Western Australian Institute for Medical Research (WAIMR)


http://www.waimr.uwa.edu.au

Associate Professor Kevin Pfleger

Kevin Pfleger

Associate Professor Pfleger is head of the Laboratory for Molecular Endocrinology - GPCRs, which is a world leader in its field, having developed technology which places special light-emitting labels on proteins of interest, allowing interactions between proteins to be studied. Advances demonstrated by Kevin and the laboratory now enable these interactions to be monitored in real-time in living cells for time periods beyond those previously possible. Kevin's work focuses heavily on G-protein coupled receptors, which are proteins that enable cells to respond to particular hormones in an appropriate manner.

Kevin studied Natural Sciences (Pharmacology) at Cambridge University in the UK and obtained his PhD in Molecular Endocrinology, graduating from the College of Medicine and Veterinary Medicine, University of Edinburgh where he had a Medical Research Council Postgraduate Scholarship. During this time he worked with Professor Robert Millar and Professor Alan McNeilly at the MRC Human Reproductive Sciences Unit examining the structural determinants of GnRH ligand-receptor interactions.

In 2002, he joined WAIMR as a WAIMR Research Fellow and was awarded a Peter Doherty Fellowship by the National Health & Medical Research Council beginning in 2005. He has won national and international awards in his field and been invited to speak at a number of conferences and universities all over the world.

Qualifications

1998BA (Hons) - Natural Sciences (Pharmacology), Cambridge University (Emmanuel College), UK
2002MA - Natural Sciences (Pharmacology), Cambridge University (Emmanuel College), UK
2003PhD - Molecular Endocrinology, MRC Human Reproductive Sciences Unit & University of Edinburgh, UK
Thesis Title: "Structural determinants of GnRH ligand-receptor interactions"

Research Interests

  • G-protein coupled receptors, including:
    • Gonadotropin-releasing hormone receptor (controlling reproduction).
    • Orexin receptors (controlling wakefulness and metabolism).
    • Thyrotropin-releasing hormone receptors (controlling thyroid function).
  • Interactions between G-protein coupled receptors and arrestins.
  • G-protein coupled receptor dimerization.
  • Bioluminescence resonance energy transfer (BRET).

Research Funding

  • NHMRC Peter Doherty Fellowship
  • NHMRC Project Grant investigating novel strategies to treat drug abuse
  • NHMRC Project Grant to study G-protein coupled receptor mediated-arrestin complexes
  • NHMRC Development Grant to develop resonance energy transfer technologies to detect GPCR heterodimers
  • NHMRC Equipment Grant for a robotic liquid handling workstation
  • NHMRC Equipment Grant for enhanced microscopic imaging
  • ARC Discovery Project Grant to develop a novel technology to assess cellular function
  • Research Contract with Dimerix Bioscience Pty Ltd to study G-protein coupled receptor heterodimers
  • UWA Research Grant investigating novel GPCR interactions with implications for treating alcoholism
  • UWA Research Grant investigating novel protein interactions with the gonadotropin-releasing hormone receptor

Scientific Involvement

  • UK Society for Endocrinology - Member 2000 onwards.
  • US Endocrine Society - Member 2002 onwards.
  • Endocrine Society of Australia - Member 2004 onwards.
  • Australasian Neuroendocrine Group (International Neuroendocrine Federation) - Member 2006 onwards.
  • ARC/NHMRC Research Network on Fluorescence Applications in Biotechnology and Life Sciences (FABLS) - Member 2007 onwards.
  • Australian Society for Medical Research - Member 2008 onwards.
  • Society for Biomolecular Sciences - Member 2008 onwards.

Awards and Honours

2005Inaugural Molecular Pharmacology of G Protein-Coupled Receptors Postdoctoral Poster Prize
2006Endocrine Society of Australia's International Travel Award
2006International Congress of Neuroendocrinology Young Investigator Travel Award
2006Société de Neuroendocrinologie Servier Prize
2007Award for Best Poster Presentation at the British Pharmacological Society Meeting on Cell Signalling
2008Pfizer Global Research and Development Scholarship to present at the GPCR Keystone Symposium
2008Finalist for Western Australian Young Scientist of the Year at the Premier's Science Awards

Top 10 Publications

  1. Pfleger KDG*, Eidne KA. 2006. Illuminating insights into protein-protein interactions using bioluminescence resonance energy transfer (BRET). Nature Methods 3:165-174. [NCBI PubMed Entry] [IF (2008): 13.651]
  2. Pfleger KDG*, Seeber RM, Eidne KA. 2006. Bioluminescence resonance energy transfer (BRET) for the real-time detection of protein-protein interactions. Nature Protocols 1:336-344. [NCBI PubMed Entry] [IF (2008): 4.170]
  3. Pfleger KDG*, Dromey JR, Dalrymple MB, Lim EML, Thomas WG, Eidne KA. 2006. Extended bioluminescence resonance energy transfer (eBRET) for monitoring prolonged protein-protein interactions in live cells. Cellular Signalling 18:1664-1670. [NCBI PubMed Entry] [IF (2008): 4.305]
  4. Pfleger KDG*, Pawson AJ, Millar RP. 2008. Changes to gonadotropin-releasing hormone (GnRH) receptor extracellular loops differentially affect GnRH analog binding and activation: evidence for distinct ligand-stabilized receptor conformations. Endocrinology 149:3118-3129. [NCBI PubMed Entry] [IF (2008): 4.945]
  5. Kocan M, See HB, Sampaio NG, Eidne KA, Feldman BJ, Pfleger KDG*. 2009. Agonist-independent interactions between b-arrestins and mutant vasopressin type II receptors associated with nephrogenic syndrome of inappropriate antidiuresis. Molecular Endocrinology 23:559-571. [NCBI PubMed Entry] [IF (2008): 5.389]
  6. Kocan M, See HB, Seeber RM, Eidne KA, Pfleger KDG*. 2008. Demonstration of improvements to the bioluminescence resonance energy transfer (BRET) technology for the monitoring of G protein-coupled receptors in live cells. Journal of Biomolecular Screening 13:888-898. [NCBI PubMed Entry] [IF (2008): 2.365]
  7. Dalrymple MB, Pfleger KDG*, Eidne KA. 2008. G protein-coupled receptor dimers: Functional consequences, disease states and drug targets. Pharmacology & Therapeutics 118:359-371. [NCBI PubMed Entry] [IF (2008): 9.443]
  8. Pfleger KDG, Bogerd J, Millar RP. 2002. Conformational constraint of mammalian, chicken and salmon GnRHs, but not GnRH II, enhances binding at mammalian and non-mammalian receptors: evidence for pre-configuration of GnRH II. Molecular Endocrinology 16:2155-2162. [NCBI PubMed Entry] [IF (2008): 5.389]
  9. Ferré S, Baler R, Bouvier M, Caron MG, Devi LA, Durroux T, Fuxe K, George SR, Javitch JA, Lohse MJ, Mackie K, Milligan G, Pfleger KDG, Pin JP, Volkow N, Waldhoer M, Woods AS, Franco R. 2009. Building a new conceptual framework for receptor heteromers. Nature Chemical Biology 5:131-134. [NCBI PubMed Entry] [IF (2008): 14.612]
  10. Pfleger KDG*, Eidne KA. 2005. Monitoring the formation of dynamic G-protein-coupled receptor-protein complexes in living cells. Biochemical Journal 385:625-637. [NCBI PubMed Entry] [IF (2008): 4.371]

* Listed as Corresponding Author