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Neurology

Houston, Texas

The Cullen Building at Baylor College of Medicine.
Department of Neurology
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Jeffrey L. Noebels, M.D., Ph.D.

Professor of Neurology, Neuroscience, and Molecular and Human Genetics [view Neuroscience | Genetics profiles]

Cullen Trust for Health Care Endowed Chair in Neurogenetics

Director, Blue Bird Circle Developmental Neurogenetics Laboratory

Board Certification

American Board of Psychiatry and Neurology, Neurology

Medical School

M.D., Yale University, Conn.

Graduate School

Ph.D., Stanford University, Calif.

Residency

Neurology, Massachusetts General Hospital, Boston, Mass.

Clinical Interests

Epilepsy and inherited neurological disease

Research Interests

The principal research strategy in the Developmental Neurogenetics Laboratory is to apply mutational analysis to learn how genes regulate neuronal excitability and network synchronization within the mammalian central nervous system. Spontaneous and transgenic mutations that express neurological phenotypes in the mouse provide a valuable opportunity to identify excitability genes and examine their role in synaptic plasticity in the developing brain. Brain wave (EEG) phenotypes emerge from altered neuronal signaling properties, and are of special interest. Six mouse mutants causing spike-wave synchronization of the neocortex have been discovered in our laboratory, and four (tottering, lethargic, ducky, and stargazer) are linked to mutations of subunits of neuronal voltage-gated calcium ion channels. Study of these mice have led to the identification of novel members of the gene family, and a new understanding of how related molecules rescue function and determine selective vulnerability within thalamocortical pathways. Other new mouse models for human epilepsy syndromes involving mutant ion channel, receptor, and synaptic vesicle proteins are being analyzed to pinpoint the neural network and specific electrophysiological abnormalities characteristic of the human disorder. We also explore the presynaptic release process and activity-induced changes of downstream gene expression in epileptic brain to identify regulatory pathways that are critical mechanisms of disease progression.

At present, mutant mouse models of inherited disorders in neuronal excitability are under investigation using in vitro cell physiology and optical fluorescence measurements of ion channel activity and exocytosis in presynaptic terminals of mouse brain slices, as well as molecular anatomical techniques including laser-capture microspcopy and realtime quantitative PCR, in situ hybridization and immunohistochemistry, and microarray analysis of seizure-activated mRNAs. These studies form the basis for development of strategies to selectively correct the tissue expression of neuronal gene errors early in development.

In collaboration with the Baylor Human Genome Sequencing Center, a large-scale translational genomic research study examining variants in human ion channel genes is currently in progress. The Human Channelopathy Project will evaluate the contribution of SNP profiles in several hundred ion channel subunit genes to the complex inheritance of neurological excitability disorders such as epilepsy.

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: 713-798-7528
Email:

Journal Publications (Selected out of 153)

  • Klassen T, Davis C, Goldman A, Burgess D, Chen T, Wheeler D, et al. Exome sequencing of ion channel genes reveals complex profiles confounding personal risk assessment in epilepsy. Cell. 2011;145(7):1036-48. [View journal article]
  • Qian J, Xu K, Yoo J, Chen TT, Andrews G, Noebels JL. Knockout of Zn transporters Zip-1 and Zip-3 attenuates seizure-induced CA1 neurodegeneration. J Neurosci. 2011;31(1):97-104. [View journal article]
  • Zhu PJ, Huang W, Kalikulov D, Yoo JW, Placzek AN, Stoica L, et al. Suppression of PKR promotes network excitability and enhanced cognition by interferon-gamma-mediated disinhibition. Cell. 2011;147(6):1384-96. [View journal article]
  • Glasscock E, Yoo JW, Chen TT, Klassen TL, Noebels JL. Kv1.1 potassium channel deficiency reveals brain-driven cardiac dysfunction as a candidate mechanism for sudden unexplained death in epilepsy. J Neurosci. 2010;30(15):5167-75. [View journal article]
  • Ernst WL, Zhang Y, Yoo JW, Ernst SJ, Noebels JL. Genetic enhancement of thalamocortical network activity by elevating alpha 1g-mediated low-voltage-activated calcium current induces pure absence epilepsy. J Neurosci. 2009;29(6):1615-25. [View journal article]
  • Goldman AM, Glasscock E, Yoo J, Chen TT, Klassen TL, Noebels JL. Arrhythmia in heart and brain: KCNQ1 mutations link epilepsy and sudden unexplained death. Sci Transl Med. 2009;1(2):2ra6. [View journal article]
  • Price MG, Yoo JW, Burgess DL, Deng F, Hrachovy RA, Frost JD, et al. A triplet repeat expansion genetic mouse model of infantile spasms syndrome, Arx(GCG)10+7, with Interneuronopathy, spasms in infancy, persistent seizures, and adult cognitive and behavioral impairment. J Neurosci. 2009;29(27):8752-63. [View journal article]
  • Glasscock E, Qian J, Yoo JW, Noebels JL. Masking epilepsy by combining two epilepsy genes. Nat Neurosci. 2007;10(12):1554-8. [View journal article]
  • Palop JJ, Chin J, Roberson ED, Wang J, Thwin MT, Bien-Ly N, et al. Aberrant excitatory neuronal activity and compensatory remodeling of inhibitory hippocampal circuits in mouse models of Alzheimer's disease. Neuron. 2007;55(5):697-711. [View journal article]
  • Qian J, Noebels JL. Visualization of transmitter release with zinc fluorescence detection at the mouse hippocampal mossy fibre synapse. J Physiol. 2005;566(Pt 3):747-58. [View journal article]

Books and Volumes

  • Noebels J, Avoli M, Rogawski M, Olsen R, Delgado-Escueta A, editors. Jasper's basic mechanisms of the epilepsies. 4th ed. New York: Oxford University Press; 2012.
  • Avanzini G, Noebels J, editors. Genetics of epilepsy and genetic epilepsies. Montrouge, France: John Libbey Eurotext; 2009. p. 1-272.
  • Schwartzkroin PA, Moshe SL, Noebels JL, Swann JW, editors. Brain development and epilepsy. New York: Oxford University Press; 1995. p. 1-352.
  • Kellaway P, Noebels JL, editors. Problems and concepts in developmental neurophysiology. The Johns Hopkins series in contemporary medicine and public health. Baltimore: Johns Hopkins University Press; 1989.

Book Chapters and Other Publications

  • Noebels JL. The voltage-gated calcium channel and absence epilepsy. In: Noebels J, Avoli M, Rogawski M, Olsen R, Delgado-Escueta A, editors. Jasper's basic mechanisms of the epilepsies. 4th ed. New York: Oxford University Press; 2012. p. 702-13.
  • Noebels JL. Genes and the biology of complex epilepsy phenotypes. In: Avanzini G, Noebels J, editors. Genetics of epilepsy and genetic epilepsies. Montrouge, France: John Libbey Eurotext; 2009. p. 23-30.

Poster and Platform Presentations (Selected out of 50)

  • Klassen TL, Tomson T, Sveinsson O, von Dobeln U, Drabek J, Noebels J, et al. STOP SUDEP Program: Application of visual automated fluorescence electrophoresis in the qualitative profiling of archived SUDEP samples. Abstract No 1.053, 2013, American Epilepsy Society Annual Meeting, www.aesnet.org.
  • Meyer JF, Maheshwari A, Noebels J, Smirnakis S. In vivo 2-photon confocal microscopy of cortical absence epilepsy. Abstract No 1.102, 2013, American Epilepsy Society Annual Meeting, www.aesnet.org.
  • Bomben VC, Holth JK, Cramer PE, Landreth GE, Noebels JL. Bexarotene decreases hyperexcitability in two mouse models with epilepsy. Program No. 534.02. 2013 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2013. Online.
  • Zhang C, Huang Y-M, Zhu P, Reed JG, Costa-Mattioli M, Noebels JL, et al. Genetic ablation of betaII-spectrin in the central nervous system results in axon degeneration, epilepsy and postnatal lethality. Program No. 721.06. 2013 Neuroscience Meeting Planner. San Diego, CA: Society for Neuroscience, 2013. Online.
  • Bomben V, Holth J, Reed J, Cramer P, Landreth G, Noebels J. Bexarotene reduces network excitability in models of Alzheimer's disease and epilepsy. Presented at the Alzheimer's Association, Houston and Southeast Texas Chapter, 7th Annual Research Symposium on Alzheimer's Disease (Sept. 12, 2013). [View poster]
  • Klassen TL, Chen TT, Reed JG, Kole MJ, Goldman AM, Marini C, et al. Myotonia in brain: 'Skeletal' chloride channel ClC-1 linked to idiopathic generalized epilepsy with focal myotonia. Abstract No 3.312, 2012, American Epilepsy Society Annual Meeting, www.aesnet.org.
  • Ince Dunn G, Okana HJ, Okana H, Jensen K, Park W-Y, Mele A, et al. Neuronal Elavl proteins regulate RNA splicing and abundance to control brain glutaminase expression and neuronal excitability. Program No. 136.09. 2012 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2012. Online.
  • Maheshwari A, Reed JG, Noebels JL. Dendritic AMPA receptor deficit on cortical interneurons in the stargazer mouse model of absence epilepsy. Abstract No 1.013, 2011, American Epilepsy Society Annual Meeting, www.aesnet.org
  • Glasscock E, Qian J, Kole MJ, Noebels JL. Flupirtine reverses hyperexcitability in Kv1.1 potassium channel deficient myelinated vagal axons. Program No. 138.23. 2011 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2011. Online.
  • Holth J, Reed JG, Inoue T, Pautler R, Botas J, Noebels J. Tau loss regulates excitability in mouse and Drosophila genetic models of epilepsy. Program No. 671.08. 2011 Neuroscience Meeting Planner. Washington, DC: Society for Neuroscience, 2011. Online.

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