Dr Stephanie Schorge

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Personal Profile

Name: Stephanie Schorge Email: s.schorge@ucl.ac.uk
Title: Dr Tel: 020 3448 4208
Department: Clinical & Experimental Epilepsy Fax:
Position: Principal Research Associate Address: Queen Square, UCL Institute of Neurology, London, WC1N 3BG
Research Domain: Basic Life Sciences, Neuroscience, Personalised Medicine Web Page: Personal Web Page

Profile

Research Description

We are interested in how ion channels alter neurological disorders (such as epilepsy and ataxias) and also how neurological disorders alter ion channels. In particular we are interested in how alternative splicing in ion channels changes their behaviour, and how changes caused by splicing may lead to changes in the course and treatment of diseases. Voltage-gated ion channels are often subject to extensive alternative splicing and the functional and neurological impact of changes in this splicing, as well as the factors regulating it are currently largely unknown. In the lab we regularly record from sodium, potassium, calcium and chloride channels. A close collaboration with the Experimental epilepsy group at IoN involved developing viral-mediated expression to permit heterologous expression of ion channels in difficult to transfect cells, and a close collaboration with the MRC-funded Neuromuscular Centre at IoN means we have a regular stream of novel mutations identified in patients to investigate as well as normally occurring splice variants. We have experimented with a variety of model systems, from oocytes to differentiated teratoma cells, and are constantly looking for ways to better reproduce the cellular environments that are relevant for the changes in ion channel behaviour. S.Schorge is funded by a fellowship endowed by the Worshipful Company of Pewterers.

Research Activities

Cellular mechanisms underlying neurodegeneration

Experimental epilepsy

Function of single synapses

Molecular mechanisms of cell surface receptor function

Regulation, alternative splicing and modulation of ion channels changes in development and neurological disorders

Education Description

UCL Collaborators

Prof Parmjit Jat; Prof Josef Kittler; Prof John Hardy; Dr Kirill Volynski; Prof Ivan Gout; Prof John Collinge; Prof Dmitri Rusakov; Dr Andrea Townsend-Nicholson; Prof Sarah Tabrizi; Dr Peter-Christian Kloehn; Prof Dimitri Michael Kullmann; Dr Leslie Dale; Prof Matthew Walker; Prof Mike O'hare

External Collaborators

Publications

    2014

    • Kullmann DM, Schorge S, Walker MC, Wykes RC (2014). Gene therapy in epilepsy-is it time for clinical trials?. Nat Rev Neurol, , - . doi:10.1038/nrneurol.2014.43
    • Kätzel D, Nicholson E, Schorge S, Walker MC, Kullmann DM (2014). Chemical-genetic attenuation of focal neocortical seizures.. Nat Commun, 5, 3847 - . doi:10.1038/ncomms4847
    • Bettencourt C, Ryten M, Forabosco P, Schorge S, Hersheson J, Hardy J, Houlden H, for the United Kingdom Brain Expression Consortium (2014). Insights From Cerebellar Transcriptomic Analysis Into the Pathogenesis of Ataxia.. JAMA Neurol, , - . doi:10.1001/jamaneurol.2014.756
    • Schorge S, Ishikawa K (2014). Ataxia and CACNA1A: Episodic or Progressive. In Weiss N, Koschak A (Ed.), Pathologies of Calcium Channels (pp. 27 - 45). : Springer-Verlag.
    • Menzler K, Hermsen A, Balkenhol K, Duddek C, Bugiel H, Bauer S, Schorge S, Reif PS, Klein KM, Haag A, Oertel WH, Hamer HM, Knake S, Trucks H, Sander T, Rosenow F, for the EPICURE-Consortium (2014). A common SCN1A splice-site polymorphism modifies the effect of carbamazepine on cortical excitability-A pharmacogenetic transcranial magnetic stimulation study.. Epilepsia, , - . doi:10.1111/epi.12515

    2013

    • Walker MC, Schorge S, Kullmann DM, Wykes RC, Heeroma JH, Mantoan L (2013). Gene therapy in status epilepticus.. Epilepsia, 54 Suppl 6, 43 - 45. doi:10.1111/epi.12275
    • Kullmann D, Heeroma J, Mantoan L, Wykes R, Kaetzel D, Chabrol E, Schorge S, Walker M (2013). Gene therapy in experimental focal neocortical epilepsy.
    • Burge JA, Hanna MG, Schorge S (2013). Nongenomic actions of progesterone and 17β-estradiol on the chloride conductance of skeletal muscle.. Muscle Nerve, 48(4), 589 - 591. doi:10.1002/mus.23887
    • Tomlinson SE, Rajakulendran S, Tan SV, Graves TD, Bamiou DE, Labrum RW, Burke D, Sue CM, Giunti P, Schorge S, Kullmann DM, Hanna MG (2013). Clinical, genetic, neurophysiological and functional study of new mutations in episodic ataxia type 1.. J Neurol Neurosurg Psychiatry, 84(10), 1107 - 1112. doi:10.1136/jnnp-2012-304131
    • Wanisch K, Kovac S, Schorge S (2013). Tackling obstacles for gene therapy targeting neurons: disrupting perineural nets with hyaluronidase improves transduction.. PLoS One, 8(1), e53269 - . doi:10.1371/journal.pone.0053269

    2012

    • Wykes RC, Heeroma JH, Mantoan L, Zheng K, MacDonald DC, Deisseroth K, Hashemi KS, Walker MC, Schorge S, Kullmann DM (2012). Optogenetic and potassium channel gene therapy in a rodent model of focal neocortical epilepsy.. Sci Transl Med, 4(161), 161ra152 - . doi:10.1126/scitranslmed.3004190
    • Raheem O, Penttilä S, Suominen T, Kaakinen M, Burge J, Haworth A, Sud R, Schorge S, Haapasalo H, Sandell S, Metsikkö K, Hanna M, Udd B (2012). New immunohistochemical method for improved myotonia and chloride channel mutation diagnostics.. Neurology, 79(22), 2194 - 2200. doi:10.1212/WNL.0b013e31827595e2
    • Raheem O, Penttila S, Suominen T, Kaakinen M, Burge J, Haworth A, Sud R, Schorge S, Haapasalo H, Sandell S, Metsikko K, Hanna M, Udd B (2012). New immunohistochemical method for improved myotonia and chloride channel mutation diagnostics. doi:10.1016/j.nmd.2012.06.314
    • Raja Rayan DL, Haworth A, Sud R, Matthews E, Fialho D, Burge J, Portaro S, Schorge S, Tuin K, Lunt P, McEntagart M, Toscano A, Davis MB, Hanna MG (2012). A new explanation for recessive myotonia congenita: exon deletions and duplications in CLCN1.. Neurology, 78(24), 1953 - 1958. doi:10.1212/WNL.0b013e318259e19c
    • Farmer C, Cox JJ, Fletcher EV, Woods CG, Wood JN, Schorge S (2012). Splice variants of Na(V)1.7 sodium channels have distinct β subunit-dependent biophysical properties.. PLoS One, 7(7), e41750 - . doi:10.1371/journal.pone.0041750
    • Burge J, Schorge S, Hanna MG (2012). Progesterone reduces and shifts the voltage dependence of the skeletal muscle chloride conductance.

    2011

    • Mantoan L, Wykes R, Schorge S, Walker MC, Kullmann DM (2011). OPTOGENETIC INHIBITION OF EPILEPTIC ACTIVITY.
    • Fletcher EV, Kullmann DM, Schorge S (2011). Alternative splicing modulates inactivation of type 1 voltage-gated sodium channels by toggling an amino acid in the first S3-S4 linker.. J Biol Chem, 286(42), 36700 - 36708. doi:10.1074/jbc.M111.250225
    • Wykes RC, Heeroma JH, Kullmann DM, Walker MC, Schorge S (2011). LENTIVIRAL-MEDIATED OVEREXPRESSION OF THE POTASSIUM CHANNEL KV1.1 AS A TREATMENT FOR FOCAL NEOCORTICAL EPILEPSY.

    2010

    • Rajakulendran S, Schorge S, Kullmann DM, Hanna MG (2010). Dysfunction of the Ca(V)2.1 calcium channel in cerebellar ataxias.. F1000 Biol Rep, 2, - . doi:10.3410/B2-4
    • Eddaoudi A, Townsend-Nicholson A, Timms JF, Schorge S, Jayasinghe SN (2010). Molecular characterisation of post-bio-electrosprayed human brain astrocytoma cells. Analyst, 135(10), 2600 - 2612. doi:10.1039/C0AN00213E
    • Schorge S, van de Leemput J, Singleton A, Houlden H, Hardy J (2010). Human ataxias: a genetic dissection of inositol triphosphate receptor (ITPR1)-dependent signaling.. Trends Neurosci, 33(5), 211 - 219. doi:10.1016/j.tins.2010.02.005
    • Schorge S, Matthews E, Kullmann DM, Hanna MG (2010). VOLTAGE SENSOR CHARGE LOSS ACCOUNTS FOR MOST CASES OF HYPOKALEMIC PERIODIC PARALYSIS Reply. NEUROLOGY, 74(3), 269 - 270.
    • Rajakulendran S, Graves TD, Labrum RW, Kotzadimitriou D, Eunson L, Davis MB, Davies R, Wood NW, Kullmann DM, Hanna MG, Schorge S (2010). Genetic and functional characterisation of the P/Q calcium channel in episodic ataxia with epilepsy.. J Physiol, 588(Pt 11), 1905 - 1913. doi:10.1113/jphysiol.2009.186437
    • Schorge S, Kullmann DM (2010). Sodium channel mutations and epilepsy: association and causation.. Exp Neurol, 226(1), 8 - 10. doi:10.1016/j.expneurol.2010.08.008
    • Schorge S, Kullmann DM (2010). Sodium channel mutations and epilepsy: Association and causation. EXP NEUROL, 226(1), 8 - 10. doi:10.1016/j.expneuro1.2010.08.008
    • Rajakulendran S, Labrum RW, Graves TD, Tomlinson S, Eunson LH, Davis MB, Schorge S, Kullmann DM, Hanna MG (2010). PAW31 Clinical and genetic spectrum of the episodic ataxias: the UK perspective.. J Neurol Neurosurg Psychiatry, 81(11), e32 - . doi:10.1136/jnnp.2010.226340.59
    • Graves TD, Rajakulendran S, Zuberi SM, Morris HR, Schorge S, Hanna MG, Kullmann DM (2010). Nongenetic factors influence severity of episodic ataxia type 1 in monozygotic twins.. Neurology, 75(4), 367 - 372. doi:10.1212/WNL.0b013e3181ea9ee3

    2009

    • Heeroma JH, Henneberger C, Rajakulendran S, Hanna MG, Schorge S, Kullmann DM (2009). Episodic ataxia type 1 mutations differentially affect neuronal excitability and transmitter release.. Dis Model Mech, 2(11-12), 612 - 619. doi:10.1242/dmm.003582
    • Rajakulendran S, Graves T, Kullmann D, Schorge S, Hanna M (2009). Variation in CACNA1A associated with episodic ataxia and epilepsy.
    • Schorge S, Walker MC (2009). A self-activating intrinsic brake on bursting in CA3 neurons. The Journal of Physiology, 587(6), 1143 - 1144. doi:10.1113/jphysiol.2009.170027
    • Matthews E, Labrum R, Sweeney MG, Sud R, Haworth A, Chinnery PF, Meola G, Schorge S, Kullmann DM, Davis MB, Hanna MG (2009). Voltage sensor charge loss accounts for most cases of hypokalemic periodic paralysis. Neurology, 72(18), 1544 - 1547. doi:10.1212/01.wnl.0000342387.65477.46
    • Schorge S, Kullmann DM (2009). Sodium channelopathy of peripheral nerve: tightening the genotype-phenotype relationship. Brain, 132(7), 1690 - 1692. doi:10.1093/brain/awp120
    • Rajakulendran S, Tan SV, Matthews E, Tomlinson SE, Labrum R, Sud R, Kullmann DM, Schorge S, Hanna MG (2009). A patient with episodic ataxia and paramyotonia congenita due to mutations in KCNA1 and SCN4A.. Neurology, 73(12), 993 - 995. doi:10.1212/WNL.0b013e3181b87959
    • Labrum RW, Rajakulendran S, Graves TD, Eunson LH, Bevan R, Sweeney MG, Hammans SR, Tubridy N, Britton T, Carr LJ, Ostergaard JR, Kennedy CR, Al-Memar A, Kullmann DM, Schorge S, Temple K, Davis MB, Hanna MG (2009). Large scale calcium channel gene rearrangements in episodic ataxia and hemiplegic migraine: implications for diagnostic testing.. J Med Genet, 46(11), 786 - 791. doi:10.1136/jmg.2009.067967

    2008

    • Graves T, Morris H, Zuberi S, Kullmann D, Schorge S, Hanna M (2008). Episodic ataxia type 1 in identical twins: Genotype-phenotype correlation.
    • Graves TD, Morris H, Zuberi S, Hanna MG, Kullmann DM, Schorge S (2008). Episodic ataxia type 1 in twins: Genotype-phenotype correlation.
    • Graves TD, Zuberi SM, Morris H, Schorge S, Kullmann DM, Hanna MG (2008). Episodic ataxia type 1 in identical twins: genotype-phenotype correlation.
    • Fialho D, Kullmann DM, Hanna MG, Schorge S (2008). Non-genomic effects of sex hormones on CIC-1 may contribute to gender differences in myotonia congenita. doi:10.1016/j.nmd.2008.06.076
    • Kullmann DM, Schorge S (2008). Voltage-gated ion channels: molecular biology and role of mutations in epilepsy. In Engel J, Pedley TA (Ed.), Epilepsy: a comprehensive textbook (pp. 253 - 265). : Wolters Kluwer, Lippincott Williams & Wilkins.
    • Graves TD, Zuberi SM, Morris H, Schorge S, Kullmann DM, Hanna MG (2008). Episodic ataxia type 1 in identical twins. doi:10.1016/j.nmd.2008.06.079
    • Fialho D, Kullmann DM, Hanna MG, Schorge S (2008). Non-genomic effects of sex hormones on CLC-1 may contribute to gender differences in myotonia congenita. Neuromuscular Disorders, 18(11), 869 - 872. doi:10.1016/j.nmd.2008.07.004

    2007

    • Graves TD, Zuberi SM, Schorge S, Kullmann DM, Hanna MG (2007). A clinical, genetic and electrophysiological study of a new UK episodic ataxia type 1 (EA1) pedigree.
    • Rajakulendran S, Schorge S, Kullmann DM, Hanna MG (2007). Episodic ataxia type 1: a neuronal potassium channelopathy. Neurotherapeutics, 4(2), 258 - 266. doi:10.1016/j.nurt.2007.01.010
    • Graves TD, Schorge S, Morris H, Kullmann DM, Hanna MG (2007). A novel voltage-sensing mutation in Kv1.1 is associated with episodic ataxia type 1.
    • Graves TD, Zuberi SM, Schorge S, Kullmann DM, Hanna MG (2007). A clinical, genetic and electrophysiological study of a new UK episodic ataxia type 1 pedigree.
    • Fialho D, Schorge S, Pucovska U, Davies NP, Labrum R, Haworth A, Stanley E, Sud R, Wakeling W, Davis MB, Kullmann DM, Hanna MG (2007). Chloride channel myotonia: exon 8 hot-spot for dominant-negative interactions.. Brain, 130(12), 3265 - 3274. doi:10.1093/brain/awm248

    2006

    • Scimemi A, Schorge S, Kullmann DM, Walker MC (2006). Epileptogenesis is associated with enhanced glutamatergic transmission in the perforant path. Journal of Neurophysiology, 95(2), 1213 - 1220.
    • Graves TD, Schorge S, Davies RA, Wood NW, Kullmann DM, Hanna MG (2006). The role of the brain P/Q-type calcium channel in human epilepsy. EUR J NEUROL, 13, 313 - 313.
    • Schorge S, Ptácek LJ (2006). Inherited erythermalgia moves a sodium channel into focus.. Neurology, 67(9), 1538 - 1539. doi:10.1212/01.wnl.0000242618.60344.8c

    2005

    • Tate SK, Depondt C, Sisodiya SM, Cavalleri GL, Schorge S, Soranzo N, Thom M, Sen A, Shorvon SD, Sander JW, Wood NW, Goldstein DB (2005). Genetic predictors of the maximum doses patients receive during clinical use of the anti-epileptic drugs carbamazepine and phenytoin.. Proceedings of the National Academy of Sciences of the United States of America, 102(15), 5507 - 5512. doi:10.1073/pnas.0407346102
    • King BF, Liu M, Townsend-Nicholson A, Pfister J, Padilla F, Ford AP, Gever JR, Oglesby IB, Schorge S, Burnstock G (2005). Antagonism of ATP responses at P2X receptor subtypes by the pH indicator dye, Phenol red.. British Journal of Pharmacology, 145(3), 313 - 322. doi:10.1038/sj.bjp.0706187
    • Schorge S, Elenes S, Colquhoun D (2005). Maximum likelihood fitting of single channel NMDA activity with a mechanism composed of independent dimers of subunits. The Journal of Physiology, 569(2), 395 - 418. doi:10.1113/jphysiol.2005.095349
    • Schorge S, Scimemi A, Kullmann DM (2005). Regulation of sodium channel alternative splicing in rat cortex.

    2003

    • Schorge S, Colquhoun D (2003). Studies of NMDA receptor function and stoichiometry with truncated and tandem subunits. Journal of Neuroscience, 23(4), 1151 - 1158.

    1999

    • Lin Z, Lin Y, Schorge S, Pan JQ, Beierlein M, Lipscombe D (1999). Alternative splicing of a short cassette exon in alpha1B generates functionally distinct N-type calcium channels in central and peripheral neurons.. J Neurosci, 19(13), 5322 - 5331.

    1997

    • Lin Z, Haus S, Edgerton J, Lipscombe D (1997). Identification of functionally distinct isoforms of the N-type Ca2+ channel in rat sympathetic ganglia and brain.. Neuron, 18(1), 153 - 166.