Staff Profile:Professor Philip Strange

Responsibilities:
Areas of Interest:

The group works on G protein coupled receptors aiming to understand their structure and function. We have concentrated on receptors for neurotransmitters, particularly dopamine and serotonin, because of the importance of these as targets for drugs used to treat brain disorders. More recenly we have begun to examine chemokine receptors owing to their role in facilitating the infection of cells by HIV.

Current projects are as follows:

  1. understanding how ligands bind to receptors
  2. understanding receptor/G protein signalling
  3. understanding the mechanism of action of antipsychotic drugs
  4. understanding the actions of chemokines on the chemokine receptor CCR5
  5. understanding the basis and importance of GPCR dimerisation
Research groups / Centres:
Publications:
  1. Gazi L, López-Giménez JF and Strange PG (2002). Formation of oligomers by G-protein-coupled receptors. Curr Op Drug Discov Devel, 5, 756-763.
  2. Mueller A, Kelly E and Strange (2002). Pathways for internalisation and recycling of the chemokine receptor, CCR5. Blood ,99, 785-791.
  3. Mueller A, Mahmoud AG, Goedecke MC, McKeating JA and Strange PG (2002). Pharmacological characterisation of the chemokine receptor, CCR5. Brit J Pharmacol ,135, 1033-1043.
  4. Payne SL, Johansson AM and Strange PG (2002). Mechanisms of ligand binding and efficacy at the human D2(short) dopamine receptor. J Neurochem, 82, 1106-1117.
  5. Strange PG (2002). Mechanisms of inverse agonism at G protein coupled receptors. Trends Pharmacol Sci ,23, 89-95.
  6. Alder JT, Hacksell U and Strange PG (2003). Analysis of molecular determinants of affinity and relative efficacy of a series of R- and S-2-(dipropylamino)tetralins at the 5-HT1A serotonin receptor. Br J Pharmacol, 138, 1129-1139.
  7. Gazi, L., Nickolls, S.A. and Strange, P.G. (2003). Functional coupling of the human dopamine D2 receptor with Gαi1, Gαi2, Gαi3 and Gαo G proteins: evidence for agonist regulation of G protein selectivity. Br. J. Pharmacol, 138, 775-786.
  8. Gazi L, Lopez-Gimenez JF, Rudiger MP and Strange PG (2003). Constitutive oligomerization of human D2 dopamine receptors expressed in Spodoptera frugiperda 9 (Sf9) and in HEK293 cells. Analysis using co-immunoprecipitation and time-resolved fluorescence resonance energy transfer. Eur J Biochem, 270, 3928-3938.
  9. Gazi L, Wurch T, Lopez-Gimenez JF, Pauwels PJ and Strange PG (2003). Pharmacological analysis of a dopamine D2Short:Gαo fusion protein expressed in Sf9 cells. FEBS Lett 545(2-3):155-160.
  10. Nickolls SA and Strange PG (2003). Interaction of the D2short dopamine receptor with G proteins: analysis of receptor/G protein selectivity. Biochem Pharmacol, 65, 1139-1150.
  11. Page NM, Bell NJ, Gardiner SM, Manyonda IT, Brayley KJ, Strange PG and Lowry PJ (2003). Characterization of the endokinins: human tachykinins with cardiovascular activity. Proc Natl Acad Sci USA 100(10): 6245-6250.
  12. Akam E and Strange PG (2004). Inverse agonist properties of atypical antipsychotic drugs. Biochem Pharmacol 67(11):2039-2045.
  13. Bakker RA, Dees G, Carrillo JJ, Booth RG, Lopez-Gimenez JF, Milligan G, Strange PG and Leurs R (2004). Domain swapping in the human histamine H1 receptor. J Pharmacol Exp Ther 311(1):131-138
  14. Bartfai T, Benovic JL, Bockaert J, Bond RA, Bouvier M, Christopoulos A, Civelli O, Devi LA, George SR, Inui A, Kobilka B, Leurs R, Neubig R, Pin JP, Quirion R, Roques BP, Sakmar TP, Seifert R, Stenkamp RE and Strange PG (2004). The state of GPCR research in 2004. Nature Reviews Drug Discovery 3(7):574-626
  15. Mueller A and Strange PG (2004). Mechanisms of internalization and recycling of the chemokine receptor, CCR5. Eur J Biochem 271(2): 243-252.
  16. Mueller A and Strange PG (2004). CCL3, acting via the chemokine receptor CCR5, leads to independent activation of Janus kinase 2 (JAK2) and Gi proteins. FEBS Lett 570(1-3):126-132
  17. Mueller A and Strange PG (2004). The chemokine receptor, CCR5. Int J Biochem Cell Biol 36(1):35-38
  18. Nickolls SA and Strange PG (2004). The influence of G protein subtype on agonist action at D2 dopamine receptors. Neuropharmacology 47(6):860-872
  19. Roberts DJ, Lin H and Strange PG (2004). Investigation of the mechanism of agonist and inverse agonist action at D2 dopamine receptors. Biochem Pharmacol 67(9): 1657-1665
  20. Roberts DJ, Lin H and Strange PG (2004). Mechanisms of agonist action at D2 dopamine receptors. Mol Pharmacol 66(6):1573-1579
  21. Roberts DJ and Strange PG (2005). Mechanisms of inverse agonist action at D2 dopamine receptors. Br J Pharmacol 145(1):34-42.
  22. Strange PG (2005). Oligomers of D2 dopamine receptors: evidence from ligand binding. J Mol Neurosci 26(2-3):155-160.
  23. Vivo M and Strange P Cooperativity in ligand binding to deduce receptor-receptor interaction, in G protein coupled receptor-protein interactions, S. George and B. O'Dowd, Editors. 2005, Wiley-Liss: Hoboken, New Jersey. p. 19-36
  24. Lin H, Saisch SG and Strange PG (2006). Assays for enhanced activity of low efficacy partial agonists at the D2 dopamine receptor. Br J Pharmacol 149, 291-299
  25. Mueller A, Mahmoud NG and Strange PG (2006). Diverse signalling by different chemokines through the chemokine receptor CCR5. Biochem Pharmacol 72, 739-748
  26. Vivo M, Lin H and Strange PG (2006). Investigation of cooperativity in the binding of ligands to the D2 dopamine receptor. Mol Pharmacol 69, 226-235
  27. Goggi JL, Sardini A, Egerton A, Strange PG and Grasby PM (2007). Agonist-dependent internalization of D2 receptors: Imaging quantification by confocal microscopy. Synapse 61, 231-241
  28. Haworth B, Lin H, Fidock M, Dorr P and Strange PG (2007). Allosteric effects of antagonists on signalling by the chemokine receptor CCR5. Biochem Pharmacol 74, 891-897
  29. Leach K, Charlton SJ and Strange PG (2007). Analysis of second messenger pathways stimulated by different chemokines acting at the chemokine receptor CCR5. Biochem Pharmacol 74, 881-890
  30. Quirk K, Roberts DJ and Strange PG (2007). Mechanisms of G protein activation via the D2 dopamine receptor: evidence for persistent receptor/G protein interaction after agonist stimulation. Br J Pharmacol 151, 144-152
  31. Strange PG (2007). Mechanisms underlying agonist efficacy. Biochem Soc Trans 35, 733-736
  32. Strange P (2007). Not so good when 75% of grant applications fail. Nature 448, 22
  33. Strange PG (2008). Agonist binding, agonist affinity and agonist efficacy at G protein-coupled receptors. Br J Pharmacol 153, 1353-1363
  34. Strange PG (2008). Signaling mechanisms of GPCR ligands. Curr Opin Drug Discov Devel 11, 196-202
  35. Strange PG (2008). Antipsychotic drug action: antagonism, inverse agonism or partial agonism. Trends Pharmacol Sci 29, 314-321

Contact Details

Building:
School of Biological Sciences 105 (office) 200 (lab)

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