Jeffrey L. Noebels, M.D., Ph.D.

Professor of Neurology, Neuroscience, and
Molecular and Human Genetics

Director, Blue Bird Circle Developmental Neurogenetics Laboratory

Medical School

M.D. (1981) Yale University

Graduate School

Ph.D. (1977) Stanford University

Clinical Interests

Epilepsy and Inherited Neurological Disease

Research Interests

Large scale discovery of genetic sequence errors in human ion channel genes in patients with epilepsy. Experimental mutational analysis to learn how genes regulate excitability in the developing central nervous system. Molecular studies of activity-induced changes in neural gene expression, signaling between neurons and glia, and seizure-induced excitotoxicity. Analysis of mutant mouse models of inherited neurological disorders using molecular anatomy, patch clamp physiology, imaging, EEG, and gene transfer into neurons.

Publications

Seal RP, Akil O, Yi E, Weber CM, Grant L, Yoo J, Clause A, Kandler K, Noebels JL, Glowatzki E, Lustig LR, Edwards RH. Sensorineural deafness and seizures in mice lacking vesicular glutamate transporter 3. Neuron 2008;57:263-75.
Bi W, Yan J, Shi X, Yuva-Paylor LA, Antalffy BA, Goldman A, Yoo JW, Noebels JL, Armstrong DL, Paylor R, Lupski JR. Rai1 deficiency in mice causes learning impairment and motor dysfunction, whereas Rai1 heterozygous mice display minimal behavioral phenotypes. Hum Mol Genet 2007;16:1802-13.
Glasscock E, Qian J, Yoo JW, Noebels JL. Masking epilepsy by combining two epilepsy genes. Nat Neurosci 2007;10:1554-8.
Lopez-Santiago LF, Meadows LS, Ernst SJ, Chen C, Malhotra JD, McEwen DP, Speelman A, Noebels JL, Maier SK, Lopatin AN, Isom LL. Sodium channel Scn1b null mice exhibit prolonged QT and RR intervals. J Mol Cell Cardiol 2007;43:636-47.
Noebels JL, Sidman RL. Persistent hypersynchronization of neocortical neurons in the mocha mutant of mouse. J Neurogenet 2007;21:253-6.
Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, Yoo J, Ho KO, Yu GQ, Kreitzer A, Finkbeiner S, Noebels JL, Mucke L. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron 2007;55:697-711.
Goldman A, Noebels J. Invited comments on the Shostak and Ottman review. Epilepsia 2006;47:1750-1; author reply 1755-6.
Goldman AM, Potocki L, Walz K, Lynch JK, Glaze DG, Lupski JR, Noebels JL. Epilepsy and chromosomal rearrangements in Smith-Magenis Syndrome [del(17)(p11.2p11.2)]. J Child Neurol 2006;21:93-8.
Noebels JL. The Judith Hoyer Lecture: genes, pixels, patterns, and prevention. Epilepsy Behav 2006;9:379-85.
Qian J, Noebels JL. Exocytosis of vesicular zinc reveals persistent depression of neurotransmitter release during metabotropic glutamate receptor long-term depression at the hippocampal CA3-CA1 synapse. J Neurosci 2006;26:6089-95.
Wang D, Pascual JM, Yang H, Engelstad K, Mao X, Cheng J, Yoo J, Noebels JL, De Vivo DC. A mouse model for Glut-1 haploinsufficiency. Hum Mol Genet 2006;15:1169-79.
Brenner R, Chen QH, Vilaythong A, Toney GM, Noebels JL, Aldrich RW. BK channel beta4 subunit reduces dentate gyrus excitability and protects against temporal lobe seizures. Nat Neurosci 2005;8:1752-9.
Cobos I, Calcagnotto ME, Vilaythong AJ, Thwin MT, Noebels JL, Baraban SC, Rubenstein JL. Mice lacking Dlx1 show subtype-specific loss of interneurons, reduced inhibition and epilepsy. Nat Neurosci 2005;8:1059-68.
Jankovic J, Noebels JL. Genetic mouse models of essential tremor: are they essential?. J Clin Invest 2005;115:584-6.
Noebels JL. Calcium channel ""gaiting"" and absence epilepsy. Epilepsy Curr 2005;5:95-7.
Qian J, Noebels JL. Visualization of transmitter release with zinc fluorescence detection at the mouse hippocampal mossy fibre synapse. J Physiol 2005;566:747-58.
Senechal KR, Thaller C, Noebels JL. ADPEAF mutations reduce levels of secreted LGI1, a putative tumor suppressor protein linked to epilepsy. Hum Mol Genet 2005;14:1613-20.
Chen C, Westenbroek RE, Xu X, Edwards CA, Sorenson DR, Chen Y, McEwen DP, O'Malley HA, Bharucha V, Meadows LS, Knudsen GA, Vilaythong A, Noebels JL, Saunders TL, Scheuer T, Shrager P, Catterall WA, Isom LL. Mice lacking sodium channel beta1 subunits display defects in neuronal excitability, sodium channel expression, and nodal architecture. J Neurosci 2004;24:4030-42.
Collins AL, Levenson JM, Vilaythong AP, Richman R, Armstrong DL, Noebels JL, David Sweatt J, Zoghbi HY. Mild overexpression of MeCP2 causes a progressive neurological disorder in mice. Hum Mol Genet 2004;13:2679-89.
May P, Rohlmann A, Bock HH, Zurhove K, Marth JD, Schomburg ED, Noebels JL, Beffert U, Sweatt JD, Weeber EJ, Herz J. Neuronal LRP1 functionally associates with postsynaptic proteins and is required for normal motor function in mice. Mol Cell Biol 2004;24:8872-83.
Mori M, Burgess DL, Gefrides LA, Foreman PJ, Opferman JT, Korsmeyer SJ, Cavalheiro EA, Naffah-Mazzacoratti MG, Noebels JL. Expression of apoptosis inhibitor protein Mcl1 linked to neuroprotection in CNS neurons. Cell Death Differ 2004;11:1223-33.
Zhang Y, Vilaythong AP, Yoshor D, Noebels JL. Elevated thalamic low-voltage-activated currents precede the onset of absence epilepsy in the SNAP25-deficient mouse mutant coloboma. J Neurosci 2004;24:5239-48.
Houseweart MK, Pennacchio LA, Vilaythong A, Peters C, Noebels JL, Myers RM. Cathepsin B but not cathepsins L or S contributes to the pathogenesis of Unverricht-Lundborg progressive myoclonus epilepsy (EPM1). J Neurobiol 2003;56:315-27.
Houseweart MK, Vilaythong A, Yin XM, Turk B, Noebels JL, Myers RM. Apoptosis caused by cathepsins does not require Bid signaling in an in vivo model of progressive myoclonus epilepsy (EPM1). Cell Death Differ 2003;10:1329-35.
Kantheti P, Diaz ME, Peden AE, Seong EE, Dolan DF, Robinson MS, Noebels JL, Burmeister ML. Genetic and phenotypic analysis of the mouse mutant mh2J, an Ap3d allele caused by IAP element insertion. Mamm Genome 2003;14:157-67.
Noebels JL. How a Sodium Channel Mutation Causes Epilepsy. Epilepsy Curr 2003;3:70-71.
Noebels JL. Exploring new gene discoveries in idiopathic generalized epilepsy. Epilepsia 2003;:16-21.
Noebels JL. The biology of epilepsy genes. Annu Rev Neurosci 2003;26:599-625.
Noebels JL. Stiff Goats, Chloride Ions, and Idiopathic Generalized Epilepsy (IGE). Epilepsy Curr 2003;3:146-147.
Powell EM, Campbell DB, Stanwood GD, Davis C, Noebels JL, Levitt P. Genetic disruption of cortical interneuron development causes region- and GABA cell type-specific deficits, epilepsy, and behavioral dysfunction. J Neurosci 2003;23:622-31.
Qian J, Noebels JL. Topiramate alters excitatory synaptic transmission in mouse hippocampus. Epilepsy Res 2003;55:225-33.
Walz K, Caratini-Rivera S, Bi W, Fonseca P, Mansouri DL, Lynch J, Vogel H, Noebels JL, Bradley A, Lupski JR. Modeling del(17)(p11.2p11.2) and dup(17)(p11.2p11.2) contiguous gene syndromes by chromosome engineering in mice: phenotypic consequences of gene dosage imbalance. Mol Cell Biol 2003;23:3646-55.
Anderson E, Berkovic S, Dulac O, Gardiner M, Jain S, Laue Friis M, Lindhout D, Noebels J, Ottman R, Scaramelli A, Serratosa J, Steinlein O, Avanzini G, Bailey-Wilson J, Cardon L, Fischbach R, Gwinn-Hardy K, Leppert M, Ott J, Lindblad-Toh K, et al.. ILAE genetics commission conference report: molecular analysis of complex genetic epilepsies. Epilepsia 2002;43:1262-7.
Noebels JL. A Gene for JME at Last: The alpha1 GABA Receptor Subunit. Epilepsy Curr 2002;2:131-132.
Noebels JL. Sodium channel gene expression and epilepsy. Novartis Found Symp 2002;241:109-20; discussion 120-3, 226-32.
Noebels JL. Human Epilepsy Can Be Linked to a Defective Calcium Channel. Epilepsy Curr 2002;2:95.
Poolos NP, Das S, Clark GD, Lardizabal D, Noebels JL, Wyllie E, Dobyns WB. Males with epilepsy, complete subcortical band heterotopia, and somatic mosaicism for DCX. Neurology 2002;58:1559-62.
Shahbazian M, Young J, Yuva-Paylor L, Spencer C, Antalffy B, Noebels J, Armstrong D, Paylor R, Zoghbi H. Mice with truncated MeCP2 recapitulate many Rett syndrome features and display hyperacetylation of histone H3. Neuron 2002;35:243-54.
Stables JP, Bertram EH, White HS, Coulter DA, Dichter MA, Jacobs MP, Loscher W, Lowenstein DH, Moshe SL, Noebels JL, Davis M. Models for epilepsy and epileptogenesis: report from the NIH workshop, Bethesda, Maryland. Epilepsia 2002;43:1410-20.
Zhang Y, Mori M, Burgess DL, Noebels JL. Mutations in high-voltage-activated calcium channel genes stimulate low-voltage-activated currents in mouse thalamic relay neurons. J Neurosci 2002;22:6362-71.
Burgess DL, Gefrides LA, Foreman PJ, Noebels JL. A cluster of three novel Ca2+ channel gamma subunit genes on chromosome 19q13.4: evolution and expression profile of the gamma subunit gene family. Genomics 2001;71:339-50.
Heilstedt HA, Burgess DL, Anderson AE, Chedrawi A, Tharp B, Lee O, Kashork CD, Starkey DE, Wu YQ, Noebels JL, Shaffer LG, Shapira SK. Loss of the potassium channel beta-subunit gene, KCNAB2, is associated with epilepsy in patients with 1p36 deletion syndrome. Epilepsia 2001;42:1103-11.
Jacobs MP, Fischbach GD, Davis MR, Dichter MA, Dingledine R, Lowenstein DH, Morrell MJ, Noebels JL, Rogawski MA, Spencer SS, Theodore WH. Future directions for epilepsy research. Neurology 2001;57:1536-42.
Noebels JL. Modeling human epilepsies in mice. Epilepsia 2001;:05-Nov.
Qian J, Noebels JL. Presynaptic Ca2+ channels and neurotransmitter release at the terminal of a mouse cortical neuron. J Neurosci 2001;21:3721-8.
Qiao X, Suri C, Knusel B, Noebels JL. Absence of hippocampal mossy fiber sprouting in transgenic mice overexpressing brain-derived neurotrophic factor. J Neurosci Res 2001;64:268-76.
Zwingman TA, Neumann PE, Noebels JL, Herrup K. Rocker is a new variant of the voltage-dependent calcium channel gene Cacna1a. J Neurosci 2001;21:1169-78.
Ayata C, Shimizu-Sasamata M, Lo EH, Noebels JL, Moskowitz MA. Impaired neurotransmitter release and elevated threshold for cortical spreading depression in mice with mutations in the alpha1A subunit of P/Q type calcium channels. Neuroscience 2000;95:639-45.
Burgess DL, Matsuura T, Ashizawa T, Noebels JL. Genetic localization of the Ca2+ channel gene CACNG2 near SCA10 on chromosome 22q13. Epilepsia 2000;41:24-7.
Burgess DL, Noebels JL. Calcium channel defects in models of inherited generalized epilepsy. Epilepsia 2000;41:1074-5.
Kellaway P, Mizrahi EM, Noebels JL. Benign focal epilepsies of childhood: genetically determined pathophysiology. Report of an international workshop. Epilepsia 2000;41:1049-50.
Lau D, Vega-Saenz de Miera EC, Contreras D, Ozaita A, Harvey M, Chow A, Noebels JL, Paylor R, Morgan JI, Leonard CS, Rudy B. Impaired fast-spiking, suppressed cortical inhibition, and increased susceptibility to seizures in mice lacking Kv3.2 K+ channel proteins. J Neurosci 2000;20:9071-85.
Liu M, Pleasure SJ, Collins AE, Noebels JL, Naya FJ, Tsai MJ, Lowenstein DH. Loss of BETA2/NeuroD leads to malformation of the dentate gyrus and epilepsy. Proc Natl Acad Sci U S A 2000;97:865-70.
Matsuura T, Yamagata T, Burgess DL, Rasmussen A, Grewal RP, Watase K, Khajavi M, McCall AE, Davis CF, Zu L, Achari M, Pulst SM, Alonso E, Noebels JL, Nelson DL, Zoghbi HY, Ashizawa T. Large expansion of the ATTCT pentanucleotide repeat in spinocerebellar ataxia type 10. Nat Genet 2000;26:191-4.
Qian J, Noebels JL. Presynaptic Ca(2+) influx at a mouse central synapse with Ca(2+) channel subunit mutations. J Neurosci 2000;20:163-70.
Steinlein OK, Noebels JL. Ion channels and epilepsy in man and mouse. Curr Opin Genet Dev 2000;10:286-91.
Burgess DL, Biddlecome GH, McDonough SI, Diaz ME, Zilinski CA, Bean BP, Campbell KP, Noebels JL. beta subunit reshuffling modifies N- and P/Q-type Ca2+ channel subunit compositions in lethargic mouse brain. Mol Cell Neurosci 1999;13:293-311.
Burgess DL, Davis CF, Gefrides LA, Noebels JL. Identification of three novel Ca(2+) channel gamma subunit genes reveals molecular diversification by tandem and chromosome duplication. Genome Res 1999;9:1204-13.
Burgess DL, Noebels JL. Single gene defects in mice: the role of voltage-dependent calcium channels in absence models. Epilepsy Res 1999;36:111-22.
Burgess DL, Noebels JL. Voltage-dependent calcium channel mutations in neurological disease. Ann N Y Acad Sci 1999;868:199-212.
Clark GD, Noebels JL. Cortin disaster: lissencephaly genes spell double trouble for the developing brain. Ann Neurol 1999;45:141-2.
Hartmann HA, Colom LV, Sutherland ML, Noebels JL. Selective localization of cardiac SCN5A sodium channels in limbic regions of rat brain. Nat Neurosci 1999;2:593-5.
Noebels JL. Single-gene models of epilepsy. Adv Neurol 1999;79:227-38.
Sutherland ML, Williams SH, Abedi R, Overbeek PA, Pfaffinger PJ, Noebels JL. Overexpression of a Shaker-type potassium channel in mammalian central nervous system dysregulates native potassium channel gene expression. Proc Natl Acad Sci U S A 1999;96:2451-5.
Jiang YH, Armstrong D, Albrecht U, Atkins CM, Noebels JL, Eichele G, Sweatt JD, Beaudet AL. Mutation of the Angelman ubiquitin ligase in mice causes increased cytoplasmic p53 and deficits of contextual learning and long-term potentiation. Neuron 1998;21:799-811.
Kantheti P, Qiao X, Diaz ME, Peden AA, Meyer GE, Carskadon SL, Kapfhamer D, Sufalko D, Robinson MS, Noebels JL, Burmeister M. Mutation in AP-3 delta in the mocha mouse links endosomal transport to storage deficiency in platelets, melanosomes, and synaptic vesicles. Neuron 1998;21:111-22.
Nahm WK, Noebels JL. Nonobligate role of early or sustained expression of immediate-early gene proteins c-fos, c-jun, and Zif/268 in hippocampal mossy fiber sprouting. J Neurosci 1998;18:9245-55.
Noebels JL. Ion Channelopathies and Heritable Epilepsy. News Physiol Sci 1998;13:255-256.
Pennacchio LA, Bouley DM, Higgins KM, Scott MP, Noebels JL, Myers RM. Progressive ataxia, myoclonic epilepsy and cerebellar apoptosis in cystatin B-deficient mice. Nat Genet 1998;20:251-8.
Westenbroek RE, Bausch SB, Lin RC, Franck JE, Noebels JL, Catterall WA. Upregulation of L-type Ca2+ channels in reactive astrocytes after brain injury, hypomyelination, and ischemia. J Neurosci 1998;18:2321-34.
Burgess DL, Jones JM, Meisler MH, Noebels JL. Mutation of the Ca2+ channel beta subunit gene Cchb4 is associated with ataxia and seizures in the lethargic (lh) mouse. Cell 1997;88:385-92.
Cattanach BM, Barr JA, Beechey CV, Martin J, Noebels J, Jones J. A candidate model for Angelman syndrome in the mouse. Mamm Genome 1997;8:472-8.
Cox GA, Lutz CM, Yang CL, Biemesderfer D, Bronson RT, Fu A, Aronson PS, Noebels JL, Frankel WN. Sodium/hydrogen exchanger gene defect in slow-wave epilepsy mutant mice. Cell 1997;91:139-48.
Di Pasquale E, Keegan KD, Noebels JL. Increased excitability and inward rectification in layer V cortical pyramidal neurons in the epileptic mutant mouse Stargazer. J Neurophysiol 1997;77:621-31.
Kash SF, Johnson RS, Tecott LH, Noebels JL, Mayfield RD, Hanahan D, Baekkeskov S. Epilepsy in mice deficient in the 65-kDa isoform of glutamic acid decarboxylase. Proc Natl Acad Sci U S A 1997;94:14060-5.
Noebels JL, Qiao X, Nahm WK. Neurogenetic approaches to axon sprouting in the hippocampus. Adv Neurol 1997;72:35-44.
Noebels JL. Targeting epilepsy genes. Neuron 1996;16:241-4.
Noebels JL, Sutherland ML, Nahm WK, DiPasquale E. Molecular and cellular plasticity in developing epileptic brain. Cold Spring Harb Symp Quant Biol 1996;61:319-26.
Qiao X, Hefti F, Knusel B, Noebels JL. Selective failure of brain-derived neurotrophic factor mRNA expression in the cerebellum of stargazer, a mutant mouse with ataxia. J Neurosci 1996;16:640-8.
Sutherland ML, Delaney TA, Noebels JL. Glutamate transporter mRNA expression in proliferative zones of the developing and adult murine CNS. J Neurosci 1996;16:2191-207.
Chafetz RS, Nahm WK, Noebels JL. Aberrant expression of neuropeptide Y in hippocampal mossy fibers in the absence of local cell injury following the onset of spike-wave synchronization. Brain Res Mol Brain Res 1995;31:111-21.
Noebels JL. Single locus mutations in mice expressing generalized spike-wave absence epilepsies. Ital J Neurol Sci 1995;16:107-11.
Sutherland ML, Delaney TA, Noebels JL. Molecular characterization of a high-affinity mouse glutamate transporter. Gene 1995;162:271-4.
Wang H, Allen ML, Grigg JJ, Noebels JL, Tempel BL. Hypomyelination alters K+ channel expression in mouse mutants shiverer and Trembler. Neuron 1995;15:1337-47.
Frankel WN, Taylor BA, Noebels JL, Lutz CM. Genetic epilepsy model derived from common inbred mouse strains. Genetics 1994;138:481-9.
Helekar SA, Noebels JL. Analysis of voltage-gated and synaptic conductances contributing to network excitability defects in the mutant mouse tottering. J Neurophysiol 1994;71:10-Jan.
Buckwalter MS, Testa CM, Noebels JL, Camper SA. Genetic mapping and evaluation of candidate genes for spasmodic, a neurological mouse mutation with abnormal startle response. Genomics 1993;17:279-86.
Qiao X, Noebels JL. Developmental analysis of hippocampal mossy fiber outgrowth in a mutant mouse with inherited spike-wave seizures. J Neurosci 1993;13:4622-35.
Wu SM, Qiao X, Noebels JL, Yang XL. Localization and modulatory actions of zinc in vertebrate retina. Vision Res 1993;33:2611-6.
Helekar SA, Noebels JL. A burst-dependent hippocampal excitability defect elicited by potassium at the developmental onset of spike-wave seizures in the Tottering mutant. Brain Res Dev Brain Res 1992;65:205-10.
Westenbroek RE, Noebels JL, Catterall WA. Elevated expression of type II Na+ channels in hypomyelinated axons of shiverer mouse brain. J Neurosci 1992;12:2259-67.
Helekar SA, Noebels JL. Synchronous hippocampal bursting reveals network excitability defects in an epilepsy gene mutation. Proc Natl Acad Sci U S A 1991;88:4736-40.
Noebels JL. Mutational analysis of spike-wave epilepsy phenotypes. Epilepsy Res Suppl 1991;4:201-12.
Noebels JL, Marcom PK, Jalilian-Tehrani MH. Sodium channel density in hypomyelinated brain increased by myelin basic protein gene deletion. Nature 1991;352:431-4.
Qiao XX, Noebels JL. Genetic and phenotypic heterogeneity of inherited spike-wave epilepsy: two mutant gene loci with independent cerebral excitability defects. Brain Res 1991;555:43-50.
Noebels JL, Qiao X, Bronson RT, Spencer C, Davisson MT. Stargazer: a new neurological mutant on chromosome 15 in the mouse with prolonged cortical seizures. Epilepsy Res 1990;7:129-35.
Noebels JL, Rutecki PA. Altered hippocampal network excitability in the hypernoradrenergic mutant mouse tottering. Brain Res 1990;524:225-30.
Noebels JL, Sidman RL. Persistent hypersynchronization of neocortical neurons in the mocha mutant of mouse. J Neurogenet 1989;6:53-6.
Noebels JL. Mutational analysis of inherited epilepsies. Adv Neurol 1986;44:97-113.
Noebels JL. Isolating single genes of the inherited epilepsies. Ann Neurol 1984;:S18-21.
Noebels JL. A single gene error of noradrenergic axon growth synchronizes central neurones. Nature 1984;310:409-11.
Levitt P, Noebels JL. Mutant mouse tottering: selective increase of locus ceruleus axons in a defined single-locus mutation. Proc Natl Acad Sci U S A 1981;78:4630-4.
Noebels JL. Analysis of inherited epilepsy using single locus mutations in mice. Fed Proc 1979;38:2405-10.
Noebels JL, Sidman RL. Inherited epilepsy: spike-wave and focal motor seizures in the mutant mouse tottering. Science 1979;204:1334-6.
Noebels JL, Prince DA. Development of focal seizures in cerebral cortex: role of axon terminal bursting. J Neurophysiol 1978;41:1267-81.
Noebels JL, Prince DA. Excitability changes in thalamocortical relay neurons during synchronous discharges in cat neocortex. J Neurophysiol 1978;41:1282-96.
Noebels JL, Roth WT, Kopell BS. Cortical slow potentials and the occipital EEG in congenital blindness. J Neurol Sci 1978;37:51-8.
Noebels JL, Pedley TA. Anatomic localization of topically applied [14C]penicillin during experimental focal epilepsy in cat neocortex. Brain Res 1977;125:293-303.
Noebels JL, Prince DA. Presynaptic origin of penicillin after discharges at mammalian nerve terminals. Brain Res 1977;138:59-74.
Schwartzkroin PA, Futamachi KJ, Noebels JL, Prince DA. Transcallosal effects of a cortical epileptiform focus. Brain Res 1975;99:59-68.

Contact Information

Jeffrey L. Noebels, M.D., Ph.D.
Department of Neurology
Baylor College of Medicine
One Baylor Plaza, MS NB302
Houston, Texas 77030

Tel: 713-798-5860
Fax: 713-798-3771
Email: