Dr. Lynette Daws' research focuses on the function and regulation of biogenic amine transporters, including “classic” serotonin, dopamine and norepinephrine transporters, as well as organic cation and plasma membrane monoamine transporters; transporters that were recently identified as important regulators of central biogenic amine neurotransmission. These transporters are crucial for controlling concentrations of extracellular biogenic amines and therefore, the strength and duration of biogenic amine neurotransmission. Moreover, these transporters are primary sites of action for numerous psychotherapeutic and addictive drugs.
Our lab utilizes an integrative and translational approach, including in vivo neurochemistry, behavior, in vitro biochemistry and cell culture, to understand how these transporters contribute to the etiology of psychiatric disease and how they may be harnessed as targets for improved therapeutic intervention.
Samboa, D., Lin, M., Owens, W.A., Richardson, B., Jagnarine, D.A., Madhur, S., Alonge, T., Ali, M., Katz, J., Febo, M., Henry, K., Bruijnzeel, A.W., Daws, L.C., Khoshbouei, K. (in press) Sigma-1 receptor regulation of dopamine neurotransmission: beyond the surface membrane. Nat. Comm. In press.
Krause-Heuer, A.M.,† Fraser-Spears, R.†, Dobrowolski, J., Ashford, M.E., Wyatt, N.A., Roberts, M.P., Gould, G.G., Cheah, W-C., Ng, C., Bhadbhade, M., Zhang, B., Greguric, I., Wheate, N.J., Kumar, N., Koek, W., Callaghan, P.D., Daws, L.C*., Fraser, B.H.* (2017) Evaluation of the antidepressant therapeutic potential of isocyanine and pseudoisocyanine analogues of the organic cation decynium-22. Eur. J. Med. Chem. 137:476-487. * co-corresponding authors, contributed equally; † co-first authors
Mitchell, N.C., Bowman, M.A., Gould, G.G., Koek, W., Daws, L.C. (2017) Ontogeny of NET expression and antidepressant-like response to desipramine in wild-type and SERT mutant mice. J. Pharmacol. Exp. Ther. 360(1):84-94.
Mitchell, N.C., Owens, W.A.,Vitela, M., Gould, G., Koek, W.,Daws, L.C. (2016) Ontogeny of SERT expression and antidepressant-like response to escitalopram in wild-type and SERT mutant mice. J. Pharmacol. Exp. Ther. 358(2):271-281.
Montañez S, Munn
JL, Owens WA, Horton RE, Daws LC. 5-HT1B
receptor modulation of the serotonin transporter in vivo: studies using KO
mice. Neurochem Int. 2014 Jul;73:127-31. doi:
10.1016/j.neuint.2013.11.004. Epub 2013 Nov 15.
Mitchell NC, Gould GG, Smolik CM, Koek W, Daws LC. Antidepressant-like drug effects in juvenile and adolescent mice in the tail suspension test: Relationship with hippocampal serotonin and norepinephrine transporter expression and function.Front Pharmacol. 2013 Oct 28;4:131.
Horton RE, Apple DM, Owens WA, Baganz NL, Cano S, Mitchell NC, Vitela M, Gould GG, Koek W, Daws LC. Decynium-22 enhances SSRI-induced antidepressant-like effects in mice: uncovering novel targets to treat depression. J Neurosci. 2013 Jun 19;33(25):10534-43.
Baganz N, Horton R, Martin K, Holmes A, Daws LC. Repeated swim impairs serotonin clearance via a corticosterone-sensitive mechanism: organic cation transporter 3, the smoking gun. J Neurosci. 2010 Nov 10;30(45):15185-95.
Baganz NL, Horton RE, Calderon AS, Owens WA, Munn JL, Watts LT, Koldzic-Zivanovic N, Jeske NA, Koek W, Toney GM, Daws LC. Organic cation transporter 3: Keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice. Proc Natl Acad Sci U S A. 2008 Dec 2;105(48):18976-81.
Owens WA, Williams JM, Saunders C, Avison MJ, Galli A, Daws LC. Rescue of dopamine transporter function in hypoinsulinemic rats by a D2 receptor-ERK-dependent mechanism. J Neurosci. 2012 Feb 22;32(8):2637-47.