Faculty Profile

Lynette C. Daws, Ph.D.

Research Interests

The broad area of my research is studying the function and regulation of biogenic amine transporters, including the classical serotonin, dopamine and norepinephrine transporters, as well as more recently identified transporters in brain, such as the organic cation transporters and plasma membrane monoamine transporter. Understanding how these transporters function is important in that they are pivotal in controlling the extracellular concentration of biogenic amines and hence, neurotransmission. Moreover, they are the primary site of action for numerous psychotherapeutic and addictive drugs.

One of my primary research interests relates to the serotonin transporter. In humans, a polymorphism of the gene encoding the serotonin transporter leads to its reduced expression. This polymorphism has been linked to a number of disorders including alcoholism and depression. Moreover, individuals with this polymorphism appear to respond differently to drug treatment. We are using mice with a genetically induced reduction in the density of the serotonin transporter (heterozygote serotonin transporter knockout mice, which express 50% fewer serotonin transporters than the "normal", wild-type mouse) to investigate neuroadaptive changes associated with reduced expression of the transporter. We are further investigating the interaction that occurs between stress, serotonin transporter genotype and predisposition to depression and alcoholism, as well as resistance to commonly prescribed medications for these disorders.

Another major focus of our studies is the mechanism of MDMA ("Ecstasy"), para-methoxyamphetamine, amphetamine and cocaine at the dopamine and serotonin transporters. The acute and long term effects of these drugs on transporter function in vivo are being studied. In addition, we have more recently demonstrated that hormones, such as insulin, can influence the activity of biogenic amine transporters. Importantly, we have found that insulin status dictates responsiveness to certain drugs of abuse as well as antidepressants. Thus, it appears that insulin can profoundly affect reward and mood circuitry in brain. We are currently investigating the mechanism through which this occurs. These data have important implications for understanding the high-comorbidity of depression, eating disorders and drug abuse as well as food "addictions," which may lead to obesity.

On a more fundamental level, we are interested in studying how biogenic amine transporters are regulated by receptors. We are currently investigating the role of the 5-HT1B autoreceptor, alpha-adrenoceptors, adenosine receptors and interleukin1-b receptors in regulating activity of the serotonin transporter and of the D2 autoreceptor in regulating activity of the dopamine transporter.

We implement several state-of-the-art techniques including in vivo high-speed chronoamperometry as well as a variety of neurochemical, molecular and behavioral approaches. Dr. Daws' research group comprises Georgianna Gould (Associate Professor/Research); W. Anthony Owens (Research Scientist), Melissa Vitela (Senior Research Associate), Myrna Herrera-Rosales (Research Associate), Mohamed Basiouny (Research Assistant), Christina George (Research Assistant), Melodi Bowman (graduate student), Valentina Garbarino (graduate student), T. Lee Gilman (post-doctoral fellow), and Audrey Hager (post-doctoral fellow). 

Key Words: Serotonin Transporter; Dopamine Transporter; Norepinephrine Transporter, Organic Cation Transporters, Depression; Stress; Drug Abuse; Eating Disorders; In Vivo Chronoamperometry

 

 

Lab Team

  • Mohamed Basiouny
  • Melodi Bowman
  • Valentina Garbarino
  • Christina George
  • Tracy Lee Gilman
  • Georgianna Gould
  • Audrey Hager
  • Myrna Herrera-Rosales
  • W. Anthony Owens
  • Melissa Vitela
Education B.S. (Honors), Flinders University of South Australia, 1989 Ph.D., Flinders University of South Australia, 1994
Selected Publications

Gasser, P.J., Daws, L.C. (2017) Extending the family: Roles for uptake2 transporters in regulation of monoaminergic signaling. Chemical Neuroanatomy ePub ahead of print, 2017 Oct;83-84:107-108. doi: 10.1016/j.jchemneu.2017.07.009. Epub 2017 Jul 28. No abstract available.

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. European Journal of Medicinal Chemistry 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. Journal of Pharmacology and Experimental Therapeutics 360(1):84-94.