Faculty: Ali Salahpour, PhD
General Research Areas: Neuropharmacology, G protein-coupled Receptors, Signal Transduction
The focus of research in the Salahpour lab is to understand dopamine transmission such that it can be modulated by pharmacology for the treatment of neurological and psychiatric conditions. Some of the specific proteins that we work with are the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), tyrosine hydroxylase (TH) and trace amine associated receptor 1 (TAAR1).
We are currently pursuing three primary areas of research focused on dopamine signalling, transmission and homeostasis in vivo.
1- Understanding the mechanistic role of dopamine and exogenous chemicals in neurodegenerative processes such as Parkinson’s disease.
2- In vivo characterisation of dopamine signalling pathways.
3- Development of new therapies for Dopamine Transporter Deficiency Syndrome that increase dopamine transporter expression.
We use both in vitro and in vivo approaches with transgenic mouse models for our studies. Our multidisciplinary experimental approach involves molecular pharmacology, molecular biology, biochemistry and behavioural pharmacology.
Beerepoot P, Lam VM, Salahpour A. Pharmacological Chaperones of the Dopamine Transporter Rescue Dopamine Transporter Deficiency Syndrome Mutations in Heterologous Cells. J Biol Chem. 2016 Oct 14;291(42):22053-22062.
Masoud ST, Vecchio LM, Bergeron Y, Hossain MM, Nguyen LT, Bermejo MK, Kile B, Sotnikova TD, Siesser WB, Gainetdinov RR, Wightman RM, Caron MG, Richardson JR, Miller GW, Ramsey AJ, Cyr M, Salahpour A. Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and l-DOPA reversible motor deficits. Neurobiol Dis. 2015 Feb;74:66-75. doi: 10.1016/j.nbd.2014.10.016.
Lam V, Rodríguez D, Zhang T, Koh EJ, Carlsson J, Salahpour A. Discovery of trace amine-associated receptor 1 ligands by molecular docking screening against a homology model. Med. Chem. Commun., 2015, 6, 2216
Lohr KM, Bernstein AI, Stout KA, Dunn AR, Lazo CR, Alter SP, Wang M, Li Y, Fan X, Hess EJ, Yi H, Vecchio LM, Goldstein DS, Guillot TS, Salahpour A, Miller GW. Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo. Proc Natl Acad Sci U S A. 2014 Jul 8;111(27):9977-82. doi: 10.1073/pnas.1402134111.
Vecchio LM, Bermejo MK, Beerepoot P, Ramsey AJ, Salahpour A. N-terminal tagging of the dopamine transporter impairs protein expression and trafficking in vivo. Mol Cell Neurosci. 2014 Jul;61:123-32. doi: 10.1016/j.mcn.2014.05.007.
Medvedev IO, Ramsey AJ, Masoud ST, Bermejo MK, Urs N, Sotnikova TD, Beaulieu JM, Gainetdinov RR, Salahpour A. D1 dopamine receptor coupling to PLCβ regulates forward locomotion in mice. J Neurosci. 2013 Nov 13;33(46):18125-33. doi: 10.1523/JNEUROSCI.2382-13.2013.
Lam VM, Beerepoot P, Angers S, Salahpour A. A novel assay for measurement of membrane-protein surface expression using a β-lactamase. Traffic. 2013 Jul;14(7):778-84. doi: 10.1111/tra.12073.
Salahpour A, Espinoza S, Masri B, Lam V, Barak LS, Gainetdinov RR. BRET biosensors to study GPCR biology, pharmacology, and signal transduction. Front Endocrinol (Lausanne). 2012 Aug 29;3:105. doi: 10.3389/fendo.2012.00105.
Department of Pharmacology and Toxicology
Room 4302, Medical Sciences Building
1 King's College Circle