Professor Jonathan D Cooper  BSc PhD
Professor of Experimental Neuropathology

email	contact this person
tel	020 7848 0286
fax	020 7848 0986
address	Department of Neuroscience, Centre for the Cellular Basis of Behaviour and MRC Centre for Neurodegeneration Research, The James Black Centre, The Institute of Psychiatry King's College London 125 Coldharbour Lane, London, SE5 9NU
location	2-056 James Black Centre
departments	MRC Centre for Neurodegeneration Research Neurodegeneration and Brain Injury Neuroscience
also	Batten Disease / Pediatric Storage Disorders laboratory (PSDL) Centre for the Cellular Basis of Behaviour (CCBB)

biography

Jon Cooper is a Professor in the Department of Neuroscience and leads the research efforts of the Pediatric Storage Disorders Laboratory (PSDL). His research continues to center upon understanding why particular neuronal populations are selectively vulnerable in a range of neurodegenerative conditions.

These studies have concentrated upon the basal forebrain cholinergic neurons (BFCNs) that degenerate in conditions such as Alzheimer’s disease and normal aging. The powerful influence of neurotrophins, such as nerve growth factor, upon the survival and phenotype of BFCNs has been a particular interest, most recently explored in models of Down syndrome.

Since moving to the Institute in 2000, research in the PSDL has focused upon the neurobiology of Batten Disease or neuronal ceroid lipofuscinosis (NCLs). Batten disease is the collective name for a group of neurodegenerative childhood disorders that invariably prove fatal, with no effective treatment available. Together with colleagues in the US, Europe and New Zealand, we are working to discover precisely how Batten disease affects the brain.

The main thrust of this work is to study patterns of neurodegeneration in mouse and large animal models of NCL, comparing our findings with the brains of affected individuals. In this manner we can identify and follow the earliest effects of disease and discover how and why these changes subsequently develop. These studies not only provide us with important landmarks of disease progression, but also the ability to judge the efficacy of candidate therapeutic strategies.

Particular interests include; the comparative study of NCL pathogenesis; the role of neuroimmune and autoimmune responses in the NCLs and other storage disorders; the developmental neurobiology of the NCLs; assessment of therapeutic efficacy.

activities and interests

Head of Pediatric Storage Disorders Laboratory
Neurobiology of Batten disease or Neuronal Ceroid Lipofuscinosis
Neurodegenerative Mechanisms
Comparative Neuropathology
Quantitative Morphology
Stereology

teaching activities

skills

Quantitative morphology of murine, large animal and human CNS
Stereology
Immunohistochemistry
Confocal microscopy

publications

Macauley SL, Roberts MS, Wong AM, McSloy F, Reddy AS, Cooper JD, Sands MS (2012). Synergistic effects of central nervous system-directed gene therapy and bone marrow transplantation in the murine model of infantile neuronal ceroid lipofuscinosis. Ann Neurol. 2012 Feb 1. doi: 10.1002/ana.23545. [Epub ahead of print]

Roberts MS, Macauley SL, Wong AM, Yilmas D, Hohm S, Cooper JD, Sands MS (2012). Combination small molecule PPT1 mimetic and CNS-directed gene therapy as a treatment for infantile neuronal ceroid lipofuscinosis. J Inherit Metab Dis. 2012 Feb 7. [Epub ahead of print]

Nunes A, Pressey SN, Cooper JD, Soriano S (2011). Loss of amyloid precursor protein in a mouse model of Niemann-Pick type C disease exacerbates its phenotype and disrupts tau homeostasis. Neurobiol Dis. 2011 Feb 16. [Epub ahead of print]

Farfel-Becker T, Vitner EB, Pressey SN, Eilam R, Cooper JD, Futerman AH (2011). Spatial and temporal correlation between neuron loss and neuroinflammation in a mouse model of neuronopathic Gaucher disease. Hum Mol Genet. 2011 Jan 27. [Epub ahead of print]

Kovács AD, Saje A, Wong A, Szénási G, Kiricsi P, Szabó E, Cooper JD, Pearce DA (2011). Temporary inhibition of AMPA receptors induces a prolonged improvement of motor performance in a mouse model of juvenile Batten disease. Neuropharmacology. 60, 405-409.

Seehafer SS, Ramirez-Montealegre D, Wong AM, Chan CH, Castaneda J, Horak M, Ahmadi SM, Lim MJ, Cooper JD, Pearce DA (2011). Immunosuppression alters disease severity in juvenile Batten disease mice. J Neuroimmunol. 230, 169-172. 2010 Oct 9

Cooper JD (2010). The neuronal ceroid lipofuscinoses: the same, but different? Biochem Soc Trans. 38, 1448-1452.

Wong AM, Rahim AA, Waddington SN, Cooper JD (2010). Current therapies for the soluble lysosomal forms of neuronal ceroid lipofuscinosis. Biochem Soc Trans. 38, 1484-1488.

Rahim AA, Wong AM, Buckley SM, Chan JK, David AL, Cooper JD, Coutelle C, Peebles DM, Waddington SN (2010). In utero gene transfer to the mouse nervous system. Biochem Soc Trans. 38, 1489-1493.

Pressey SNR, O’Donnell KJ, Stauber T, Fuhrmann JC, Tyynelä J, Jentsch TJ, Cooper JD (2010) Distinct neuropathological phenotypes after disrupting the chloride transport proteins ClC-6 or ClC-7/Ostm1. J. Neuropathol. Exp. Neurol. 69, 1228-1246.

Buonocore F, Hill MJ, Campbell CD, Oladimeji PB, Jeffries AR, Troakes C, Hortobagyi T, Williams BP, Cooper JD, Bray NJ (2010). Effects of cis-regulatory variation differ across regions of the adult human brain. Hum Mol Genet. 19, 4490-4496.

Li Y, Hu J, Höfer K, Wong AMS, Cooper JD, Birnbaum SG, Hammer RE, Hofmann SL (2010). DHHC5 Interacts With PDZ Domain 3 Of Post-Synaptic Density-95 (PSD-95) Protein And Plays A Role In Learning And Memory. J Biol Chem 285, 13022-13031.

Tamaki SJ, Jacobs Y, Dohse M, Capela A, Cooper JD, Reitsma M, He D, Tushinski R, Belichenko PV, Salehi A, Mobley WC, Gage FH, Huhn S, Tsukamoto AS, Weissman IL, Uchida N (2009) Neuroprotection of Host Cells by Human Central Nervous System-Stem Cells in a Mouse Model of Infantile Neuronal Ceroid Lipofuscinosis Cell Stem Cell 5, 310–319

Kielar C, Wishart TM, Palmer A, Dihanich S, Wong AM, Macauley SL, Chan CH, Sands MS, Pearce DA, Cooper JD, Gillingwater TH (2009). Molecular correlates of axonal and synaptic pathology in mouse models of Batten disease. Hum Mol Genet. 18, 4066-80

von Schantz C, Kielar C, Hansen SN, Pontikis CC, Alexander NA, Kopra O, Jalanko A, Cooper JD (2009). Progressive thalamocortical neuron loss in Cln5 deficient mice: distinct effects in Finnish variant late infantile NCL. Neurobiol. Dis. 34, 308-319.

Weimer JM, Benedict JW, Getty AL, Pontikis CC, Lim MJ, Cooper JD, Pearce DA (2009). Cerebellar defects in a mouse model of juvenile neuronal ceroid lipofuscinosis. Brain Res. 1266, 93-107.

Macauley SL, Wozniak DF, Kielar C, Tan Y, Cooper JD, Sands MS (2009). Cerebellar Pathology and Motor Deficits in the Palmitoyl Protein Thioesterase 1- Deficient Mouse. Exp Neurol. 217, 124-135.

Rahim AA, Wong AM, Howe SJ, Buckley SM, Acosta-Saltos AD, Elston KE, Ward NJ, Philpott NJ, Cooper JD, Anderson PN, Waddington SN, Thrasher AJ, Raivich G (2009). Efficient gene delivery to the adult and fetal CNS using pseudotyped non-integrating lentiviral vectors. Gene Ther. 16, 509-520.

Oswald MJ, Palmer DN, Kay GW, Barwell KJ, Cooper JD (2008). Location and connectivity determine GABAergic interneuron survival in the brains of South Hampshire sheep with CLN6 neuronal ceroid lipofuscinosis. Neurobiol Dis. 32, 50-65.

Cooper JD (2008). Moving towards therapies for Juvenile Batten disease? Exp Neurol. 211, 329-331.

von Schantz C, Kopra O, Cooper JD , Gentile M, Hovatta I, Saharinen J, Peltonen L, Jalanko A (2008). Brain gene expression profiles of Cln1 and Cln5 deficient mice unravels common molecular pathways underlying neuronal degeneration in NCL diseases. BMC Genomics, 9: 146

Partanen S, Haapanen A, Kielar C, Pontikis C, Alexander N, Inkinen T, Saftig P, Gillingwater TH, Cooper JD, Tyynelä J. Synaptic changes in the thalamocortical system of cathepsin D deficient mice, a model of human congenital neuronal ceroid-lipofuscinosis. J Neuropathol Exp Neurol. 67, 16-29.

Chang M, Cooper JD, Sleat DE, Cheng SH, Dodge JC, Passini MA, Lobel P, Davidson BL (2008). Intraventricular enzyme replacement improves disease phenotypes in a mouse model of late infantile neuronal ceroid lipofuscinosis. Mol Ther. 16, 649-56.

Castaneda JA, Lim MJ, Cooper JD, Pearce DA (2008). Immune system irregularities in lysosomal storage disorders. Acta Neuropathol. 115, 159-74.

Weimer JM, Elshatory YM, Short DW, Ramirez-Montealegre D, Benedict JW, Ryan DA, Alexander NA, Federoff HJ, Cooper JD, Pearce DA (2007). Alterations in striatal dopamine catabolism precede loss of substantia nigra neurons in a mouse model of Juvenile Neuronal Ceroid Lipofuscinosis. Brain Res. 1162, 98-112.

Pears MR, Rubtsov D, Mitchison HM, Cooper JD, Pearce DA, Mortishire-Smith RJ, Griffin JL (2007). Strategies for data analyses in a high resolution H-1 NMR based metabolomics study of a mouse model of Batten disease. Metabolomics 3, 121-136

Lim MJ, Alexander N, Benedict JW, Chattopadhyay S, Shemilt SJA, Guérin CJ, Cooper JD, Pearce DA (2007). IgG entry and deposition are components of the neuroimmune response in Batten Disease. Neurobiol. Dis. 25, 239-51.

Kielar C, Maddox L, Bible E, Pontikis CC, Macauley SL, Griffey MA, Wong M, Sands MS, Cooper JD (2007). Successive neuron loss in the thalamus and cortex in a mouse model of infantile neuronal ceroid lipofuscinosis. Neurobiol. Dis. 25, 150-62.

Cooper JD (2006). Laser microdissection for research into the molecular neuropathology of Batten Disease. Microscopy and Analysis 20, 11-12.

Cooper JD, Russell CR, Mitchison HM (2006). Progress towards understanding disease mechanisms in small vertebrate models of neuronal ceroid lipofuscinosis. Biochim Biophys Acta 1762, 873-889

Kay GW , Palmer DN, Rezaie P, Cooper JD (2006). Prenatal activation of non-neuronal cells within the developing CNS of sheep with neuronal ceroid lipofuscinosis (CLN6). Brain Pathol. 16, 110-116.

Lim MJ, Beake J, Bible E, Curran TM, Ramirez-Montealegre D, Pearce DA, Cooper JD (2006). Distinct patterns of serum immunoreactivity as evidence for multiple brain directed autoantibodies in Juvenile Neuronal Ceroid Lipofuscinosis. Neuropathology and Applied Neurobiology 32, 469-482.

Weimer JM, Custer AW, Benedict JW, Alexander NA, Kingsley E, Federoff HJ, Cooper JD, Pearce DA (2006). Visual deficits in a mouse model of Batten disease are the result of optic nerve degeneration and loss of dorsal lateral geniculate thalamic neurons. Neurobiol. Dis. 22, 284-293.

Griffey MA, Wozniak D, Wong M, Bible E, Johnson K, Rothman MR, Wentz AE, Cooper JD, Sands MS (2006). CNS-directed AAV2-mediated gene therapy ameliorates functional deficits in a murine model of infantile neuronal ceroid lipofuscinosis. Molecular Therapy 15, 538-547.

Pears MR, Cooper JD, Mitchison HM, Mortishire-Smith RJ, Pearce DA, Griffin JL (2005). High resolution 1 H NMR based metabolomics indicates a neurotransmitter cycling deficit in cerebral tissue from a mouse model of Batten disease. Journal of Biological Chemistry 280, 42508-42514.

Pontikis CC, Cotman SL, MacDonald ME, Cooper JD (2005). Thalamocortical neuron loss and localized astrocytosis in the Cln3 D ex7/8 knock-in mouse model of Batten disease. Neurobiol. Dis 20, 823-836.

Oswald MJ, Palmer DN , Kay GW, Shemilt SJA,Rezaie P ,Cooper JD (2005). Glial activation spreads from specific cerebral foci and precedes neurodegeneration in presymptomatic ovine neuronal ceroid lipofuscinosis (CLN6). Neurobiol. Dis. 20, 49-63.

Tyynelä J, Cooper JD, Khan MN, Shemilt SJA, Haltia M (2004). Specific Patterns of Storage Deposition, Neurodegeneration, and Glial Activation in the Hippocampus of Patients with Neuronal Ceroid-Lipofuscinoses.Brain Pathol.14, 349-357.

Pontikis CC, Cella CV, Parihar N, Lim MJ, ChakrabartiS, Mitchison HM, Mobley WC, Rezaie P, Pearce DA, Cooper JD (2004). L ate onset neurodegeneration in the Cln3-/- mouse model of juvenile neuronal ceroid lipofuscinosis is preceded by low level glial activation . Brain Research 1023, 231-242

Bible E, GuptaP, Hofmann SL, Cooper JD (2004) Regional and cellular neuropathology in the palmitoyl protein thioesterase-1 (PPT1) null mutant mouse model of infantile neuronal ceroid lipofuscinosis. Neurobiol. Dis.16, 346-359.

Griffey M, Bible C, Vogler C, Levy B, Gupta P, Cooper JD, Sands MS (2004). Adeno-associated virus 2 -mediated gene therapy decreases autofluorescent storage material and increases brain mass in a murine model of Infantile Neuronal Ceroid Lipofuscinosis (INCL). Neurobiol. Dis. 16, 360-369.

Mitchison HM, Lim MJ, Cooper JD (2004). Selectivity and Types of Cell Death in the Neuronal Ceroid Lipofuscinoses (NCLs). Brain Pathol.14, 86-96.

Heine C, Tyynela J, Cooper JD, Palmer DN, Elleder M, Kohlschutter A, Braulke T. (2003). Enhanced expression of manganese-dependent superoxide dismutase in human and ovine CLN6 tissues. Biochem J. 376, 369-376.

Cooper JD. (2003). Progress towards understanding the neurobiology of Batten disease or neuronal ceroid lipofuscinosis.Curr. Opin. Neurol. 16, 121-128

Chattopadhyay S, Ito M, Cooper JD, Brooks AI, Curran TM, Powers JM, Pearce DA. (2002).An Autoantibody Inhibitory to Glutamic Acid Decarboxylase in the Neurodegenerative Disorder Batten Disease. Hum. Mol. Genet. 11, 1421-1431.

Mitchison HM, Bernard DJ, Greene NDE, Cooper JD, Junaid MA, Pullarkat RK, Vos N, Breuning MH, Owens JW, Mobley WC, Gardiner RM, Lake BD, Taschner PEM, Nussbaum RL. (1999). Targeted Disruption of the Cln3 gene provides a mouse model for Batten Disease. The Batten Mouse Model Consortium. Neurobiol. Dis. 6, 321-334.

Cooper JD, Messer A, Feng AK, Chua-Couzens J, Mobley WC. (1999). Apparent loss and hypertrophy of interneurons in a mouse model of neuronal ceroid lipofuscinosis: evidence for partial response to insulin-like growth factor-1 treatment. J. Neurosci. 19, 2556-2567.

last updated: Thursday, March 15, 2012