Prof Mark Sleeman - Researcher Profile

Mark Sleeman

Address

Department of Physiology
Faculty of Medicine, Nursing & Health Sciences, Clayton

Contact Details

Tel: +61 3 990 52516

Email: Mark.Sleeman@monash.edu


Biography

 

Industry experience promotes collaborative approach

Professor Mark Sleeman brings a unique wealth of experience to Monash. Mark arrived in July 2011 after 18 years in the United States, including 13 at the US biotechnology company, Regeneron Pharmaceuticals Inc. As Head of Metabolic Research, Mark oversaw discovery research and therapeutic development for a variety of metabolic diseases. One of his former team’s lead therapeutics is now in Phase-III clinical trials, and Mark says it could be a breakthrough for the treatment of high cholesterol in humans. Having returned to where he did his PhD, and is currently assembling the Physiological Genomics Group to research metabolic disease.

 

 

Mark says his work at Regeneron gave him the opportunity to generate clinically relevant models, do discovery research and quickly make therapeutics to treat associated human diseases. He hopes to bring this approach to his new team.

“The goal is to bring my expertise in the translation of basic science to therapeutic development and put it into the clinic,” Mark says. “We’re starting to initiate some work on the regulation of food intake, body weight, obesity and lipid disorders, but it’s still in very early stages.

“One of the biggest issues facing the pharmaceutical industry and biotechnology is that they don’t have enough validated targets. Academics have a greater understanding of the specific disease mechanisms, but few pathways for development of therapeutics and commercialisation. There is a big disconnect. I hope that we can speed the development process up. 

“I want to bridge that gap and bring technology from the US to Australia. One example would be to integrate the existing monoclonal antibodies facilities at Monash, with new mose models for producing fully human antibodies.  Mark applies two common ideas in his studies. He first aligns his work with clinical groups that are doing relevant research into disease areas of interest, and then uses genetics and genomics to help understand the molecular basis of a disease. One of Mark’s main interests is type 2 diabetes.

“The development of insulin resistance is one of the biggest problems facing type 2 diabetes, and the therapeutic options for combating that problem are limited. We’ve done a lot on the discovery side of things, looking at proteins within the insulin receptor signalling pathways that potentially mediate insulin resistance. We’ve identified intra-cellular proteins that may be targets for therapeutics, but developing therapies and specific molecules to those targets has been very difficult. So it’s still basic research, but it fits nicely with what a lot of other people are doing at Monash,” Mark says.

Mark’s obesity research has also led him to examine non-alcoholic steatohepatitis (NASH), an inflammatory disease of the liver.

“I am very interested in NASH. It ranges from simple fatty liver... to more severe fibrosis and cirrhosis. It’s associated with obesity, as increased adipose mass leads to inappropriate lipid stores in the liver. We’re looking at the inflammation side of this because it appears to be a significant problem. It’s developing as the population becomes more obese.” 

 

Qualifications

DOCTOR OF PHILOSPHY
Institution: Monash University
Year awarded: 1989
BACHELOR OF SCIENCE
Institution: Melbourne Univeristy
Year awarded: 1984

Publications

Journal Articles

Minter, R.R., Cohen, E.S., Wang, B., Liang, M., Vainshtein, I., Rees, G., Eghobamien, L., Harrison, P., Sims, D.A., Matthews, C., Wilkinson, T., Monk, P., Drinkwater, C., Fabri, L., Nash, A., McCourt, M., Jermutus, L., Roskos, L., Anderson, I.K., Sleeman, M.A., 2013, Protein engineering and preclinical development of a GM-CSF receptor antibody for the treatment of rheumatoid arthritis, British Journal of Pharmacology [P], vol 168, issue 1, John Wiley & Sons Ltd, UK, pp. 200-211.

Reichenbach, A., Steyn, F.J., Sleeman, M.W., Andrews, Z.B., 2012, Ghrelin receptor expression and colocalization with anterior pituitary hormones using a GHSR-GFP mouse line, Endocrinology [P], vol 153, issue 11, The Endocrine Society, USA, pp. 5452-5466.

Zhao, T., Liang, G., Li, R.L., Xie, X., Sleeman, M.W., Murphy, A.J., Valenzuela, D., Yancopoulos, G.D., Goldstein, J.L., Brown, M.S., 2011, Ghrelin O-acyltransferase (GOAT) is essential for growth hormone-mediated survival of calorie-restricted mice, Proceedings Of The National Academy Of Sciences Of The United States Of America [P], vol 107, issue 16, National Academy of Sciences, USA, pp. 7467-7472.

Kang, K., Schmahl, J., Lee, J., Garcia, K., Patil, K., Chen, A., Keene, M., Murphy, A., Sleeman, M.W., 2011, Mouse ghrelin-O-acyltransferase (GOAT) plays a critical role in bile acid reabsorption, Faseb Journal [P], vol 26, issue 1, Federation of American Societies for Experimental Biology, USA, pp. 259-271.

Kang, K., Zmuda, E., Sleeman, M.W., 2011, Physiological role of ghrelin as revealed by the ghrelin and GOAT knockout mice, Peptides [P], vol 32, issue 11, Elsevier Inc, USA, pp. 2236-2241.

Abizaid, A., Mineur, Y.S., Roth, R.H., Elsworth, J.D., Sleeman, M.W., Picciotto, M.R., Horvath, T.L., 2011, Reduced locomotor responses to cocaine in ghrelin-deficient mice, Neuroscience [P], vol 192, Pergamon, UK, pp. 500-506.

Perez-Tilve, D., Hofmann, S.M., Basford, J., Nogueiras, R., Pfluger, P.T., Patterson, J.T., Grant, E., Wilson-Perez, H.E., Granholm, N.A., Arnold, M., Trevaskis, J.L., Butler, A.A., Davidson, W.S., Woods, S.C., Benoit, S.C., Sleeman, M.W., DiMarchi, R.D., Hui, D.Y., Tschop, M.H., 2010, Melanocortin signaling in the CNS directly regulates circulating cholesterol, Nature Neuroscience [P], vol 13, issue 7, Nature Publishing Group, USA, pp. 877-882.

Watson, E., Fargali, S., Okamoto, H., Sadahiro, M., Gordon, R.E., Chakraborty, T., Sleeman, M.W., Salton, S.R., 2009, Analysis of knockout mice suggests a role for VGF in the control of fat storage and energy expenditure, BMC Physiology [P], vol 9, BioMed Central Ltd, UK, pp. 1-20.

Blum, I.D., Patterson, Z., Khazall, R., Lamont, E.W., Sleeman, M.W., Horvath, T.L., Abizaid, A., 2009, Reduced anticipatory locomotor responses to scheduled meals in ghrelin receptor deficient mice, Neuroscience [P], vol 164, issue 2, Pergamon, UK, pp. 351-359.

Nogueiras, R., Lopez, M., Lage, R., Perez-Tilve, D., Pfluger, P.T., Mendieta-Zeron, H., Sakkou, M., Wiedmer, P., Benoit, S.C., Datta, R., Dong, J.Z., Culler, M.D., Sleeman, M.W., Vidal-Puig, A., Horvath, T.L., Treier, M., Dieguez, C., Tschop, M.H., 2008, Bsx, a novel hypothalamic factor linking feeding with locomotor activity, is regulated by energy availability, Endocrinology [P], vol 149, issue 6, The Endocrine Society, USA, pp. 3009-3015.

Wang, Q., Elghazi, L., Martin, S., Martins, I., Srinivasan, R.S., Geng, X., Sleeman, M.W., Collombat, P., Houghton, J., Sosa-Pineda, B., 2008, Ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenum, Developmental Dynamics [P], vol 237, issue 1, John Wiley & Sons Inc, USA, pp. 51-61.

Lopez, M., Lage, R., Saha, A.K., Perez-Tilve, D., Vazquez, M., Varela, L., Sangiao-Alvarellos, S., Tovar, S., Raghay, K., Rodriguez-Cuenca, S., Deoliveira, R.M., Castaneda, T.R., Datta, R., Dong, J.Z., Culler, M.D., Sleeman, M.W., Alvarez, C.V., Gallego, R., Lelliott, C.J., Carling, D., Tschop, M.H., Dieguez, C., Vidal-Puig, A., 2008, Hypothalamic fatty acid metabolism mediates the orexigenic action of ghrelin, Cell Metabolism [P], vol 7, issue 5, Cell Press, USA, pp. 389-399.

Fegley, D.B., Holmes, A., Riordan, T., Faber, C.A., Weiss, J.R., Ma, S., Batkai, S., Pacher, P., Dobolyl, A., Murphy, A., Sleeman, M.W., Usdin, T.B., 2008, Increased fear- and stress-related anxiety-like behavior in mice lacking tuberoinfundibular peptide of 39 residues, Genes Brain And Behavior [P], vol 7, issue 8, Wiley-Blackwell Publishing Inc, USA, pp. 933-942.

Pfluger, P.T., Kirchner, H., Gunnel, S., Schrott, B., Perez-Tilve, D., Fu, S., Benoit, S.C., Horvath, T.L., Joost, H., Wortley, K.E., Sleeman, M.W., Tschop, M.H., 2008, Simultaneous deletion of ghrelin and its receptor increases motor activity and energy expenditure, American Journal Of Physiology-Gastrointestinal And Liver Physiology [P], vol 294, issue 3, American Physiological Society, USA, pp. G610-G618.

Sleeman, M., Latres, E., 2008, The CAMplexities of central ghrelin, Cell Metabolism [P], vol 7, issue 5, Cell Press, USA, pp. 361-362.

Raz, R., Stricker, S., Gazzerro, E., Clor, J.L., Witte, F., Nistala, H., Zabski, S., Pereira, R.C., Stadmeyer, L., Wang, X., Gowen, L., Sleeman, M.W., Yancopoulos, G.D., Canalis, E., Mundlos, S., Valenzuela, D.M., Economides, A.N., 2008, The mutation ROR2W749X, linked to human BDB, is a recessive mutation in the mouse, causing brachydactyly, mediating patterning of joints and modeling recessive Robinow syndrome, Development [P], vol 135, issue 9, The Company of Biologists Ltd, UK, pp. 1713-1723.

Munzberg, H., Jobst, E., Bates, S., Jones, J., Villanueva, E., Leshan, R., Bjornholm, M., Elmquist, J., Sleeman, M., Cowley, M.A., Myers Jr., M., 2007, Appropriate inhibition of orexigenic hypothalamic arcuate nucleus neurons independently of leptin receptor/STAT3 signaling, Journal of Neuroscience, vol 27, issue 1, Society for Neuroscience, USA, pp. 69-74.

Faber, C.A., Dobolyi, A., Sleeman, M.W., Usdin, T.B., 2007, Distribution of tuberoinfundibular peptide of 39 residues and its receptor, parathyroid hormone 2 receptor, in the mouse brain, Journal of Comparative Neurology [P], vol 502, issue 4, John Wiley & Sons Inc, USA, pp. 563-583.

Okamoto, H., Latres, E., Liu, R., Thabet, K., Murphy, A., Valenzeula, D., Yancopoulos, G.D., Stitt, T., Glass, D.J., Sleeman, M.W., 2007, Genetic deletion of Trb3, the mammalian Drosophila tribbles homolog, displays normal hepatic insulin signaling and glucose homeostasis, Diabetes [P], vol 56, issue 5, American Diabetes Association, USA, pp. 1350-1356.

Torres, R., Croll, S.D., Vercollone, J., Reinhardt, J., Griffiths, J., Zabski, S., Anderson, K.D., Adams, N.C., Gowen, L., Sleeman, M.W., Valenzuela, D., Wiegand, S.J., Yancopoulos, G.D., Murphy, A.J., 2007, Mice genetically deficient in neuromedin U receptor 2, but not neuromedin U receptor 1, have impaired nociceptive responses, Pain [P], vol 130, issue 3, Elsevier BV, The Netherlands, pp. 267-278.

Wortley, K.E., Garcia, K., Okamoto, H., Thabet, K., Anderson, K.D., Shen, V., Herman, J.P., Valenzuela, D., Yancopoulos, G.D., Tschop, M.H., Murphy, A.J., Sleeman, M.W., 2007, Peptide YY regulates bone turnover in rodents, Gastroenterology [P], vol 133, issue 5, W.B. Saunders Co, USA, pp. 1534-1543.

Xu, J., Gowen, L., Raphalides, C., Hoyer, K.K., Weinger, J.G., Renard, M., Troke, J.J., Vaitheesyaran, B., Lee, W.P., Saad, M.F., Sleeman, M.A., Teitell, M.A., Kurland, I.J., 2006, Decreased hepatic futile cycling compensates for increased glucose disposal in the Pten heterodeficient mouse, Diabetes [P], vol 55, issue 12, American Diabetes Association, USA, pp. 3372-3380.

Diano, S., Farr, S.A., Benoit, S.C., McNay, E.C., da Silva, I., Horvath, B., Gaskin, F.S., Nonaka, N., Jaeger, L.B., Banks, W.A., Morley, J.E., Pinto, S., Sherwin, R.S., Xu, L., Yamada, K.A., Sleeman, M., Tschop, M.H., Horvath, T.L., 2006, Ghrelin controls hippocampal spine synapse density and memory performance, Nature Neuroscience [P], vol 9, issue 3, Nature Publishing Group, USA, pp. 381-388.

Abizaid, A., Liu, Z., Andrews, Z.B., Shanabrough, M., Borok, E., Elsworth, J.D., Roth, R.H., Sleeman, M.W., Picciotto, M.R., Tschop, M.H., Gao, X., Horvath, T.L., 2006, Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite, Journal of Clinical Investigation, vol 116, issue 12, American Society for Clinical Investigation, USA, pp. 3229-3239.

Grants

Title:
Seahorse XF24 Extracellular Flux Analyser.
Investigators:
Watt, M, Mitchell, C, Tiganis, T, Currie, P, Andrews, Z, Clarke, I, O'Bryan, M, Cowley, M, Sleeman, M, Dowling, D, Gabriel, K, Risbridger, G, Bruce, C, Brown, K, Johns, T, Sobey, C, Henry, B
Funding:
(2012 - 2016). National Health & Medical Research Council (NHMRC).
Title:
The Hologic 'A' Bone Densitometry System.
Investigators:
Cowley, M, Sleeman, M, Spanswick, D
Funding:
(2012 - 2016). National Health & Medical Research Council (NHMRC).
Title:
Melbourne and Monash integrated Proteomics Facility.
Investigators:
Nice, E, Bacic, A, Williamson, N, O'Hair, R, Wilce, J, Mackay, C, Bateman, J, Sleeman, M, McCluskey, J, Villadangos, J
Funding:
(2012 - 2016). Australian Research Council (ARC).
(2013 - 2017). Monash University.