Ms Dana Hutchinson - Researcher Profile

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Address

Faculty of Pharmacy and Pharmaceutical Sciences
381 Royal Parade, Parkville

Biography

 

The complexities of cell communication

There is far more going on at the surface of the body's cells than had previously been imagined. Dr Dana Hutchinson's research could turn this newly discovered complexity into better treatments for patients.

 

 

Dana had a head start in understanding the complex world of pharmaceutical science. The daughter of a pharmacologist, she has been familiar with the fundamentals of the mechanisms that drive the human body on a cellular level from a young age.

Now her own research is helping explain the newly discovered intricacies occurring at the cell surfaces deep within all of us.

Dana studies the way chemical interactions are regulated by receptors on the cell surface. 

The largest and most diverse family of receptors are G-protein coupled receptors (GPCRs), which relay information from external stimuli to cells. GPCRs are the focus of almost a third of all current therapeutics, making them particularly attractive to pharmaceutical companies.

Dana is investigating how GPCRs can modulate glucose metabolism in skeletal muscle and fat, research that could have major implications for the treatment of diabetes.

It is hoped that GPCRs prove to be more effective at targeting and interacting with the key protein, AMP-activated kinase (AMPK), which plays a pivotal role in balancing the body's energy by regulating glucose metabolism, food intake and body weight. By targeting the protein only in the desired tissues, you could reduce potential side effects and increase the positive effects of treatment.

"You can get specificity with GPCRs that you don't otherwise because they are differentially expressed throughout the whole body," Dana says.

"AMPK as a target itself is expressed in most cells - obviously at higher degrees in ones that are important for metabolism like the heart, pancreas and skeletal muscle – so if you want to activate AMPK in skeletal muscle to increase glucose uptake, you could actually get reactions in the brain telling you to eat more, which is not a good thing. 

"So if you could get a GPCR that maybe isn't expressed in the brain but is just in skeletal muscle you can get specificity that way." 

Dana's GPCR work has been supported with a National Health and Medical Research Council Career Development Awards Scheme grant, which she received in 2009.

This work is complemented by a study of the relatively new field of ligand-directed stimulus bias, which attempts to discover why some drugs activate different cell signal pathways despite having the same characteristics.

The most common example of this kind of irregularity is found in the beta blocker class of drugs often used to regulate heart problems in older Australians. 

"All beta blockers were designed the same way originally, so they stop the action of noradrenaline and adrenaline on your heart, so your heart rate will go down," Dana says.

"But what they are seeing clinically is that some beta blockers are better than others, having a more cardio-protective effect when theoretically the drugs should all be the same.

"So they're actually activating the receptor in a different way and causing beneficial effects in themselves. We are trying to understand why this difference is occurring, and working to maybe select drugs to activate the pathways that give the cardio-protective effect."

Understanding this process could lead to creating more selective drugs that offer better treatments to patients.

 

Qualifications

PHD
Institution: Monash University
Year awarded: 2002
B.SC. (HONS.)
Institution: University of Melbourne
Year awarded: 1998

Publications

Journal Articles

Sato, M., Hutchinson, D.S., Halls, M.L., Furness, S.G.B., Bengtsson, T., Evans, B.A., Summers, R.J., 2012, Interaction with caveolin-1 modulates G protein coupling of the mouse beta3-adrenoceptor, Journal Of Biological Chemistry [P], vol 287, issue 24, American Society for Biochemistry and Molecular Biology Inc., USA, pp. 20674-20688.

Gibbs, M.E., Hutchinson, D.S., 2012, Rapid turnover of glycogen in memory formation, Neurochemical Research [P], vol 37, issue 11, Springer New York LLC, USA, pp. 2456-2463.

Dehvari, N., Hutchinson, D., Nevzorova, J., Dallner, O., Sato, M., Kocan, M., Merlin, J., Evans, B., Summers, R., Bengtsson, T., 2011, Beta(2)-adrenoceptors increase translocation of GLUT4 via GPCR kinase sites in the receptor C-terminal tail, British Journal of Pharmacology [P], vol 165, issue 5, John Wiley & Sons Ltd, UK, pp. 1442-1456.

Evans, B.A., Broxton, N., Merlin, J., Sato, M., Hutchinson, D.S., Christopoulos, A., Summers, R.J., 2011, Quantification of functional selectivity at the human {alpha}1A-adrenoceptor, Molecular Pharmacology [P], vol 79, issue 2, American Society for Pharmacology & Experimental Therapeutics, USA, pp. 298-307.

Catus, S.L., Gibbs, M.E., Sato, M., Summers, R.J., Hutchinson, D.S., 2011, Role of beta-adrenoceptors in glucose uptake in astrocytes using beta-adrenoceptor knockout mice, British Journal of Pharmacology [P], vol 162, issue 8, John Wiley & Sons Ltd, UK, pp. 1700-1715.

Oberg, A., Yassin, K., Csikasz, R., Dehvari, N., Shabalina, I., Hutchinson, D., Wilcke, M., Goran-Ostenson, C., Bengtsson, T., 2011, Shikonin increases glucose uptake in skeletal muscle cells and improves plasma glucose levels in diabetic goto-kakizaki rats, PLoS ONE [P], vol 6, issue 7, Public Library of Science, USA, pp. e22510-1-e22510-10.

Hutchinson, D.S., Catus, S.L., Merlin, J., Summers, R.J., Gibbs, M.E., 2011, alpha{2}-Adrenoceptors activate noradrenaline-mediated glycogen turnover in chick astrocytes, Journal Of Neurochemistry [P], vol 117, issue 5, Wiley-Blackwell Publishing Ltd, UK, USA, pp. 915-926.

Evans, B., Sato, M., Sarwar, M., Hutchinson, D., Summers, R., 2010, Ligand-directed signalling at beta-adrenoceptors, British Journal of Pharmacology [P], vol 159, issue 5, John Wiley & Sons Ltd., United Kingdom, pp. 1022-1038.

Gibbs, M.E., Hutchinson, D.S., Summers, R.J., 2010, Noradrenaline release in the locus coeruleus modulates memory formation and consolidation; roles for alpha- and beta-adrenergic receptors, Neuroscience [P], vol 170, issue 4, Pergamon, UK, France, pp. 1209-1222.

Merlin, J., Evans, B.A., Csikasz, R.I., Bengtsson, T., Summers, R.J., Hutchinson, D.S., 2010, The M3-muscarinic acetylcholine receptor stimulates glucose uptake in L6 skeletal muscle cells by a CaMKK-AMPK-dependent mechanism, Cellular Signalling [P], vol 22, issue 7, Elsevier Inc., USA, pp. 1104-1113.

Gibbs, M.E., Rodricks, C.L., Hutchinson, D.S., Summers, R.J., Miller, S.L., 2009, Importance of adrenergic receptors in prenatally induced cognitive impairment in the domestic chick, International Journal of Developmental Neuroscience, vol 27, Pergamon, UK, pp. 27-35.

Gibbs, M.E., Hutchinson, D.S., Hertz, L., 2008, Astrocytic involvement in learning and memory consolidation, Neuroscience & Biobehavioral Reviews, vol 32, issue 5, Pergamon, United Kingdom, pp. 927-944.

Hutchinson, D.S., Summers, R.J., Gibbs, M.E., 2008, Energy metabolism and memory processing: Role of glucose transport and glycogen in responses to adrenoceptor activation in the chicken, Brain Research Bulletin, vol 76, issue 3, Elsevier Inc., United States, pp. 224-234.

Gibbs, M.E., Bowser, D.N., Hutchinson, D.S., Loiacono, R., Summers, R.J., 2008, Memory processing in the avian hippocampus involves interactions between beta-adrenoceptors, glutamate receptors, and metabolism, Neuropsychopharmacology, vol 33, issue 12, Nature Publishing Group, United Kingdom, pp. 2831-2846.

Hutchinson, D.S., Summers, R.J., Bengtsson, T., 2008, Regulation of AMP-activated protein kinase activity by G-protein coupled receptors: Potential utility in treatment of diabetes and heart disease, Pharmacology & Therapeutics, vol 119, issue 3, Elsevier Inc., United States, pp. 291-310.

Gibbs, M.E., Hutchinson, D.S., Summers, R.J., 2008, Role of beta-Adrenoceptors in Memory Consolidation: beta3-Adrenoceptors Act on Glucose Uptake and beta2-Adrenoceptors on Glycogenolysis, Neuropsychopharmacology, vol 33, Nature Publishing Group, London England UK, pp. 2384-2397.

Sato, M., Hutchinson, D.S., Evans, B.A., Summers, R.J., 2008, The beta3-adrenoceptor agonist 4-[[(hexylamino)carbonyl]amino]-N-[4-[2-[[(2S)-2-hydroxy-3-(4-hydroxyphenoxy)propyl]amino]ethyl]-phenyl]-benzenesulfonamide (L755507) and antagonist [...], Molecular Pharmacology, vol 74, issue 5, American Society for Pharmacology and Experimental Therapeutics, United States, pp. 1417-1428.

Sato, M., Hutchinson, D.S., Evans, B.A., Summers, R.J., 2007, Functional domains of the mouse beta3-adrenoceptor associated with differential G-protein coupling, Biochemical Society Transactions, vol 35, issue Pt 5, Portland Press Ltd, London, England, UK, pp. 1035-1037.

Yamamoto, D.L., Hutchinson, D.S., Bengtsson, T., 2007, 2-adrenergic activation increases glycogen synthesis in L6 skeletal muscle cells through a signalling pathway independent of cyclic AMP, Diabetologia, vol 50, issue 1, Springer, New York, NY, USA, pp. 158-167.

Scheele, C., Nielsen, A.R., Walden, T.B., Sewell, D.A., Fischer, C.P., Brogan, R.J., Petrovic, N., Larsson, O., Tesch, P.A., Wennmalm, K., Hutchinson, D.S., Cannon, B., Wahlestedt, C., Pedersen, B., Timmons, J.A., 2007, Altered regulation of the PINK1 locus: a link between type 2 diabetes and neurodegeneration?, FASEB Journal, vol 21, issue 13, Federation of American Society of Experimental Biologists, Bethesda MD USA, pp. 3653-3665.

Hutchinson, D.S., Csikasz, R.I., Yamamoto, D.L., Shabalina, I.G., Wikstrom, P., Wilcke, M., Bengtsson, T., 2007, Diphenylene iodonium stimulates glucose uptake in skeletal muscle cells through mitochondrial complex I inhibition and activation of AMP-activated protein kinase, Cellular Signalling, vol 19, issue 7, Elsevier Science Inc, New York NY USA, pp. 1610-1620.

Sato, M., Horinouchi, T., Hutchinson, D.S., Evans, B.A., Summers, R.J., 2007, Ligand-directed signaling at the beta3-adrenoceptor produced by 3-(2-ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol oxalate (SR59230A) relative to receptor agonists, Molecular Pharmacology, vol 72, issue 5, American Society of Pharmacology & Experimental Therapeutics, Bethesda MD USA, pp. 1359-1368.

Hutchinson, D.S., Summers, R.J., Gibbs, M.E., 2007, beta2- and beta3-Adrenoceptors activate glucose uptake in chick astrocytes by distinct mechanisms: A mechanism for memory enhancement?, Journal of Neurochemistry, vol 103, issue 3, Blackwell Publishing, Oxford England UK, pp. 997-1008.

Yamamoto, D.L., Hutchinson, D.S., Bengtsson, T., 2006, 2-adrenergic activation increases glycogen synthesis in L6 skeletal muscle cells through a signalling pathway independent of cyclic AMP, Diabetologia, vol 50, issue 1, Springer, New York NY USA, pp. 158-167.

Hutchinson, D.S., Bengtsson, T., 2006, AMP-activated protein kinase activation by adrenoceptors in L6 skeletal muscle cells: Mediation by alpha1-adrenoceptors causing glucose uptake, Diabetes, vol 55, American Diabetes Association, Alexandria USA, pp. 682-690.

Hutchinson, D.S., Chernogubova, E., Sato, M., Summers, R.J., Bengtsson, T., 2006, Agonist effects of zinterol at the mouse and human beta3-adrenoceptor, Naunyn-Schmiedeberg's Archives of Pharmacology, vol 373, issue 2, Springer, Berlin Germany, pp. 158-168.

Chernogubova, E., Hutchinson, D.S., Nedergaard, J., Bengtsson, T., 2005, Alpha1- and beta1-adrenoceptor signaling fully compensates for beta3-adrenoceptor deficiency in brown adipocyte norepinephrine-stimulated glucose uptake, Endocrinology, vol 146, issue 5, The Endocrine Society, Chevy Chase MD USA, pp. 2271-2284.

Hutchinson, D.S., Bengtsson, T., 2005, Alpha1A-adrenoceptors activate glucose uptake in L6 muscle cells through a phospholipase C-, phosphatidylinositol-3 kinase-, and atypical protein kinase C-dependent pathway, Endocrinology, vol 146, issue 2, Endocrine Soc, Chevy Chase USA, pp. 901-912.

Hutchinson, D.S., Sato, M., Evans, B.A., Christopoulos, A., Summers, R.J., 2005, Evidence for pleiotropic signaling at the mouse beta3-adrenoceptor revealed by SR59230A [3-(2-ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol oxalate], The Journal of Pharmacology and Experimental Therapeutics, vol 312, issue 3, American Society for Pharmacology and Experimental Therapeutics, Bethesda USA, pp. 1064-1074.

Sato, M., Hutchinson, D.S., Bengtsson, T., Floren, A., Langel, U., Horinouchi, T., Evans, B.A., Summers, R.J., 2005, Functional domains of the mouse beta3-adrenoceptor associated with differential G-protein coupling, The Journal of Pharmacology and Experimental Therapeutics, vol 315, issue 3, American Society for Pharmacology and Experimental Therapeutics, USA, pp. 1354-1361.

Hutchinson, D.S., Chernogubova, E., Dallner, O.S., Cannon, B., Bengtsson, T., 2005, beta-Adrenoceptors, but not alpha-adrenoceptors, stimulate AMP-activated protein kinase in brown adipocytes independently of uncoupling protein-1, Diabetologia, vol 48, Springer, New York USA, pp. 2386-2395.

Popp, B.D., Hutchinson, D.S., Evans, B.A., Summers, R.J., 2004, Stereoselectivity for interactions of agonists and antagonists at mouse, rat and human 3-adrenoceptors, European Journal of Pharmacology, vol 484, issue 2-3, Elsevier, Amsterdam The Netherlands, pp. 323-331.

Summers, R.J., Broxton, N., Hutchinson, D.S., Evans, B.A., 2004, The Janus faces of adrenoceptors: factors controlling the coupling of adrenoceptors to multiple signal transduction pathways, Clinical and Experimental Pharmacology and Physiology, vol 31, issue 11, Blackwell Publishing, Carlton Vic Australia, pp. 822-827.

Hutchinson, D.S., Bengtsson, T., Evans, B.A., Summers, R.J., 2002, Mouse 3a- and 3b- adrenoceptors expressed in Chinese hamster ovary cells display identical pharmacology but utilize distinct signalling pathways, British Journal of Pharmacology, vol 135, Nature Publishing Group, London England, pp. 1903-1914.

Hutchinson, D.S., Evans, B.A., Summers, R.J., 2001, b1-Adrenoceptors compensate for b3-adrenoceptors in ileum from b3-adrenoceptor knock-out mice, British Journal of Pharmacology, vol 132, issue 2, Nature Publishing Group, Basingstoke England, pp. 433-442.

Hutchinson, D.S., Evans, B.A., Summers, R.J., 2000, Beta3-adrenoceptor regulation and relaxation responses in mouse ileum, British Journal of Pharmacology, vol 129, Stockton Press, Basingstoke England, pp. 1251-1259.

Conference Proceedings

Hutchinson, D.S., Cannon, B., 2006, Adrenoceptor mediated phosphorylation of AMPK differs between brown adipose tissue and skeletal muscle, Acta Pharmacologica Sinica, 2-7/07/2006, Blackwell Publishing, Oxford England, p. 1276.

Sato, M., Horinouchi, T., Hutchinson, D.S., Evans, B.A., 2006, Multiple signalling pathways of the mouse beta(3)-adrenoceptor stably expressed in CHO-K1 cells, Acta Pharmacologica Sinica, 2-7/7/2006, Blackwell Publishing, Oxford London UK, p. 410.

Horinouchi, T., Sato, M., Hutchinson, D.S., Evans, B.A., Summers, R.J., 2006, The role of the C-terminal domain in mouse beta(3)-adrenoceptor signalling, Journal of Pharmacological Sciences, 26-30/6/2006, Japanese Pharmacogical Society, Kyoto Japan, p. 126.

Hutchinson, D.S., Summers, R.J., 1999, Characterization of ileal beta-adrenoceptor mediated responses in beta3-adrenoceptor knockout mice, Proceedings of the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, Sydney, NSW,. Dec 1999, ASCEPT, Sydney NSW Australia, pp. 104-Post 1-64.

Summers, R.J., Hutchinson, D.S., Evans, B.A., 1998, B3 -adrenorecoptors: differential regulations and novel subtypes, Pharmacology and Toxicology, Nordic Pharmacological Society, Copenhagan Denmark, pp. 37-39.

Evans, B.A., Hutchinson, D.S., Papaioannou, M., Hamilton, S., Summers, R.J., 1998, Cloing and expression of two isoforms of the b3 -adrenoceptor which are differentially expressed in mouse tissues, Proceedings of the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, Hobart, TAS, December 1998, ASCEPT, Sydney NSW Australia, p. 130.

Hutchinson, D.S., Evans, B.A., Summers, R.J., 1998, Differential regulation of b3-adrenoceptors (ARs) in mouse ileum and adipose tissues by the b3-AR agonist CL 316243 and the b3-AR antagonist SR 59230A, Naunyn-Schmiedeberg's Archives of Pharmacology, Munchen, Germany, July 1998, Springer, Berlin, p. R613.

Hutchinson, D.S., Evans, B.A., Summers, R.J., 1998, The pharmacological properties of the mouse b3a and b3b - adrenoceptor expressed in CHO - KI cells studied using the cytosensor R microphysiometer, Proceedings of the Australasian Society of Clinical and Experimental Pharmacologists and Toxicologists, Hobart, TAS, December 1998, ASCEPT, Sydney NSW Australia, p. 174.

Postgraduate Research Supervisions

Current Supervision

Program of Study:
(DOCTORATE BY RESEARCH).
Thesis Title:
Novel GPCR targets for the treatment of type 2 diabetes and metabolic disease.
Supervisors:
Summers, R (Main), Hutchinson, D (Associate).