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Geoffrey Winston Abbott

Vice Chair, Pharmacology
School of Medicine

Professor, Pharmacology
School of Medicine

Joint Appointment, Physiology and Biophysics


Ph.D., University of London, UK, 1997, Biochemistry


M.S., University of Leicester, UK, 1993, Molecular Pathology and Toxicology (with Distinction)


B.S., University of Durham, UK, 1991, Zoology (Honours)

Phone: (949) 824-3269, 3127
Fax: (949) 824-4855
Email: abbottg@uci.edu

University of California, Irvine
School of Medicine
Department of Pharmacology
360A Med Surge II
Mail Code: 4625
Irvine, CA 92697

picture of Geoffrey Winston Abbott

Research
Interests
ion channel, KCNE, molecular pharmacology, epithelial biology, cardiac arrhythmias
   
URLs Pharmacology Home Page
   
Dr. Abbott's Lab
   
See below for selected publications or click here for additional publication listings available via PUB MED
   
Academic
Distinctions
1997-1999, Wellcome Trust Prize Traveling Postdoctoral Fellowship
2002, Winner, 11th Annual Dept. of Medicine Investigator Award, WCMC
2006, Finalist, 15th Annual Dept. of Medicine Investigator Award, WCMC
2009, Winner, 18th Annual Dept. of Medicine Investigator Award, WCMC
2010-2014, The Irma T. Hirschl Career Scientist Award
2013, Conference Chair, FASEB Science Research Conference on Ion Channel Regulation, Nassau, Bahamas
2013-2015, Chair, Biochemistry and Biophysics of Membranes (BBM) NIH Study Section
   
Research
Abstract
Research in Dr. Abbott’s lab is focused on elucidating the molecular basis for ion channel and transporter physiology and pathophysiology. One of the main directions of the lab has been to define the roles of the KCNE gene family of ion channel subunits, using a combination of techniques including mouse and human genetics, electrophysiology, pharmacology, transcriptomics, and state-of-the-art imaging modalities. Other interests include discovery of novel ion channel subunits and small molecules to modulate ion channel function, and investigation of ion channel trafficking. Abnormal functioning of ion channels can cause disorders including cardiac arrhythmia, epilepsy, myotonia, ataxia, periodic paralysis, hypothyroidism and cancer. We are employing a multidisciplinary approach aimed at understanding the molecular etiologies of, and ultimately developing therapies for, a wide spectrum of “channelopathies” - human diseases arising from ion channel dysfunction.
   
  70. Abbott GW*, Pitt, GS. (2014) Ion channels under the Sun. FASEB Journal 28(5):1957-62 *First and corresponding author

69. Abbott GW*, Tai KK, Neverisky D, Hansler A, Hu Z, Roepke TK, Lerner DJ, Chen Q, Liu L, Zupan B, Toth M, Haynes R, Huang X, Demirbas D, Buccafusca R, Gross SS, Kanda VA and Berry GT. (2014) KCNQ1, KCNE2, and Na+-Coupled Solute Transporters Form Reciprocally Regulating Complexes that Affect Neuronal Excitability. Science Signaling 7(315):ra22. *First and corresponding author

68. Noam Y, Ehrengruber MU, Koh A, Feyen P, Manders EM, Abbott GW, Wadman WJ, Baram TZ. (2014) Filamin A promotes dynamin-dependent internalization of hyperpolarization-activated cyclic nucleotide-gated type 1 (HCN1) channels and restricts Ih in hippocampal neurons. J Biol Chem. 289(9):5889-903

67. Abbott, G.W. (2014) Biology of the KCNQ1 Potassium Channel. New Journal of Science (in press)

66. Abbott G.W. (2014) Pharmacogenetic diversification by alternative translation initiation: background channels to the fore. British Journal of Pharmacology doi: 10.1111/bph.12630. (epub ahead of print)

65. Crump, SM, Abbott, GW. (2014) Arrhythmogenic KCNE gene variants: current knowledge and future challenges. Frontiers in Genetics. 5:3. doi: 10.3389/fgene.2014.00003

64. Hu Z, Kant R, Anand M, King EC, Krogh-Madsen T, Christini DJ, Abbott GW. (2014) Kcne2 Deletion Creates a Multisystem Syndrome Predisposing to Sudden Cardiac Death. Circulation: Cardiovascular Genetics. doi: 10.1161/CIRCGENETICS.113.000315

63. Hu, Z., Crump, S.M., Anand, M., Kant, R., Levi, R., Abbott, G.W. (2014) Kcne3 deletion initiates extracardiac arrhythmogenesis. FASEB Journal epub fj.13-241828

62. Kant, R., Hu, Z., Malhotra, J.K., Krogh-Madsen, T., Christini, D.J., Heerdt, P.M., Abbott, G.W. (2013) NHE isoform swiching and KChIP2 upregulation in aging porcine atria. PLoS One 8(12):e82951. doi: 10.1371/journal.pone.0082951.

61. Hu ZY, Abbott GW, Fang YD, Huang YS, Liu J. (2013) Emulsified isoflurane postconditioning produces cardioprotection against myocardial ischemia-reperfusion injury in rats. J Physiol Sci. 63(4):251-61

60. Abbott, G.W. (2013) KCNE genetics and pharmacogenomics in cardiac arrhythmias: much ado about nothing? Expert Reviews in Clinical Pharmacology. 6(1):49-60

59. Heerdt PM, Kant R, Hu Z, Kanda VA, Christini DJ, Malhotra JK, Abbott GW. (2012) Transcriptomic analysis reveals atrial KCNE1 down-regulation following lung lobectomy. J Mol Cell Cardiol. 53(3):350-3

58. Purtell K, Paroder-Belenitsky M, Reyna-Neyra A, Nicola JP, Koba W, Fine E, Carrasco N, Abbott GW. (2012) The KCNQ1-KCNE2 K+ channel is required for adequate thyroid I- uptake. FASEB J. 26(8):3252-9

57. Krogh-Madsen T, Abbott GW, Christini DJ. (2012) Effects of electrical and structural remodeling on atrial fibrillation maintenance: a simulation study. PLoS Comput Biol. 8(2):e1002390.

56. Kanda V.A., Abbott G.W. (2012) KCNE Regulation of K+ Channel Trafficking - a Sisyphean Task? Front Physiol. 3:231.

55. Abbott G.W.*, Ramesh B., Srai S.K. (2012) Interaction between Soluble and Membrane-Embedded Potassium Channel Peptides Monitored by Fourier Transform Infrared Spectroscopy. PLoS One. 7(11):e49070. doi: 10.1371/journal.pone.0049070 *First and corresponding author

54. Ying SW, Kanda VA, Hu Z, Purtell K, King EC, Abbott GW, Goldstein PA (2012) Targeted Deletion of Kcne2 Impairs HCN Channel Function in Mouse Thalamocortical Circuits. PLoS One 7(8): e42756

53. Abbott GW. (2012) KCNE2 and the K+ channel: The tail wagging the dog. Channels 6(1) http://dx.doi.org/10.4161/chan.19126

52. Roepke, TK, Kanda, VA, Purtell, K, King, EC, Lerner, DJ, Abbott, G.W. (2011) KCNE2 forms potassium channels with KCNA3 and KCNQ1 in the choroid plexus epithelium. FASEB J. 25(12):4264-73

51. Roepke, T.K., King, E.C., Purtell, K., Kanda, V.A., Lerner, D.J., Abbott, G.W. (2011) Genetic dissection reveals unexpected influence of beta subunits on KCNQ1 K+ channel polarized trafficking in vivo. FASEB J. 25(2):727-36

50. Kanda VA, Lewis A, Xu X, Abbott G.W. (2011) KCNE1 and KCNE2 inhibit forward trafficking of homomeric N-type voltage-gated potassium channels. Biophys J. 101(6):1354-63

49. Kanda VA, Lewis A, Xu X, Abbott G.W. (2011) KCNE1 and KCNE2 provide a checkpoint governing voltage-gated potassium channel subunit composition. Biophys J. 101(6):1364-75

48. Kanda, VA, Purtell, K, Abbott, G.W. (2011) Protein Kinase C downregulates IKs by stimulating KCNQ1-KCNE1 potassium channel endocytosis. Heart Rhythm 8(10):1641-7.

47. Purtell, K., Roepke, T.K., Abbott, G.W. (2010) Cardiac arrhythmia and thyroid dysfunction: a novel genetic link. International Journal of Biochemistry and Cell Biology 42(11): 1767-70

46. Harkcom, W., Abbott, G.W. (2010) Emerging concepts in the pharmacogenomics of arrhythmias: ion channel trafficking. Expert Review of Cardiovascular Therapy 8(8):1161-73

45. Roepke, T.K., Purtell, K., King, E.C., La Perle, K.M.D., Lerner, D.J., Abbott, G.W. (2010) Targeted deletion of Kcne2 causes gastritis cystica profunda and gastric neoplasia. PLoS One 5(7):e11451, 1-10

44. Choi, E., Abbott, G.W. (2010) A shared mechanism for lipid- and beta-subunit-coordinated stabilization of the activated K+ channel voltage sensor. FASEB J. 24(5):1518-24

43. Roepke, T.K., King, E.C., Reyna-Neyra, A., Paroder, M., Purtell, K., Koba, W., Fine, E., Lerner, D.J., Carrasco, N., Abbott, G.W. (2009) Kcne2 deletion uncovers its crucial role in thyroid hormone biosynthesis. Nature Medicine 15(10):1186-94 [Faculty of 1000 Medicine evaluation: http://f1000medicine.com/article/id/1165526/]

42. Abbott, G.W.*, Roepke, T.K. (2009) HERG biosynthesis: the positive influence of negative charge. Am J. Physiol Heart Circ Physiol. 296(5):H1211-2 *First and corresponding author

41. Gaeta, S.A., Bub, G., Abbott, G.W., Christini, D.J. (2009) Dynamical mechanism for subcellular alternans in cardiac myocytes. Circulation Research 105(4):335-42

40. Xu, X., Kanda, V.A., Choi, E., Panaghie, G., Roepke, T.K., Gaeta, S.A., Christini, D.J., Lerner, D.J., Abbott, G.W. (2009) MinK-dependent internalization of the IKs potassium channel. Cardiovascular Research 82(3):430-8

39. McCrossan, Z.A., Roepke, T.K., Lewis, A., Panaghie, G., Abbott, GW. (2009) Regulation of the Kv2.1 Potassium Channel by MinK and MiRP1. J Membr Biol. 228(1):1-14.

38. Abbott, G.W.*, Roepke, T.K. (2008) Pharmacogenetics of drug-induced arrhythmias. Expert Review of Clin. Pharm. 1(1):93-104. *First and corresponding author

37. Yang, L., Soonpaa, M.H., Adler, E.D., Roepke, T.K., Kattman, S.J., Kennedy, M., Henckaerts, E., Bonham, K., Abbott, G.W., Linden, R.M., Field, L.J., Keller, G.M. (2008) Human cardiovascular progenitor cells develop from a KDR+ embryonic-stem-cell-derived population. Nature 453(7194):524-8.

36. Morrey, C., Estephan, R., Abbott, G.W., Levi, R. (2008) Cardioprotective Effect of Histamine H3-Receptor Activation: Pivotal Role of G beta gamma-Dependent Inhibition of Voltage-Operated Ca2+ Channels. J. Pharm. Exp. Ther. 326(3):871-8

35. Roepke, T.K., Kontogeorgis, A., Ovanez, C., Xu, X., Young, J.B., Purtell, K., Goldstein, P.A., Christini, D.J., Peters, N.S., Akar, F.G., Gutstein, D.E., Lerner, D.J., Abbott, G.W. (2008) Targeted deletion of kcne2 impairs ventricular repolarization via disruption of IK,slow1 and Ito,f. FASEB Journal 22:3648-3660.

34. Gordon, E., Panaghie, G., Deng, L., Bee, K.J., Roepke, T.K., Krogh-Madsen, T., Christini, D.J., Ostrer, H., Basson, C.T., Chung, W., Abbott, G.W. (2008) A KCNE2 mutation in a patient with cardiac arrhythmia induced by auditory stimuli and serum electrolyte imbalance. Cardiovascular Research 77(1):98-106

33. Abbott, G.W.*, Ramesh, B., Srai, S.K.S. (2008) Secondary structure of the MiRP1 (KCNE2) potassium channel ancillary subunit. Protein and Peptide Letters 15(1):63-75. *First and corresponding author

32. Panaghie, G., Purtell, K., Tai, K.-K., Abbott, G.W. (2008) Voltage-dependent C-type inactivation in a constitutively open K+ channel. Biophysical Journal 95(6):2759-78

31. Abbott, G.W.*, Xu, X., Roepke, T.K. (2007) Impact of ancillary subunits on ventricular repolarization. The Journal of Electrocardiology 40(6 Suppl):S42-6. *First and corresponding author

30. Choi, E., Abbott, G.W. (2007) The MiRP2-Kv3.4 potassium channel: muscling in on Alzheimer’s disease. Molecular Pharmacology 72(3):499-501

29. Panaghie, G., Abbott, G.W. (2007) The role of S4 charges in voltage-dependent and voltage-independent KCNQ1 potassium channel complexes. The Journal of General Physiology 129(2):121-133

28. Abbott, G.W. (2006) Molecular mechanisms of cardiac voltage-gated potassium channelopathies. Current Pharmaceutical Design 12(28):3631-3644

27. Roepke, T.K., Anantharam, A., Kirchhoff, P., Busque, S.M., Young, J.B., Geibel, J.P., Lerner, D.J., Abbott, G.W. (2006) The KCNE2 potassium channel ancillary subunit is essential for gastric acid secretion. J. Biol. Chem 281(33):23740-23747 [Faculty of 1000 Biology evaluation: http://f1000biology.com/article/id/1047240/evaluation]

26. Gordon, E., Cohen, J.-L., Engel, R., Abbott, G.W. (2006) 1,4-diazabicyclo[2.2.2]octane derivatives: a novel class of voltage-gated potassium channel blockers. Molecular Pharmacology 69(3):718-726

25. Panaghie, G., Abbott, G.W. (2006) The impact of ancillary subunits on small-molecule interactions with voltage-gated potassium channels. Current Pharmaceutical Design 12(18):2285-2302

24. Gordon, E., Roepke, T.K., Abbott, G.W. (2006) Endogenous KCNE Subunits Govern Kv2.1 K+ Channel Activation Kinetics in Xenopus Oocyte Studies. Biophysical Journal 90(4):1223-31

23. Panaghie, G., Tai, K.-K., Abbott, G.W. (2006) Interaction of KCNE subunits with the KCNQ1 K+ channel pore. Journal of Physiology 570 (Pt 3):455-67

22. Roepke, T.K, Abbott, G.W. (2006) Pharmacogenetics and cardiac ion channels. Vascular Pharmacology 44(2):90-106

21. Abbott, G.W., Butler, M.H., & Goldstein, S.A. (2006) Phosphorylation and protonation of neighboring MiRP2 sites: function and pathophysiology of MiRP2-Kv3.4 potassium channels in periodic paralysis. FASEB Journal 20(2):293-301

20. Anantharam A, Abbott GW. (2005) Does hERG coassemble with a beta subunit? Evidence for roles of MinK and MiRP1. Novartis Found Symp. 2005;266:100-12; discussion 112-7, 155-8.

19. Cacheaux, L.P., Topf, N., Tibbs, G.R., Schaefer, U.R., Levi, R., Harrison, N.L., Abbott, G.W., Goldstein, P.A. (2005) Impairment of hyperpolarization-activated, cyclic nucleotide-gated channel function by the intravenous general anesthetic propofol. J. Pharm. Exp. Ther. 315(2):517-25

18. McCrossan, Z.A., Abbott, G.W. (2004) The MinK-Related Peptides. Neuropharmacology. 47(6):787-821

17. Lewis A., McCrossan Z.A., Abbott, G.W. (2004) MinK, MiRP1 and MiRP2 diversify Kv3.1 and Kv3.2 potassium channel gating. J. Biol. Chem. 279:7884-7892

16. Anantharam, A., Markowitz, S.M., Abbott, G.W. (2003) Pharmacogenetic considerations in diseases of cardiac ion channels. J. Pharm. Exp. Ther. 307:831-838

15. Tai, K.-K., McCrossan, Z.A., Abbott, G.W. (2003) Activation of mitochondrial ATP-sensitive potassium channels increases cell viability against rotenone-induced cell death. Journal of Neurochemistry 84:1193-1200

14. McCrossan, Z.A., Lewis, A., Panaghie, G., Jordan, P.N., Christini, D.J., Lerner, D.J., Abbott, G.W. (2003) MinK-related peptide 2 modulates Kv2.1 and Kv3.1 potassium channels in mammalian brain. Journal of Neuroscience 23:8077-8091

13. Anantharam, A., Lewis, A., Panaghie, G., Gordon, E., McCrossan, Z.A., Lerner, D.J., Abbott, G.W. (2003) RNA interference reveals that endogenous Xenopus MinK-related Peptides govern mammalian K+ channel function in oocyte expression studies. J. Biol. Chem. 278:11739-11745

12. Abbott, G.W., Goldstein, S.A.N. (2002) Disease-associated mutations in KCNE potassium channel subunits (MiRPs) reveal promiscuous disruption of multiple currents and conservation of mechanism. FASEB Journal 16: 390-400

11. Abbott, G.W., Butler, M.H., Bendahhou, S., Dalakas, M.C., Ptacek, L.J., Goldstein, S.A.N. (2001) MiRP2 forms potassium channels in skeletal muscle with Kv3.4 and is associated with periodic paralysis. Cell 104:217-231.

10. Abbott GW, Goldstein SA, Sesti F. (2001) Do all voltage-gated potassium channels use MiRPs? Circ Res. 88(10):981-3.

9. Abbott GW, Goldstein SA. (2001) Potassium channel subunits encoded by the KCNE gene family: physiology and pathophysiology of the MinK-related peptides (MiRPs). Mol Interv. 1(2):95-107.

8. Sesti, F., Abbott, G.W., Wei, J., Murray, K.T., Saksena, S., Schwartz, P.J., Priori, S.G., Roden, D.M., George, Jr., A.L., Goldstein, S.A.N. (2000) A common polymorphism associated with antibiotic-induced cardiac arrhythmia . Proc. Nat. Acad. Sci. 97:10613-10618

7. Abbott, G.W., Sesti, F., Splawski, I., Buck, M.E., Lehmann, M.H., Timothy, K.W., Keating, M.T., Goldstein, S.A.N. (1999) MiRP1 forms IKr potassium channels with HERG and is associated with cardiac arrhythmia. Cell 97: 175-187

6. Abbott GW, Goldstein SA. A superfamily of small potassium channel subunits: form and function of the MinK-related peptides (MiRPs). Q Rev Biophys. 31(4):357-98.

5. Abbott, G.W., Mercer, E.A.J., Miller, R.T., Ramesh, B., Srai, S.K.S. (1998) Conformational changes in a mammalian voltage-dependent potassium channel inactivation peptide. Biochemistry 37:1640-1645

4. Abbott, G.W., Bloemendal, M., Van Stokkum, I.H.M., Mercer, E.A.J., Miller, R.T., Sewing, S., Wolters, M., Pongs, O., Srai, S.K.S. (1997) Secondary structure, stability and tetramerisation of recombinant Kv1.1 potassium channel cytoplasmic N-terminal fragment. Biochim. Biophys. Acta 1341:71-78

3. Mercer, E.A.J., Abbott, G.W., Brazier, S., Ramesh, B., Haris, P.I., Srai, S.K.S. (1997) Synthetic putative transmembrane region of minimal potassium channel protein (minK) adopts an alpha-helical conformation in phospholipid membranes. Biochemical Journal 325 (2) 475-9

2. Abbott, G.W., Mercer, E.A.J., Wolters, M., Sewing, S., Pongs, O., Srai, S.K.S. (1995) Structure analysis of a recombinant voltage-gated potassium channel (Kv1.1) N-terminus using FTIR spectroscopy and thermal denaturation. Biochem. Sci. Trans. 23(3):479S

1. Mercer, E.A.J., Abbott, G.W., Ramesh, B., Haris, P.I., Chapman, D., Srai, S.K.S. (1995) Structural characterization of a slowly activating potassium channel (IsK). Biochem. Sci. Trans. 23(3):478S
   
Grants National Heart, Lung & Blood Institute (NHLBI) R01 HL079275, 05/04/10-04/30/15, K+ channel trafficking and modulation by Mink and MiRP1 (Role: P.I.).
   
National Heart, Lung & Blood Institute (NHLBI) R01 HL101190, 04/01/10-03/31/15, Predictive multiscale modeling of atrial fibrillation for therapy development (Christini/Abbott M.P.I.s).
   
National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) R01 DK41544, 09/30/2014-07/31/2018, Molecular Characterization of the Sodium/Iodide Symporter (NIS) (Carrasco/Abbott M.P.I.s).
   
National Heart, Lung & Blood Institute (NHLBI) R01 HL079275-08S1, 12/01/12-04/30/15, Diversity Supplement to K+ channel trafficking and modulation by Mink and MiRP1 (Role: P.I.).
   
Professional
Societies
Biophysical Society
The American Society for Biochemistry and Molecular Biology
American Heart Association
   
Graduate Programs Pharmacological Sciences

Medicinal Chemistry and Pharmacology

Interdepartmental Neuroscience Program

   
   
Link to this profile http://www.faculty.uci.edu/profile.cfm?faculty_id=5869
   
Last updated 12/01/2014