Randall, Andrew - University of Exeter

个人简介

After a year’s post-doc in the Pharmacology Department of Birmingham University Medical School I was awarded a Lucille P Markey Fellowship to support a 3 year period of research in Prof Richard Tsien’s laboratory in the Molecular and Cellular Physiology Department at Stanford University. Here I worked on Ca2+ channel diversity and its functional consequences in the CNS. In 1994 I moved to Cambridge, UK to my first group leader position which was in the Medical Research Council’s (MRC Laboratory of Molecular Biology on the Addenbrooks hospital site. Following 4 years in Cambridge I moved to SmithKlineBeecham in Harlow, which two years later became GlaxoSmithKline. Here I held the role of Director of Neurophysiology. In 2006 I moved to Bristol University School of Medical Sciences where I set up the Applied Neurophysiology group an alliance between the large Pharmaceutical company Wyeth and the University of Bristol, this ran until the end of 2012, a period encompassing the merger between Wyeth and Pfizer. In October 2012 I took up my post at the new University of Exeter Medical School where I have performed my research since late 2013.

研究领域

In Neurological diseases which cause dementia, for example Alzheimer’s disease (AD) and frontotemporal dementia, functional deficits arise as a result of changes to the electrical activity that occurs in neuronal networks. In the latter stages of such diseases, there is substantial neuronal death which alters the integrity of the surviving network. Earlier on in the disease process, prior to large scale neuronal loss, changes to circuits also seems to arise that likely underlie the initial cognitive deficits, and may also subsequently contribute to neuronal loss. Prof. Randall and his colleagues are interested in both the nature of these changes to neuronal networks in disease and how they develop. To probe this they make various forms of neurophysiological recordings from brain areas and circuits known to be affected in dementia, for example the hippocampus, cortex and thalamus. They work closely with pharmaceutical companies who are pursuing the dementia therapies of the future and also collaborate with mathematicians who are interested in producing models of the complexities of CNS signalling. They are also interested in understanding how different classes of ion channel contribute to the electrical signalling of neurones and ultimately if and how this changes in disease. Prof. Randall describes his research career in electrophysiology and imaging in the video below, filmed at the Living Systems Institute Symposium 2016.

近期论文

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Booth CA, Witton J, Nowacki J, Tsaneva-Atanasova K, Jones MW, Randall AD, Brown JT (2016). Altered Intrinsic Pyramidal Neuron Properties and Pathway-Specific Synaptic Dysfunction Underlie Aberrant Hippocampal Network Function in a Mouse Model of Tauopathy. J Neurosci, 36(2), 350-363. Abstract. Author URL. Full text. Article has an altmetric score of 16 Ly R, Bouvier G, Szapiro G, Prosser HM, Randall AD, Kano M, Sakimura K, Isope P, Barbour B, Feltz A, et al (2016). Contribution of postsynaptic T-type calcium channels to parallel fibre-Purkinje cell synaptic responses. J Physiol, 594(4), 915-936. Abstract. Author URL. Article has an altmetric score of 1 Booth CA, Ridler T, Murray TK, Ward MA, de Groot E, Goodfellow M, Phillips KG, Randall AD, Brown JT (2016). Electrical and Network Neuronal Properties Are Preferentially Disrupted in Dorsal, But Not Ventral, Medial Entorhinal Cortex in a Mouse Model of Tauopathy. J Neurosci, 36(2), 312-324. Abstract. Author URL. Full text. Article has an altmetric score of 13 Telezhkin V, Schnell C, Yarova P, Yung S, Cope E, Hughes A, Thompson BA, Sanders P, Geater C, Hancock JM, et al (2016). Forced cell cycle exit and modulation of GABAA, CREB, and GSK3β signaling promote functional maturation of induced pluripotent stem cell-derived neurons. Am J Physiol Cell Physiol, 310(7), C520-C541. Abstract. Author URL. Article has an altmetric score of 4 Cao L, McDonnell A, Nitzsche A, Alexandrou A, Saintot PP, Loucif AJ, Brown AR, Young G, Mis M, Randall A, et al (2016). Pharmacological reversal of a pain phenotype in iPSC-derived sensory neurons and patients with inherited erythromelalgia. Sci Transl Med, 8(335). Abstract. Author URL. Article has an altmetric score of 51 Alexandrou AJ, Brown AR, Chapman ML, Estacion M, Turner J, Mis MA, Wilbrey A, Payne EC, Gutteridge A, Cox PJ, et al (2016). Subtype-Selective Small Molecule Inhibitors Reveal a Fundamental Role for Nav1.7 in Nociceptor Electrogenesis, Axonal Conduction and Presynaptic Release. PLoS One, 11(4). Abstract. Author URL. Full text. Article has an altmetric score of 4 Dawson N, Kurihara M, Thomson DM, Winchester CL, McVie A, Hedde JR, Randall AD, Shen S, Seymour PA, Hughes ZA, et al (2015). Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1. Transl Psychiatry, 5 Abstract. Author URL. Full text. Article has an altmetric score of 71 Tamagnini F, Novelia J, Kerrigan TL, Brown JT, Tsaneva-Atanasova KT, Randall AD (2015). Altered intrinsic excitability of hippocampal CA1 pyramidal neurons in aged PDAPP mice. Front. Cell. Neurosci., 9 Full text. Article has an altmetric score of 11 Witton J, Staniaszek L, Bartsch U, Randall AD, Jones MW, Brown JT (2015). Disrupted hippocampal sharp-wave ripple-associated spike dynamics in a transgenic mouse model of dementia. Journal of Physiology, In press Abstract. Full text. Mehrban N, Zhu B, Tamagnini F, Young FI, Wasmuth A, Hudson KL, Thomson AR, Birchall MA, Randall AD, Song B, et al (2015). Functionalized α-Helical Peptide Hydrogels for Neural Tissue Engineering. ACS Biomater Sci Eng, 1(6), 431-439. Abstract. Author URL. Article has an altmetric score of 1 Witton J, Padmashri R, Zinyuk LE, Popov VI, Kraev I, Line SJ, Jensen TP, Tedoldi A, Cummings DM, Tybulewicz VL, et al (2015). Hippocampal circuit dysfunction in the Tc1 mouse model of Down syndrome. Nat Neurosci, 18(9), 1291-1298. Abstract. Author URL. Full text. Article has an altmetric score of 51 Tamagnini F, Scullion S, Brown JT, Randall AD (2015). Intrinsic excitability changes induced by acute treatment of hippocampal CA1 pyramidal neurons with exogenous Amyloid β peptide. Hippocampus, 25(7), 786-797. Full text. Nistor PA, May PW, Tamagnini F, Randall AD, Caldwell MA (2015). Long-term culture of pluripotent stem-cell-derived human neurons on diamond--A substrate for neurodegeneration research and therapy. Biomaterials, 61, 139-149. Abstract. Author URL. Article has an altmetric score of 12 Kerrigan TL, Brown JT, Randall AD (2014). Characterization of altered intrinsic excitability in hippocampal CA1 pyramidal cells of the Aβ-overproducing PDAPP mouse. Neuropharmacology, 79, 515-524. Abstract. Author URL. Randall AD, Kurihara M, Brandon NJ, Brown JT (2014). Disrupted in schizophrenia 1 and synaptic function in the mammalian central nervous system. Eur J Neurosci, 39(7), 1068-1073. Abstract. Author URL. Article has an altmetric score of 1 Tamagnini F, Scullion S, Brown JT, Randall AD (2014). Low concentrations of the solvent dimethyl sulphoxide alter intrinsic excitability properties of cortical and hippocampal pyramidal cells. PLoS One, 9(3). Abstract. Author URL. Booth CA, Brown JT, Randall AD (2014). Neurophysiological modification of CA1 pyramidal neurons in a transgenic mouse expressing a truncated form of disrupted-in-schizophrenia 1. Eur J Neurosci, 39(7), 1074-1090. Abstract. Author URL. Article has an altmetric score of 2 Curtis DJ, Sood A, Phillips TJ, Leinster VH, Nishiguchi A, Coyle C, Lacharme-Lora L, Beaumont O, Kemp H, Goodall R, et al (2014). Secretions from placenta, after hypoxia/reoxygenation, can damage developing neurones of brain under experimental conditions. Exp Neurol, 261, 386-395. Abstract. Author URL. Article has an altmetric score of 1 Kerrigan TL, Randall AD (2013). A new player in the "synaptopathy" of Alzheimer's disease - arc/arg 3.1. Front Neurol, 4 Abstract. Author URL. Article has an altmetric score of 2 Corbett BF, Leiser SC, Ling H-P, Nagy R, Breysse N, Zhang X, Hazra A, Brown JT, Randall AD, Wood A, et al (2013). Sodium channel cleavage is associated with aberrant neuronal activity and cognitive deficits in a mouse model of Alzheimer’s disease. The Journal of neuroscience : the official journal of the Society for Neuroscience, 33, 7020-6. Abstract.