Associate Professor - Department of Neurology Associate Professor - Department of Neuroscience M.D., Yale, 1990 Ph.D., (Cellular and Molecular Physiology) Yale, 1991 Baylor College of Medicine, Mailstop NB-302 One Baylor Plaza Houston TX 77030 Telephone: 713-798-4939 - Fax: 713-798-3464 Email: ecc1@bcm.edu

As a laboratory-based researcher and clinical neurologist, I believe in the synergy of basic and translational studies of brain function.  Basic mechanistic insights provide needed tools for creating new treatments, preventative interventions and cures to disease; careful study of disease is an extraordinarily powerful approach for uncovering totally unexpected but important new brain mechanisms.

My lab conducts both basic and translational research of ion channels, cellular excitability, and epilepsy.  We have focused on KCNQ channels, a novel subfamily among the nearly 100 subunits for potassium channels.  Disease phenotypes put a spotlight on KCNQ channels: KCNQ1 mutations cause heart arrhythmia and sudden death, KCNQ2 and KCNQ3 mutations cause epilepsy with a distinctive developmental time course, and KCNQ4 causes deafness (Cooper and Jan, 1989).  Noting that KCNQ2 mutations can cause the peripheral nerve symptom, myokymia, we discovered that both KNQ2 and KCNQ3 colocalize with voltage-dependent sodium (NaV) channels on axons and thereby modulate the initiation and conduction of action potentials (Devaux et al., 2004).   KCNQ and NaV channels possess anchor motifs allowing them to be concentrated by a specialized cytoskeleton at nodes of Ranvier and axon initial segments (Pan et. al., 2006). The KCNQ2/3 and NaV anchor motifs are very similar in sequence, underlining the importance of the two channel types’ physical and functional interaction, but these issues remain to be further elucidated.  We showed that KCNQ2 and KCNQ3 were vertebrate novelties that evolved in concert with myelin and saltatory conduction (Hill et al., 2008).    We have worked to develop KCNQ openers as treatments for epilepsy in neonates and status epilepticus (Raol et al., 2009).

Current projects include interdisciplinary studies of KCNQ channel protein complexes using proteomic approaches, molecular biology, and both mammalian and non-mammalian models.  We are performing pharmacological studies of KCNQ openers, and studies of mutant mice with alterations in genes for KCNQ channels and their interacting proteins.  Other key technical approaches include patch clamp electrophysiology, immunofluorescence microscopy, computational modeling, and molecular phylogenetics.  Positions are currently available for students and post-doctoral fellows.  Highly motivated individuals interested in participating are encouraged to contact Dr. Cooper.

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Cooper EC Made for anchorin’: Made for "anchorin": Kv7.2/7.3 (KCNQ2/KCNQ3) channels and the modulation of neuronal excitability in vertebrate axons. Semin Cell Dev Biol. 2011;22:185-92.

Raol YH, Lapides DA, Keating JG, Brooks-Kayal AR, Cooper EC. A KCNQ channel opener for experimental neonatal seizures and status epilepticus. Ann Neurol. 2009;65:326-36.

Hill AS, Nishino A, Nakajo K, Zhang G, Fineman JR, Selzer ME, Okamura Y, Cooper EC. Ion channel clustering at the axon initial segment and node of Ranvier evolved sequentially in early chordates. PLoS Genet. 2008;4:e1000317.

Shah MM, Migliore M, Valencia I, Cooper EC, Brown DA. Functional significance of axonal Kv7 channels in hippocampal pyramidal neurons. Proc Natl Acad Sci U S A. 2008;105:7869-74.

Pan Z, Kao T, Horvath Z, Lemos J, Sul JY, Cranstoun SD, Bennett V, Scherer SS, Cooper EC. A common ankyrin-G-based mechanism retains KCNQ and NaV channels at electrically active domains of the axon. J Neurosci. 2006;26:2599-613.

Schwarz JR, Glassmeier G, Cooper EC, Kao TC, Nodera H, Tabuena D, Kaji R, Bostock H. KCNQ channels mediate IKs, a slow K+ current regulating excitability in the rat node of Ranvier. J Physiol. 2006;573:17-34.

Surti TS, Huang L, Jan YN, Jan LY, Cooper EC. Identification by mass spectrometry and functional characterization of two phosphorylation sites of KCNQ2/KCNQ3 channels. Proc Natl Acad Sci U S A. 2005;102:17828-33.

Devaux JJ, Kleopa KA, Cooper EC, Scherer SS. KCNQ2 is a nodal K+ channel. J Neurosci. 2004;24:1236-44.

Cooper EC, Jan LY. M-channels: neurological diseases, neuromodulation, and drug development. Arch Neurol. 2003;60:496-500.

Cooper EC, Harrington E, Jan YN, Jan LY. M channel KCNQ2 subunits are localized to key sites for control of neuronal network oscillations and synchronization in mouse brain. J Neurosci. 2001;21:9529-40.

Cooper EC, Aldape KD, Abosch A, Barbaro NM, Berger MS, Peacock WS, Jan YN, Jan LY. Colocalization and coassembly of two human brain M-type potassium channel subunits that are mutated in epilepsy. Proc Natl Acad Sci U S A. 2000;97:4914-9.

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Human Frontiers Science Program Fellowship

Clinical Investigator Development Award - NINDS

Pfizer Postdoctoral Fellowship in Neuroscience

American Academy of Neurology Young Investigator Award in Epilepsy Research

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• Baouyen Tran (Neuroscience)

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KCNQ subunits are highly expressed at axon initial segments (AIS) of hippocampal CA1 pyramidal and cerebellar purkinje neurons. A. Cartoon of neuronal subcellular domains. B. Schematic indicating that the AP occurs first at the distal portion of the AIS, then propagates bidirectionally into the somatodendritic and distal axonal domains. C. Immunostained cerebellar section, showing intense colabeling of two Purkinje cell AIS by antibodies against voltage-gated Na+ channels (red in C, grayscale in D) and KCNQ2 (green in D, grayscale in E). F. Hippocampal CA1 tissue section immunostained for KCNQ2 (green). Strong KCNQ2 staining of pyramidal cell AIS is apparent at the stratum pyramidale (s. pyr.) – stratum oriens (s. or.) border. In C and F, Purkinje, granule, and pyramidal cell nuclei are stained blue using DAPI.

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