Mark Cleasby
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Mark is a Principal Investigator in the Cardiovascular and Inflammation Biology Group of the Lifestyle research programme. His research interests lie in Endocrinology and Metabolism and specifically in the pathogenesis of insulin resistance in tissues.
Biography
Mark graduated as a Bachelor of Veterinary Medicine and Surgery in 1994 from the University of Edinburgh. Following this he worked as a small animal general veterinary practitioner at various practices until 1998. During this period Mark developed a particular interest in Internal medicine and Endocrinology. In 1998 he returned to the University of Edinburgh to undertake a PhD in the Endocrinology Unit of the Department of Medical Sciences, supervised by Professors Jonathan R. Seckl and Brian R Walker. His PhD, entitled "Mechanisms of insulin resistance in prenatally programmed rats", was awarded in 2002.
From 2002 to 2007 Mark worked as Research Officer and subsequently Senior Research Officer in the Diabetes and Obesity Program of the Garvan Institute, Sydney, Australia. During this period he investigated the molecular and physiological basis of lipid- induced insulin resistance in vivo under the supervision of Professors Edward W. Kraegen and David E. James, and Associate Professor Gregory J. Cooney.
Mark joined the Royal Veterinary College in March 2007 to establish a research group investigating the molecular and physiological basis of insulin resistance, an essential prerequisite for the development of type 2 diabetes.
Research
Mark's resarch has investigated the roles of environmental, genetic and prenatal factors in the development of insulin resistance, predominantly using an in vivo integrative physiology approach. In particular, he has adapted the technique of in vivo electrotransfer for use in the acute interrogation of candidate insulin resistance genes in skeletal muscle, the tissue which is largely responsible for determining whole body insulin-stimulated glucose disposal.
Research Projects
1) Adiponectin action and insulin sensitivity: concerns the mechanisms whereby the adipokine adiponectin influences insulin sensitivity in muscle and liver. Investigation of the roles of putative adiponectin signalling and downstream effector molecules in the effects of adiponectin and their significance for tissue insulin sensitivity using in vivo physiology, cell biological and proteomic approaches. Funded by a Wellcome Trust University Award, previously by a National Health and Medical Research Council of Australia Project Grant and a Diabetes UK Small Grant.
2) Role of inflammation in insulin resistance: investigation of the role of obesity-associated inflammatory cell infiltration into insulin target tissues in mediating local insulin resistance in vitro and in vivo. Funded by an RVC PhD studentship and previously by a Royal Society Research Grant.
3) METAPREDICT- developing predictors of the health benefits of exercise for individuals: Mark is an Investigator on this project, responsible for establishing the mechanisms for differential exercise response in a rodent model. Funded by the European Union FP7.
4) Role of microRNAs in muscle insulin sensitivity: investigation of the potential role of microRNAs in mediating muscle insulin sensitivity and metabolism. Funded by a Diabetes UK PhD studentship.
Collaborators
1) Professor Edward W. Kraegen and colleagues, Garvan Institute of Medical Research, Sydney.
2) Professor Aimin Xu, University of Hong Kong.
3) Professor Jamie Timmons, University of Birmingham.
4) A/Prof Jonathan P. Whitehead, University of Queensland.
5) Dr Pauline Jamieson, Queen's Medical Research Institute, University of Edinburgh.
6) Professor Caroline Wheeler-Jones, Royal Veterinary College, University of London.
Research group members
1) Sejal Patel, BSc PhD, Research assistant (from June 2009).
2) Nicola Talbot, BSc MSc, Postgraduate student (from October 2009).
3) Ditte Andersen, BSc MSc, Postgraduate student (from October 2011).
4) Valentina Gburcik, BSc PhD, Research associate (co-supervised with Prof Jamie Timmons)
5) Charlotte Maile, BVetMed BSc MRCVS, Postgraduate student (co-supervised with Dr Richard Piercy)
6) Helen Woodcock, BSc, Part-time technician.
Teaching
Mark is an academic tutor for 1st and 2nd year BVetMed students and lectures on a BVetMed II Integrated concepts module ("Obesity in Pets") and the BVetMed II Endocrinology module, as well as supervising and marking BSc BioVetSci and summer resaerch projects.
Selected Publications
JAMIESON P. M., CLEASBY M. E., KUPERMAN Y., MORTON N.M., KELLY P.A., BROWNSTEIN D. G., MUSTARD K. J., VAUGHAN J. M., CARTER R. N., HAHN C. N., HARDIE D. G., SECKL J. R., CHEN A. & VALE W. W. (2011) Urocortin 3 transgenic mice exhibit a metabolically favourable phenotype resisting obesity and hyperglycaemia on a high-fat diet. Diabetologia. 2011 Jun 11. [Epub ahead of print]. PubMed ID 21667214
CLEASBY M. E., LAU Q., POLKINGHORNE E., PATEL S. A., LESLIE S. J., TURNER N., COONEY G. J., XU A., KRAEGEN E. W. (2011) The adaptor protein APPL1 increases glycogen accumulation in rat skeletal muscle through activation of the PI3-kinase signalling pathway. J Endocrinol. 210(1):81-92. PubMed ID 21543456
RAMAKRISHNAN S. N., LAU P., CROWTHER L. M., CLEASBY M. E., MILLARD S., LEONG G. M., COONEY G. J. & MUSCAT G. E. (2009) Rev-erb beta regulates the Srebp-1c promoter and mRNA expression in skeletal muscle cells. Biochem Biophys Res Commun. 388, 654-9. PubMed ID 19682428
POLKINGHORNE, E., LAU, Q., COONEY, G. J., KRAEGEN, E. W. & CLEASBY, M. E. (2008) Local activation of the IkappaK-NF-kappaB pathway in muscle does not cause insulin resistance. Am J Physiol Endocrinol Metab 294, E316-325. PubMed ID 18029440
CLEASBY, M. E., REINTEN, T. A., COONEY, G. J., JAMES, D. E. & KRAEGEN, E. W. (2007) Functional studies of Akt isoform specificity in skeletal muscle in vivo; maintained insulin sensitivity despite reduced insulin receptor substrate-1 expression. Mol Endocrinol 21, 215-228. PubMed ID 17021050
BRUCE, C. R., BROLIN, C., TURNER, N., CLEASBY, M. E., VAN DER LEIJ, F. R., COONEY, G. J. & KRAEGEN, E. W. (2007) Overexpression of carnitine palmitoyltransferase I in skeletal muscle in vivo increases fatty acid oxidation and reduces triacylglycerol esterification. Am J Physiol Endocrinol Metab 292, E1231-1237. PubMed ID 17179390
MAXWELL, M. A., CLEASBY, M. E., HARDING, A., STARK, A., COONEY, G. J. & MUSCAT, G. E. (2005) Nur77 regulates lipolysis in skeletal muscle cells. Evidence for cross-talk between the beta-adrenergic and an orphan nuclear hormone receptor pathway. J Biol Chem 280, 12573-12584. PubMed ID 15640143
CLEASBY, M. E., DAVEY, J. R., REINTEN, T. A., GRAHAM, M. W., JAMES, D. E., KRAEGEN, E. W. & COONEY, G. J. (2005) Acute bidirectional manipulation of muscle glucose uptake by in vivo electrotransfer of constructs targeting glucose transporter genes. Diabetes 54, 2702-2711. PubMed ID 16123360
YE, J. M., DZAMKO, N., CLEASBY, M. E., HEGARTY, B. D., FURLER, S. M., COONEY, G. J. & KRAEGEN, E. W. (2004) Direct demonstration of lipid sequestration as a mechanism by which rosiglitazone prevents fatty-acid-induced insulin resistance in the rat: comparison with metformin. Diabetologia 47, 1306-1313. PubMed ID 15232684
CLEASBY, M. E., DZAMKO, N., HEGARTY, B. D., COONEY, G. J., KRAEGEN, E. W. & YE, J. M. (2004) Metformin prevents the development of acute lipid-induced insulin resistance in the rat through altered hepatic signaling mechanisms. Diabetes 53, 3258-3266. PubMed ID 15561958
CLEASBY, M. E., LIVINGSTONE, D. E., NYIRENDA, M. J., SECKL, J. R. & WALKER, B. R. (2003) Is programming of glucocorticoid receptor expression by prenatal dexamethasone in the rat secondary to metabolic derangement in adulthood? Eur J Endocrinol 148, 129-138. PubMed ID 12534366
CLEASBY, M. E., KELLY, P. A., WALKER, B. R. & SECKL, J. R. (2003) Programming of rat muscle and fat metabolism by in utero overexposure to glucocorticoids. Endocrinology 144, 999-1007. PubMed ID 12586777
SECKL, J. R., CLEASBY, M. & NYIRENDA, M. J. (2000) Glucocorticoids, 11beta-hydroxysteroid dehydrogenase, and fetal programming. Kidney Int 57, 1412-1417. PubMed ID 10760076
Outreach Activities
Mark was reponsible for the generation of 30 episodes of the RVC's research podcast, covering a wide variety of clinical and basic research conducted by members of staff at the college.