Harley Kurata

Area of Study / Keywords

Ion channels Electrophysiology Epilepsy Anti-epileptic drugs

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About

Dr. Kurata has been an Associate Professor in Pharmacology at University of Alberta, since 2015. Previously, he was a faculty member at University of British Columbia in the Department of Anesthesiology, Pharmacology, and Therapeutics (Assistant Professor 2009-2014, Associate Professor 2014-2015). Dr. Kurata has been supported by several awards including the NIH K99 Pathway to Independence, Heart and Stroke Foundation of Canada Young Investigator, Michael Smith Foundation of Health Research Scholar, Canadian Institutes of Health Research New Investigator Award, and most recently as the Canadian Society of Pharmacology and Therapeutics Ivan Piafsky Young Investigator Award. Dr. Kurata is the Secretary and Vice President of the Canadian Physiological Society.

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Research

Ion channels are an essential class of proteins that underlie rapid signaling, sensation, and movement in our bodies. These proteins form pores in cell membranes that allow charged ions to pass through and create tiny electrical currents that control cellular activity. Our research program investigates how changes in the function of certain ion channels can lead to diseases, or be targeted to treat certain diseases.

Theme 1: Modulation of voltage-gated potassium channels for the treatment of epilepsy

Epilepsy is a diverse collection of neurological disorders characterized by abnormal electrical activity in the brain leading to seizures. An estimated 50 million people worldwide are affected by some form of epilepsy, and startlingly, 30% of affected individuals are resistant to conventional treatments. We are investigating the detailed mechanism of action of a new class of anti-epileptic drug. Retigabine is the prototypical member of this class, and over the past few years has been approved for use in humans in Europe and North America. Retigabine has a unique mechanism of action: it is the only anti-epileptic drug that activates voltage-gated K+ channels in the brain. We investigate the molecular target of retigabine (KCNQ channels, or ‘M’-channels), and other drugs that are thought to target the voltage-sensing domain of these channels. We hope this work will accelerate the development of new anti-epileptic drugs, and develop our understanding of how mutations in these channels are linked to seizure disorders.

Theme 2: Ion channel regulation in multi-protein complexes

Mutations in the Kv1.2 potassium channel gene have been linked to severe epileptic encephalopathy, highlighting the essential role of this channel in the regulation of electrical activity. We use this as a model system to investigate assembly of ion channels into multi-protein complexes. We recently identified Slc7a5 (LAT1) as a powerful regulator of Kv1.2 expression and activity. This is of great interest to us, because mutations in both Kv1.2 and Slc7a5 are linked to neurological diseases, and manyl epilepsy-linked Kv1.2 mutations exhibit hypersensitivity to the effects of Slc7a5. We are also actively investigating a number of other regulatory mechanisms identified from unbiased mass spectrometry screens of voltage-gated potassium channel complexes.  We hope this work will reveal unrecognized complexity in the organization and regulation of ion channels involved in signal transmission in the brain. 

Yang N.D., Kanyo R., Zhao L., Li J., Kang P.W., Dou A.K., White K.M.F., Shi J., Nerbonne J.M., Kurata H.T., Cui J.

Science Advances. 2022 July; 8 (29)::eabo3625 10.1126/sciadv.abo3625

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Canadian Society of Molecular Biosciences. 2022 April;

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Canadian Society for Molecular Biosciences. 2022 April;

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Canadian Society for Molecular Biosciences. 2022 April;

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Kurata H.T.

JOURNAL OF GENERAL PHYSIOLOGY. 2021 June; 153 (6) 10.1085/jgp.202112929

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Canadian Society of Molecular Biosciences. 2021 June;

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Rodan L.H., Spillmann R.C., Kurata H.T., Lamothe S.M., Maghera J., Jamra R.A., Alkelai A., Antonarakis S.E., Atallah I., Bar-Yosef O., Bilan F., Bjorgo K., Blanc X., Van Bogaert P., Bolkier Y., Burrage L.C., Christ B.U., Granadillo J.L., Dickson P., Donald K.A., Dubourg C., Eliyahu A., Emrick L.T., Engleman K., Gonfiantini M.V., Good J.M., Kalser J., Kloeckner C., Lachmeijer G., Macchiaiolo M., Nicita F., Odent S., O’Heir E., Ortiz-Gonzalez X., Pacio-Miguez M., Palomares-Bralo M., Pena L., Platzer K., Quinodoz M., Ranza E., Rosenfeld J.A., Roulet-Perez E., Santani A., Santos-Simarro F., Pode-Shakked B., Skraban C., Slaugh R., Superti-Furga A., Thiffault I., van Jaabrsveld R.H., Vincent M., Wang H.G., Zacher P., Alejandro M.E., Azamian M.S., Bacino C.A., Balasubramanyam A., Burrage L.C., Chao H.T., Clark G.D., Craigen W.J., Dai H., Dhar S.U., Emrick L.T., Goldman A.M., Hanchard N.A., Jamal F., Karaviti L., Lalani S.R., Lee B.H., Lewis R.A., Marom R., Moretti P.M., Murdock D.R., Nicholas S.K., Orengo J.P., Posey J.E., Potocki L., Rosenfeld J.A., Samson S.L., Scott D.A., Tran A.A., Vogel T.P., Wangler M.F., Yamamoto S., Eng C.M., Liu P., Ward P.A., Behrens E., Deardorff M., Falk M., Hassey K., Sullivan K., Vanderver A., Goldstein D.B., Cope H., McConkie-Rosell A., Schoch K., Shashi V., Smith E.C., Spillmann R.C., Sullivan J.A., Tan Q.K.G., Walley N.M., Agrawal P.B., Beggs A.H., Berry G.T., Briere L.C., Cobban L.A., Coggins M., Cooper C.M., Fieg E.L., High F., Holm I.A., Korrick S., Krier J.B., Lincoln S.A., Loscalzo J., Maas R.L., MacRae C.A., Pallais J.C., Rao D.A., Rodan L.H., Silverman E.K., Stoler J.M., Sweetser D.A., Walker M., Walsh C.A., Esteves C., Kelley E.G., Kohane I.S., LeBlanc K., McCray A.T., Nagy A., Dasari S., Lanpher B.C., Lanza I.R., Morava E., Oglesbee D., Bademci G., Barbouth D., Bivona S., Carrasquillo O., Chang T.C.P., Forghani I., Grajewski A., Isasi R., Lam B., Levitt R., Liu X.Z., McCauley J., Sacco R., Saporta M., Schaechter J., Tekin M., Telischi F., Thorson W., Zuchner S., Colley H.A., Dayal J.G., Eckstein D.J., Findley L.C., Krasnewich D.M., Mamounas L.A., Manolio T.A., Mulvihill J.J., LaMoure G.L., Goldrich M.P., Urv T.K., Doss A.L., Acosta M.T., Bonnenmann C., D’Souza P., Draper D.D., Ferreira C., Godfrey R.A., Groden C.A., Macnamara E.F., Maduro V.V., Markello T.C., Nath A., Novacic D., Pusey B.N., Toro C., Wahl C.E., Baker E., Burke E.A., Adams D.R., Gahl W.A., Malicdan M.C.V., Tifft C.J., Wolfe L.A., Yang J., Power B., Gochuico B., Huryn L., Latham L., Davis J., Mosbrook-Davis D., Rossignol F., Ben Solomon, MacDowall J., Thurm A., Zein W., Yousef M., Adam M., Amendola L., Bamshad M., Beck A., Bennett J., Berg-Rood B., Blue E., Boyd B., Byers P., Chanprasert S., Cunningham M., Dipple K., Doherty D., Earl D., Glass I., Golden-Grant K., Hahn S., Hing A., Hisama F.M., Horike-Pyne M., Jarvik G.P., Jarvik J., Jayadev S., Lam C., Maravilla K., Mefford H., Merritt J.L., Mirzaa G., Nickerson D., Raskind W., Rosenwasser N., Scott C.R., Sun A., Sybert V., Wallace S., Wener M., Wenger T., Ashley E.A., Bejerano G., Bernstein J.A., Bonner D., Coakley T.R., Fernandez L., Fisher P.G., Fresard L., Hom J., Huang Y., Kohler J.N., Kravets E., Majcherska M.M., Martin B.A., Marwaha S., McCormack C.E., Raja A.N., Reuter C.M., Ruzhnikov M., Sampson J.B., Smith K.S., Sutton S., Tabor H.K., Tucker B.M., Wheeler M.T., Zastrow D.B., Zhao C., Byrd W.E., Crouse A.B., Might M., Nakano-Okuno M., Whitlock J., Brown G., Butte M.J., Dell’Angelica E.C., Dorrani N., Douine E.D., Fogel B.L., Gutierrez I., Huang A., Krakow D., Lee H., Loo S.K., Mak B.C., Martin M.G., Martínez-Agosto J.A., McGee E., Nelson S.F., Nieves-Rodriguez S., Palmer C.G.S., Papp J.C., Parker N.H., Renteria G., Signer R.H., Sinsheimer J.S., Wan J., Wang L.k., Perry K.W., Woods J.D., Alvey J., Andrews A., Bale J., Bohnsack J., Botto L., Carey J., Pace L., Longo N., Marth G., Moretti P., Quinlan A., Velinder M. (author list truncated)

GENETICS IN MEDICINE. 2021 June; 10.1038/s41436-021-01232-8

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Kalyaanamoorthy S., Lamothe S.M., Hou X., Moon T.C., Kurata H.T., Houghton M., Barakat K.H.

Scientific Reports. 2020 December; 10 (1) 10.1038/s41598-020-72889-5

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Maghera J., Li J., Lamothe S.M., Braun M., Appendino J.P., Au P.Y.B., Kurata H.T.

Epilepsia Open. 2020 December; 5 (4):562-573 10.1002/epi4.12438

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Lamothe S.M., Sharmin N., Silver G., Satou M., Hao Y., Tateno T., Baronas V.A., Kurata H.T.

eLife. 2020 October; 9 10.7554/eLife.54916

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Satou M., Wang J., Nakano-Tateno T., Teramachi M., Suzuki T., Hayashi K., Lamothe S., Hao Y., Kurata H., Sugimoto H., Chik C., Tateno T.

MOLECULAR AND CELLULAR ENDOCRINOLOGY. 2020 September; 515 10.1016/j.mce.2020.110868