Dr Dana Hutchinson
Drug Discovery Biology
Monash Institute of Pharmaceutical Sciences
NHMRC Career Development Fellow
Phone: +61 3 9903 9077
Understanding the role of GPCRs in metabolic disease may pave the way for future therapeutic therapy.
Dr Hutchinson is a NHMRC Career Development Fellow and her research focusses on the metabolic effects elicited by GPCRs and in particular modulation of glucose metabolism by GPCRs. Glucose homeostasis is impaired in type 2 diabetes and identification of non-insulin ways of controlling blood glucose will be important for future therapeutic development. There is increasing recognition that glucose homeostasis can be regulated independently of insulin by activation of GPCRs. Her research has shown that activation of GPCRs in adipocytes and skeletal muscle increases glucose uptake through mechanisms that do not require the same intracellular machinery as that used by insulin. Within this framework, her work has investigated ligand-directed signaling and signaling networks activated by GPCRs. GPCRs are activated not just by classical agonists signaling through one particular G-protein but can couple to multiple downstream effectors and G-proteins in addition to their classically linked G-protein. The pleiotropic actions of GPCRs can occur by a number of different mechanisms including binding to allosteric rather than orthosteric binding sites, presence of scaffolding and signaling partners within a cell, localization of receptors to microdomains within a cell, and the ability of a ligand to bind differentially to particular conformational states of a receptor. She has demonstrated the pleiotropic actions of GPCRs in recombinately expressed cells, with focus now aimed at demonstrating bias in more physiologically relevant cells/tissues.
Selected recent publications
Dehvari N, Hutchinson DS, Nevzorova J, Dallner OS, Sato M, Kocan M, Merlin J, Evans BA, Summers RJ, Bengtsson T. β2-Adrenoceptors increase translocation of GLUT4 via GPCR kinase sites in the receptor C-terminal tail. Br J Pharmacol. 2012;165:1442-56.
Mattsson CL, Csikasz RI, Chernogubova E, Yamamoto DL, Hogberg HT, Amri EZ, Hutchinson DS, Bengtsson T. β₁-Adrenergic receptors increase UCP1 in human MADS brown adipocytes and rescue cold-acclimated β₃-adrenergic receptor-knockout mice via nonshivering thermogenesis. Am J Physiol Endocrinol Metab. 2011;301:E1108-18.
Sato M, Hutchinson DS, Halls ML, Furness SG, Bengtsson T, Evans BA, Summers RJ. Interaction with caveolin-1 modulates G protein coupling of mouse β3-adrenoceptor. J Biol Chem. 2012;287:20674-88.
Evans BA, Broxton N, Merlin J, Sato M, Hutchinson DS, Christopoulos A, Summers RJ. Quantification of functional selectivity at the human α1A-adrenoceptor. Mol Pharmacol. 2011;79:298-307.
Evans BA, Sato M, Sarwar M, Hutchinson DS, Summers RJ. Ligand-directed signalling at β -adrenoceptors. Br J Pharmacol. 2010;159:1022-38.
Merlin J, Evans BA, Csikasz RI, Bengtsson T, Summers RJ, Hutchinson DS. The M3-muscarinic acetylcholine receptor stimulates glucose uptake in L6 skeletal muscle cells by a CaMKK-AMPK-dependent mechanism. Cell Signal. 2010;22:1104-13.