Our lab is interested in deciphering the molecular basis of mood and anxiety disorders. By combining psychiatric genetics, molecular pharmacology and transgenic animal models, we pursue aims focused toward unraveling the role of neurotransmitter system components implicated in these diseases.
Our main goal is to identify novel targets for treatment of these devastating disorders that dramatically impact our health system and quality of life worldwide. One of our current major efforts is to understand the role of novel candidate genes in Obsessive-Compulsive Disorder (OCD) and Bipolar Disorder, and how altered expression levels affect brain circuits at neurochemical and behavioral level.
- Psychiatric Genetics- Our studies search for genetic variability that increases the susceptibility for OCD, Tourette syndrome, epilepsy and schizophrenia. We detect single-nucleotide variations; perform genotyping analysis and functional studies for genetic variants. We are also interested in epigenetic and transcriptome analyses. We follow both classic targets at serotonin and dopamine neurotransmitter systems, as well as novel candidates suggested by large genome-wide association studies (GWAS).
- Behavioral Genetics: Our studies search for the functional, in vivo characterization of novel and previously established candidate genes in anxiety, depression, bipolar disorder and OCD. To this end, we generate rodent models using both transgenic technology and viral technology to manipulate genes in specific neuronal types and/or brain regions. We extensively characterize our rodent models by behavioral phenotyping, biochemical, pharmacological and neurochemical approaches.
In addition, we have a strong collaborative network to use electrophysiological approaches to understand the impact of altered gene expression at synaptic level.
One of our major targets of current interest is SLC1A1, the gene encoding the neuronal-epithelial glutamate transporter EAAT3. We have generated conditional, Cre-mediated EAAT3 KO and EAAT3 ovexpressing mice, as a plausible genetic model of OCD.
We are also very interested in continuing our studies in the 5-HT transporter (SERT) KO mouse, a well-established animal model of increased anxiety-like behavior and prone to develop depressive-like behaviors. Current studies are intended to evaluate specific synaptic alterations in cortex and hippocampus, and to decipher how they can explain some of the altered phenotypes that SERT KO mice exhibit.
- Molecular Pharmacology: We study drug-receptor interactions in monoaminergic targets. We are interested in the exploting the Functional Selectivity (agonist-directed trafficking of receptor stimulus, biased agonism), and in rational drug design of multi-targeted ligands. In this section we collaborate with computational and medicinal chemists and pharmacologists, both nationally and internationally.
- #Moya PR, Wendland JR, Andrews AM, Rubenstein L, Timpano KC, Heiman GA, Tischfield JA, King RA, Ramamoorthy S, McMahon F, Murphy DL (2013) “Common and rare alleles of the serotonin transporter gene, SLC6A4, associated with Tourette disorder” Movement Disorders. 28(9): 1263-70
- #Moya PR, Wendland JR, Salemme J, Fried R, Murphy DL (2013) “miR15a and miR-16 regulate serotonin transporter expression in human placental and rat brain raphe cells” International Journal of Neuropsychopharmacology, 16: 621–629.
- Liu X, Cannon DM, Akula N, Moya PR, Knudsen GM, Arentzen TE, Steele J, Laje G, Drevets WC, McMahon FJ (2011) “A non-synonymous polymorphism in galactose mutarotase (GALM) is associated with serotonin transporter binding potential in the human thalamus: results of a genome-wide association study” Molecular Psychiatry 16(6):584-5.
- Murphy DL and Moya PR (2011) “Human Serotonin Transporter Gene (SLC6A4) variants: Their contributions to understanding pharmacogenomic and other functional G x G and G x E differences in health and disease” Current Opinions in Pharmacology, 11(1):3-10.
- #Moya PR, Murphy DL, McMahon FJ and Wendland JR (2010) “Increased gene expression of Diacylglycerol Kinase Eta in Bipolar Disorder” International Journal of Neuropsychopharmacology 13(8):1127-1128.