: do boundaries play a role in growth-cone guidance?. Trends Neurosci, 16(8), 316-323.
- The Role of the Immunoglobulin/Fibronectin Axonal Glycoprotein Subfamily in Axonal Fasciculation and Guidance.. Trends in Glycoscience and Glycotechnology, 3(13), 360-369.
- The axonal glycoprotein TAG-1 is an immunoglobulin superfamily member with neurite outgrowth-promoting activity.. Cell, 61(1), 157-170.
- Separate elements control DJ and VDJ rearrangement in a transgenic recombination substrate.. EMBO J, 9(1), 117-125.
- Control of VDJ recombinase activity.. Cold Spring Harb Symp Quant Biol, 54 Pt 1, 191-202.
- Phenotypic and genotypic analysis of two cell lines derived from Hodgkin's disease tissue biopsies.. Recent Results Cancer Res, 117, 62-66.
- The scid defect affects the final step of the immunoglobulin VDJ recombinase mechanism.. Cell, 54(4), 453-460.
- Cell lineage specificity of chromatin configuration around the immunoglobulin heavy chain enhancer.. EMBO J, 7(8), 2393-2399.
- MYC FAMILY GENE-EXPRESSION DURING HUMAN THYMIC ONTOGENY. CLINICAL RESEARCH, 36(3), A573-A573.
- Control of recombination events during lymphocyte differentiation. Heavy chain variable region gene assembly and heavy chain class switching.. Ann N Y Acad Sci, 546, 9-24.
- Lineage specificity of rearrangement and expression of genes encoding the T cell receptor-T3 complex and immunoglobulin heavy chain in leukemia.. Leukemia, 1(9), 644-652.
- Cloning of human thymic subcapsular cortex epithelial cells with SV40 origene.. Acta Paediatr Jpn, 29(4), 539-541.
- Cloning of human thymic subcapsular cortex epithelial cells with T-lymphocyte binding sites and hemopoietic growth factor activity.. Proc Natl Acad Sci U S A, 84(14), 4999-5003.
- Distribution and epitope analysis of the cell membrane glycoprotein (HPCA-1) associated with human hemopoietic progenitor cells.. Leukemia, 1(5), 417-426.
- Functional analysis of a clonal expansion of Leu 11 positive NK active lymphoid cells.. Br J Haematol, 65(3), 277-287.
- Cloning of Human Thymic Subcapsular Cortex Epithelial Cells with SV40 Ori-Gene. Pediatrics International, 29(4), 539-541.
- Inappropriate rearrangement of immunoglobulin and T-cell receptor genes. Immunology Today, 8(4), 115-116.
- Involvement of the D segment (DQ52) nearest to the JH region in immunoglobulin gene rearrangements of lymphoid-cell precursors.. Haematol Blood Transfus, 31, 320-323.
- Inappropriate rearrangement of immunoglobulin and T-cell receptor genes. Trends in Immunology, 8(4), 115-116.
- Rearrangement of immunoglobulin heavy chain genes in human T leukaemic cells shows preferential utilization of the D segment (DQ52) nearest to the J region.. EMBO J, 5(13), 3467-3473.
- Divergent molecular phenotypes of KG1 and KG1a myeloid cell lines. Blood, 68(5), 1101-1107.
- Divergent molecular phenotypes of KG1 and KG1a myeloid cell lines.. Blood, 68(5), 1101-1107.
- Differentiation-linked gene rearrangement and expression in acute lymphoblastic leukaemia.. Clin Haematol, 15(3), 621-639.
- Developmentally regulated rearrangement and expression of genes encoding the T cell receptor-T3 complex.. Cell, 46(1), 75-87.
- Clonal rearrangement and expression of the T cell receptor beta gene and involvement of the breakpoint cluster region in blast crisis of CGL. Blood, 67(2), 533-536.
- Clonal rearrangement and expression of the T cell receptor beta gene and involvement of the breakpoint cluster region in blast crisis of CGL.. Blood, 67(2), 533-536.
- Lineage promiscuity in hemopoietic differentiation and leukemia. Blood, 67(1), 1-11.
- Lineage promiscuity in hemopoietic differentiation and leukemia.. Blood, 67(1), 1-11.
- Loss of Function of the Neural Cell Adhesion Molecule NrCAM Regulates Differentiation, Proliferation and Neurogenesis in Early Postnatal Hypothalamic Tanycytes. Frontiers in Neuroscience, 16.
Chapters
- Tracking Differential Endocytosis and Trafficking of Semaphorin Receptor Complexes in Responding Nerve Growth Cones In Terman J (Ed.), Semaphorin Signalling New York: Humana Press.
- TAG-1/Axonin-1 In Kreis T & Vale R (Ed.), Guidebook to the extracellular matrix and adhesion proteins A Sambrook and Tooze Publication at Oxford University Press
Conference proceedings papers
- T3 Sema3F is an autocrine neutrophil retention signal regulating neutrophil transit and effector functions in acute lung injury. Thorax, Vol. 73(Suppl_4). London, UK, 5 December 2018 - 7 December 2018. View this article in WRRO
- "Mind the method!" - A longitudinal assessment of methodological soundness and quality of reporting of als research on the sod1g93a mouse. MEDICINE, Vol. 95(10)
- NrCAM modulates sonic hedgehog signalling by controlling smoothened translocation in the cilium. Cilia, Vol. 4((Suppl 1)) (pp 35-35), 18 November 2015 - 21 November 2015. View this article in WRRO
- The mRNA exporter GLE1 is essential for embryonic development. FEBS Journal, Vol. 281(Suppl 1) (pp 644-645)
- TAG-1 regulates sensory axonal responses to the chemorepellant Semaphorin3A. MECHANISMS OF DEVELOPMENT, Vol. 126 (pp S306-S306)
- A tag on to the physiological functions of APP in neurogenesis. JOURNAL OF NEUROCHEMISTRY, Vol. 106 (pp 32-32)
- Target-derived nerve growth factor (NGF) regulating spinal sensory axon outgrowth to the embryonic mouse gut. GASTROENTEROLOGY, Vol. 130(4) (pp A255-A255)
- Pathfinding of spinal commissural axons: The role of immunoglobulin-like cell adhesion molecules. EUROPEAN JOURNAL OF NEUROSCIENCE, Vol. 12 (pp 276-276)
- Misexpression of the mouse F3 axonal glycoprotein under the transient axonal glycoprotein promoter results in a cerebellar phenotype in early development.. EUROPEAN JOURNAL OF NEUROSCIENCE, Vol. 12 (pp 275-275)
- Gait analysis for possible behavioral assessment of transgenic mice. FASEB J, Vol. 12(4) (pp A135-A135)
Preprints
- The neural cell adhesion molecule NrCAM regulates development of hypothalamic tanycytes, Cold Spring Harbor Laboratory.
- A Multimodal Adaptive Super-Resolution and Confocal Microscope, Cold Spring Harbor Laboratory.
- Research group
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External collaborators
- Prof. Steve Clifford, Newcastle
- Prof. Moira Whyte & Dr Sarah Walmsley, Edinburgh
- Prof. Gianfrano Gennarini, Bari, Italy
- Prof. David Townend, Maastricht, Netherlands
- Dr Sander Markx, Columbia, NY, USA
- Dr David Buchner, Case Western, Ohio, USA
- Dr Avihu Klar, Hebrew University, Israel
- Dr David Beier, Harvard Medical School, Boston, USA
Current Lab Members:
- Miss Bethany James (MRC DiMeN PhD Student; joint with Prof Marysia Placzek and Dr Ivana Barbaric)
- Grants
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- Brain Tumour Support across Yorkshire
- FP7
- HEFCE
- Teaching activities
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Undergraduate and postgraduate taught modules
Undergraduate
- BMS109-153 Neuroscience
- BMS243/249 Developmental Neurobiology
- BMS381 Developmental Neurobiology (Co-ordinator)
- BMS382 Stem Cell Biology
- Level 3 Practical and Dissertation Modules
- BMS404 Ethics, the Law and Public Awareness of Science (Co-ordinator)
Masters (MSc)
- BMS6054 - Ethics, the Law and Public Awareness of Science (Co-ordinator)
- BMS6318 Developmental Neurobiology (Co-ordinator)
- Professional activities and memberships
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- British Society for Developmental Biology (BSDB; www.bsdb.org) Committee member (1999-2005); Publications Secretary (2000-2005; http://www.bms.ed.ac.uk/services/webspace/bsdb/BSDBnewsold.htm
- MRC Advisory Board (MAB) 2002-2005
- Appointed adviser on genetics and biotechnology to EU-wide consortium (PRIVILEGED) determining the ethical and legal interests in privacy and data protection for research involving the use of genetic databases and bio-banks, 2007. www.privilegedproject.eu
- Chair: BNA Symposium, Edinburgh. April 2015
- Panel Member: Volkswagen Foundation DiSCUSS-Cancer Stem Cells, Hannover. Oct 2014
- 2016 - 2020: External Examiner UG & MSc Neuroscience Programme, King’s College, London
- 2019: Invited participant & organiser, Bioethics Workshop, University of Zurich
- 2016: Guest Editor, Molecular and Cellular Neuroscience, Special Issue on “Cell Adhesion Molecules in Development and Disease”
- 2015: Chair and co-organiser, International Symposium “Exploring Axonal Development And Connectivity” at British Neuroscience Association Conference, Edinburgh
- 2014: Invited attendance the Academy of Medical Science symposium on “Reproducibility and Reliability of Biomedical Science” (April 2014) at the Wellcome Trust
- 2014: Career Session for Early Career Neurobiologists and Neuroscientists, Cold Spring Harbor Symposium on Axon Guidance & Neural Plasticity
- 2013-2017: UK lead for FP7 ANIMPACT consortium: ‘An ethical, legal and practical perspective on the impact of a new regulatory framework for the scientific use of animals on research and innovation’