ONGOING PROJECTS IN THE LAB INCLUDE:
REGULATION OF SEROTONIN TRANSPORTER FUNCTION BY
G PROTEIN BETA-GAMMA SUBUNITS
My research interests focuses on two main areas: (1) Regulation of brain monoamine transporters by GPCRs and (2) Regulation of monoamine transporters by fatty acids (short chain and PUFAs). Our research efforts use molecular biology methods, proteomics-based approaches, and monoamine transporter functional analyses to examine the issue of higher order organization and protein-protein interactions in the control of monoamine homeostasis associated with the activation of several GPCRs expressed in monoamine neurons, and its consequences in monoamine transporter related-behavior.
My long-term research interests include the study of new regulatory mechanisms of monoamine neurotransmission and how alterations in monoamine homeostasis contribute to human disease (e.g. Parkinson’s disease, depression, anxiety, attention deficit hyperactivity disorder, and drug addiction). I am particularly interested in learning how different G protein-coupled receptors signaling pathways modulate the function of brain monoamine transporters (DAT, SERT, NET) and how this mechanism influences the development and progression of mental disorders associated to an imbalance in monoamine levels.
Additionally, in collaboration with Dr. Gonzalo Torres from CUNY we have initiated a new line of investigation related with the regulation of serotonin transporter (SERT) by G-protein coupled receptors through a mechanism Gβγ-dependent. Thus, we have evidenced that SERT is a new target of Gβγ signaling. Accordingly, we have observed that activation of Gβγ potentiate amphetamine-induced 5-HT efflux in hippocampal slices, and this efflux is inhibited in the presence of a Gβγ inhibitor. Thus, we hypothesized that the interaction between monoamine transporters (DAT, SERT and NET) and Gβγ promotes the release of monoamines through DAT, SERT and NET. Consequently, these studies will define not only the role that Gβγ plays in the addictive properties of amphetamine and its analogues, but also the contribution of Gβγ to monoamine homeostasis. The long-term goal of my project is to identify novel therapeutic targets that can be used in the treatment of neuropsychiatric disorders, including depression and drug addiction.