Professor Andrew Furley
Professor of Developmental Neuroscience
Room: D18a Firth Court
Brief career history
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.
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 (1) has converged on our studies showing F3/contactin repression of Sonic HH-stimulated proliferation of cerebellar neuron progenitors (2) 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. 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.
Roles for NrCAM in hypothalamic stem cell behaviour and for TAG1 in autism and obesity (3) are also being investigated with Placzek (Bateson), Markx (NY) and Buchner (Ohio) respectively, while with Whyte, Walmsley (Edinburgh) and Renshaw (Bateson) we are investigating semaphorins in neutrophil function.
I also have a particular interest in the use of animals in research, which relates to my masters Bioethics teaching (with Townend, Maastricht), and am 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.
Undergraduate and postgraduate taught modules
- 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.
Conference proceedings papers
- "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