Faculty of Biological Sciences

Dr Hugh Pearson

BSc, PhD 1990, London.
Senior Lecturer
School of Biomedical Sciences

Contact:  Garstang 6.41f, +44(0) 113 34 34815, email address for  

Research Interests

The role of voltage gated ion channels in Alzheimer's disease. Understanding brain function: calcium channel subtypes and their modulation in central neurones.

Cultured granule cells from the cerebellum being patch clamped

Cultured granule cells from the cerebellum being patch clamped.
Spherical or ovoid cell bodies have bipolar neurite (axon or dendrite) extensions.
The right hand pipette is the patch pipette and drugs are applied from the other two pipettes.

The role of voltage-gated ion channels in Alzheimer's disease.

Alzheimer's disease is becoming an increasing large clinical problem as the average age of our population gets higher. An estimated 5-10% of the population over the age of 65 develop Alzheimer's disease (AD) and this figure increases even further in more elderly age groups. A hallmark of AD is the loss of neurones in the cortex and memory forming areas of the brain such as the hippocampus. We have been studying the effects of an AD-related peptide, amyloid protein (Ab) on voltage-gated ion channel currents in cultured neurones using the whole-cell patch clamp technique (see publications below). The effects on ion channel currents have also been correlated with the Ab-induced cell death. To do this we use a variety of neurotoxicity assays, some biochemical such as the MTT, TUNEL or LDH release assays, and some morphological, where we fix and stain cells and look for changes in membrane and nuclear structure. In future we also plan to use flourescent assays to monitor cell death/survival following challenge with Ab. Related to this project are studies regarding the effect of free radicals on ion channel activity and cell survival. More recently we have begun to use brain tissue from patients undergoing operations to remove tumours to study Ca2+ handling and ion channel activity in human astrocytes.

Human astrocytes grown from biopsy tissue removed from a patient with an astroglioma. Stained with antibody directed against GFAP

Human astrocytes grown from biopsy tissue removed from a patient with an astroglioma.
Stained with antibody directed against GFAP.


Funding

Wellcome Trust
MRC - part of the MRC Neurodegeneration Co-operative group
Nuffield Foundation

Lab members

Leigh Plant, PhD Student
Magdy Omar, PhD Student
Nicola Webster, Postdoctoral Research Fellow
TBA, Postdoctoral Research Fellow

Working hard in La Jolla, California with PhD students Leigh Plant and Martin Ramsden

Working hard in La Jolla, California with PhD students Leigh Plant and Martin Ramsden

Collaborators

Zaineb Henderson, School of Biomedical Sciences
Paul Kemp, School of Biomedical Sciences
Les Bridges, Neuropathology, School of Medicine
Peter Vaughan, Cardiovascular Research, School of Medicine
Chris Peers, Cardiovascular Research, School of Medicine
Paul Chumas, Neurosurgery, School of Medicine

Veronica Campbell, Trinity College, Dublin
Richard Cowburn, Karolinska Institutet, Sweden

 

Faculty Research and Innovation



Studentship information

Postgraduate studentship areas:

  • Modulation of ion channels in Alzheimer's disease.

See also:

Modules managed

BMSC2118 - Neurobiology
BMSC2227 - Experimental Skills in Neuroscience
BMSC3398 - Practical Research Skills

Modules taught

BMSC1210 - Biology of the Mind
BMSC1213 - Basic Laboratory and Scientific Skills 2
BMSC1214 - Human Endocrinology
BMSC2118 - Neurobiology
BMSC2120 - Scientific Skills
BMSC2223 - Neuropharmacology
BMSC2223/BMSC3302 - Neuropharmacology/Medical Pharmacology
BMSC2227 - Experimental Skills in Neuroscience
BMSC3140 - Advanced Scientific Skills
BMSC3143/44/45/46/BIOC3111/12/BIOL3112 - ATU - Neurodegeneration
BMSC3233/34/35/36 - Advanced topics for BMS students II
BMSC3301 - Research Project in Biomedical Sciences
BMSC3398 - Practical Research Skills
BMSC3399 - Extended Research Project Preparation
MEDI2201 - Control and Movement

Centre membership: Neuroscience Research at Leeds (NeuR@L)

Group Leader Dr Hugh Pearson  (Senior Lecturer)

The role of voltage gated ion channels in Alzheimer's disease. Understanding brain function: calcium channel subtypes and their modulation in central neurones. 

Neelov IM, Janaszewska A, Klajnert B, Bryszewska M, Makova NZ, Hicks D, Pearson HA, Vlasov GP, Ilyash MY, Vasilev DS, Dubrovskaya NM, Tumanova NL, Zhuravin IA, Turner AJ, Nalivaeva NN Molecular properties of lysine dendrimers and their interactions with Aβ-peptides and neuronal cells. Curr Med Chem 20 134-143, 2013
View abstract

Hettiarachchi NT, Boyle JP, Bauer CC, Dallas ML, Pearson HA, Hara S, Gamper N, Peers C Peroxynitrite mediates disruption of Ca2+ homeostasis by carbon monoxide via Ca2+ ATPase degradation. Antioxid Redox Signal 17 744-755, 2012
DOI:10.1089/ars.2011.4398
View abstract

Boyle JP, Hettiarachchi NT, Wilkinson JA, Pearson HA, Scragg JL, Lendon C, Al-Owais MM, Kim CB, Myers DM, Warburton P, Peers C Cellular consequences of the expression of Alzheimer's disease-causing presenilin 1 mutations in human neuroblastoma (SH-SY5Y) cells. Brain Res 1443 75-88, 2012
DOI:10.1016/j.brainres.2011.12.061
View abstract

Dallas ML, Boyle JP, Milligan CJ, Sayer R, Kerrigan TL, McKinstry C, Lu P, Mankouri J, Harris M, Scragg JL, Pearson HA, Peers C Carbon monoxide protects against oxidant-induced apoptosis via inhibition of Kv2.1. FASEB J 25 1519-1530, 2011
DOI:10.1096/fj.10-173450
View abstract

Hettiarachchi NT, Dallas ML, Pearson HA, Bruce G, Deuchars S, Boyle JP, Peers C Gap junction-mediated spontaneous Ca(2+) waves in differentiated cholinergic SN56 cells. Biochem Biophys Res Commun 397 564-568, 2010
DOI:10.1016/j.bbrc.2010.05.159
View abstract

Hettiarachchi NT, Parker A, Dallas ML, Pennington K, Hung C-C, Pearson HA, Boyle JP, Robinson P, Peers C alpha-Synuclein modulation of Ca2+ signaling in human neuroblastoma (SH-SY5Y) cells. J Neurochem 111 1192-1201, 2009
DOI:10.1111/j.1471-4159.2009.06411.x
View abstract

Hettiarachchi NT, Parker A, Dallas ML, Pennington K, Hung CC, Pearson HA, Boyle JP, Robinson P, Peers C α-Synuclein modulation of Ca2+ signaling in human neuroblastoma (SH-SY5Y) cells Journal of Neurochemistry 111 1192-1201, 2009
DOI:10.1111/j.1471-4159.2009.06411.x
View abstract

Dallas ML, Boycott H, Miller A, Wilkinson J, Boyle J, Pearson HA, Peers C MONITORING CELL SURFACE EXPRESSION USING TRANSPORTER CURRENTS: FOCUS ON HYPOXIC MODULATION., 2009

Milligan CJ, Li J, Sukumar P, Majeed Y, Dallas ML, English A, Emery P, Porter KE, Smith AM, McFadzean I, Beccano-Kelly D, Bahnasi Y, Cheong A, Naylor J, Zeng FN, Liu X, Gamper N, Jiang LH, Pearson HA, Peers C, Robertson B, Beech DJ Robotic multiwell planar patch-clamp for native and primary mammalian cells NAT PROTOC 4 244-255, 2009
DOI:10.1038/nprot.2008.230

Peers C, Dallas ML, Boycott HE, Scragg JL, Pearson HA, Boyle JP Hypoxia and Neurodegeneration HYPOXIA AND CONSEQUENCES FROM MOLECULE TO MALADY 1177 169-177, 2009
DOI:10.1111/j.1749-6632.2009.05026.x

Boycott HE, Wilkinson JA, Boyle JP, Pearson HA, Peers C Differential involvement of TNF alpha in hypoxic suppression of astrocyte glutamate transporters GLIA 56 998-1004, 2008
DOI:10.1002/glia.20673

Kerrigan TL, Atkinson L, Peers C, Pearson HA Modulation of 'A'-type K+ current by rodent and human forms of amyloid beta protein NEUROREPORT 19 839-843, 2008

Boycott HE, Dallas M, Boyle JP, Pearson HA, Peers C Hypoxia suppresses astrocyte glutamate transport independently of amyloid formation BIOCHEM BIOPH RES CO 364 100-104, 2007
DOI:10.1016/j.bbrc.2007.09.102

Dallas M, Boycott HE, Atkinson L, Miller A, Boyle JP, Pearson HA, Peers C Hypoxia suppresses glutamate transport in astrocytes J NEUROSCI 27 3946-3955, 2007
DOI:10.1523/JNEUROSCI.5030-06.2007

Dallas ML, Boycott HE, Atkinson L, Miller A, Boyle JP, Pearson HA, Peers C Hypoxia suppresses glutamate transport in astrocytes Journal of Neuroscience 27 3946-3955, 2007
View abstract

Pearson HA Calcium channel subtypes - another layer of complexity to an already intricate story J PHYSIOL-LONDON 578 629-629, 2007
DOI:10.1113/jphysiol.2006.126144

Peers C, Pearson HA, Boyle JP Hypoxia and Alzheimer's disease ESSAYS BIOCHEM 43 153-164, 2007

Plant LD, Webster NJ, Boyle JP, Ramsden M, Freir DB, Peers C, Pearson HA Amyloid beta peptide as a physiological modulator of neuronal 'A'-type K+ current NEUROBIOL AGING 27 1673-1683, 2006
DOI:10.1016/j.neurobiolaging.2005.09.038

Pearson HA, Peers C Physiological roles for amyloid beta peptides J PHYSIOL-LONDON 575 5-10, 2006
DOI:10.1113/jphysiol.2006.111203

Atkinson L, Boyle JP, Pearson HA, Peers C Chronic hypoxia inhibits Na+/Ca2+ exchanger expression in cortical astrocytes NEUROREPORT 17 649-652, 2006

Webster NJ, Ramsden M, Boyle JP, Pearson HA, Peers C Amyloid peptides mediate hypoxic increase of L-type Ca2+ channels in central neurones NEUROBIOL AGING 27 439-445, 2006
DOI:10.1016/j.neurobiolaging.2005.02.002

Peers C, Aley PK, Boyle JP, Porter KE, Pearson HA, Smith IF, Kemp PJ Hypoxic regulation of Ca<sup>2+</sup> signalling in astrocytes and endothelial cells, 2006
DOI:10.1007/0-387-31311-7_28

Peers C, Aley PK, Boyle JP, Porter KE, Pearson HA, Smith IF, Kemp PJ Hypoxic regulation of Ca2+ signalling in astrocytes and endothelial cells ARTERIAL CHEMORECEPTORS 580 185-190, 2006
DOI:10.1007/0-387-31311-7_28

Peers C, Kang P, Boyle JP, Porter KE, Pearson HA, Smith IF, Kemp PJ Hypoxic regulation of Ca2+ signalling in astrocytes and endothelial cells. Novartis Found Symp 272 119-127, 2006
View abstract

Aley PK, Murray HJ, Boyle JP, Pearson HA, Peers C Hypoxia stimulates Ca2+ release from intracellular stores in astrocytes via cyclic ADP ribose-mediated activation of ryanodine receptors CELL CALCIUM 39 95-100, 2006
DOI:10.1016/j.ceca.2005.09.009

Peers C, Scragg JL, Boyle JP, Fearon IM, Taylor SC, Green KN, Webster NJ, Ramsden M, Pearson HA A central role for ROS in the functional remodelling of L-type Ca2+ channels by hypoxia PHILOS T ROY SOC B 360 2247-2254, 2005
View abstract

Peers C, Kang P, Boyle JP, Porter KE, Pearson HA, Smith IF, Kemp PJ Hypoxic regulation of Ca2+ signaling in astrocytes and endothelial cells In Novartis Foundation Symposium , 2005

Smith IF, Boyle JP, Kang P, Rome S, Pearson HA, Peers C Hypoxic regulation of Ca2+ signaling in cultured rat astrocytes GLIA 49 153-157, 2005
DOI:10.1002/glia.20083

Smith IF, Boyle JP, Green KN, Pearson HA, Peers C Hypoxic remodelling of Ca<sup>2+</sup>mobilization in type I cortical astrocytes: involvement of ROS and pro-amyloidogenic APP processing Journal of Neurochemistry 88 869-877, 2004

Peers C, Smith IF, Boyle JP, Pearson HA Remodelling of Ca2+ homeostasis in type I cortical astrocytes by hypoxia: evidence for association with Alzheimer's disease. Journal of Biological Chemistry 385 285-289, 2004
DOI:10.1515/BC.2004.023

Plant LD, Boyle JP, Smith IF, Peers C, Pearson HA The Production of Amyloid&beta; Peptide is a Critical Requirement for the Viability of Central Neurones Journal of Neuroscience 23 5531-5535, 2003
View abstract

Smith IF, Plant LD, Boyle JP, Skinner RA, Pearson HA, Peers C Chronic hypoxia potentiates capacitative Ca2+ entry in type I cortical astrocytes Journal of Neurochemistry 85 1109-1116, 2003
DOI:10.1046/j.1471-4159.2003.01785.x
View abstract

Peers C, Smith IF, Boyle JP, Pearson HA Hypoxic remodelling of Ca2+ homeostasis in rat type 1 cortical astrocytes In Advances in Experimental Medicine and Biology , 2003

Peers C, Lewis A, Plant LD, Pearson HA, Kemp PJ Oxygen-sensitive K+ channels controlling cell excitability In Lung Oxygen Sensing , 2003

Smith IF, Boyle JP, Plant LD, Pearson HA, Peers C Hypoxic remodeling of Ca2+ stores in type I cortical astrocytes Journal of Biological Chemistry 278 4875-4881, 2003
DOI:10.1074/jbc.M209206200
View abstract

Peers C, Lewis A, Plant LD, Pearson HA, Kemp PJ 02-sensitive K+ channels controlling cell excitability. In: Oxygen Sensing: Responses and Adaptations to Hypoxia In Oxygen Sensing- Responses and Adaptation to Hypoxia. , 2003

Ramsden M, Henderson Z, Pearson HA Modulation of Ca2+ channel currents in primary cultures of rat cortical neurones by amyloid beta protein (1-40) is dependent on solubility status. Brain Res 956 254-261, 2002
View abstract

Liversage RB, Plant LD, Pearson HA, Beech DJ, Bateson AN GABA(A) receptor activation increases [Ca2+]i via a nifedipine-sensitive pathway in cultured rat cerebellar granule neurones, 2002

Plant LD, Boyle JP, Peers C, Pearson HA Cell death following inhibition of amyloid beta protein production in primary cultures of rat central neurones, 2002

Plant LD, Webster NJ, Henderson Z, Peers C, Pearson HA Endogenous amyloid beta protein determines K+ current expression levels in rat cerebellar granule neurones, 2002

Plant LD, Boyle JP, Henderson Z, Kemp PJ, Peers C, Pearson HA Chronic hypoxia augments the standing outward K+ current in rat central neurones via an increase in endogenous amyloid beta protein levels, 2002

Smith IF, Boyle JP, Pearson HA, Peers C Chronic hypoxia inhibits Na+-Ca+ exchange and elevates mitochondrial [Ca2+] in rat type 1 cortical astrocytes, 2002

Smith IF, Boyle JP, Vaughan PFT, Pearson HA, Cowburn RF, Peers CS Ca2+ Stores and capacitative Ca2+ entry in human neuroblastoma (SH-SY5Y) cells expressing a familial Alzheimer's disease presenilin-1 mutation BRAIN RESEARCH 949 105-111, 2002
DOI:10.1016/S0006-8993(02)02970-0

Plant LD, Kemp PJ, Peers C, Henderson Z, Pearson HA Hypoxic Depolarization of Cerebellar Granule Neurons by Specific Inhibition of TASK-1 Stroke 33 2324-2328, 2002
DOI:10.1161/01.STR.0000027440.68031.B0
View abstract

Kemp P, Plant LD, Peers C, Henderson Z, Pearson HA Hypoxic depolarization of central neurones. by specific inhibition of TASK-1 FASEB J 16 A61-A61, 2002

Plant L, Boyle JP, Thomas NM, Hipkins NJ, Benedikz E, Hooper NM, Henderson Z, Vaughan PFT, Peers C, Cowburn RF, Pearson HA Presenilin-1 mutations alter K+ currents in the human neuroblastoma cell line, SH-SY5Y. NeuroReport 13 1553-1556, 2002
DOI:10.1097/00001756-200208270-00013

Smith IF, Boyle JP, Vaughan PFT, Pearson HA, Peers C Effects of chronic hypoxia on Ca<sup>2+</sup>stores and capacitative Ca<sup>2+</sup>entry in human neuroblastoma (SH-SY5Y) cells Journal of Neurochemistry 79 877-884, 2001
DOI:10.1046/j.1471-4159.2001.00620.x

Ramsden M, Plant LD, Webster NJ, Vaughan PFT, Henderson Z, Pearson HA Differential effects of unaggregated and aggregated amyloid beta protein (1-40) on K+ channel currents in primary cultures of rat cerebellar granule and cortical neurones J NEUROCHEM 79 699-712, 2001

Shukla C, Plant LD, Finch LH, Grumbridge S, Henderson Z, Bridges LR, Pearson HA Differential effects of antioxidants on A beta- and H2O2- induced cell death in the SHSY-5Y neuronal cell-line Journal of Cellular Pathology 5 241-250, 2001

Jiang LH, Gawler DJ, Hodson N, Milligan CJ, Pearson HA, Porter V, Wray D Regulation of cloned cardiac L-type calcium channels by cGMP-dependent protein kinase Journal of Biological Chemistry 275 6135-6143, 2000
View abstract

McManus A, Ramsden M, Murray M, Henderson Z, Pearson HA, Campbell VA Enhancement of 45Ca2+ influx and voltage dependent Ca2 channel activity by beta-amyloid (1-40) in rat cortical synaptosomes and cultured cortical neurons: modulation by the proinflammatory cytokine interleukin-1Beta Journal of Biological Chemistry 275 4713-4719, 2000

Price SA, Held B, Pearson HA Amyloid beta protein increases Ca2+ currents in rat cerebellar granule neurones NeuroReport 9 539-545, 1998

Held B, Pocock JM, Pearson HA Endothelin-1 inhibits voltage-sensitive Ca2+ channels in cultured rat cerebellar granule neurones via the endothelin-A receptor. Pflugers Archiv: European Journal of Physiology 436 766-775, 1998