<b>Professor Mike Waters</b><br>
Group Leader, Cell Biology and Molecular Medicine Division<br><p>
P: +61 7 3346 2037<br>
E: m.waters@imb.uq.edu.au<p>
<b>Keywords</b><br>
- obesity<br>
- cancer<br>
- liver failure<br>
- dementia<br>
- short stature<br>
- giantism<br>
- stem cell biology
Professor Mike Waters
Group Leader, Cell Biology and Molecular Medicine Division

P: +61 7 3346 2037
E: m.waters@imb.uq.edu.au

Keywords
- obesity
- cancer
- liver failure
- dementia
- short stature
- giantism
- stem cell biology

Role of growth hormone in human development

Growth hormone affects all of us throughout our lives. In childhood and adolescence, it causes us to grow and determines our final height. In adulthood, it regulates body composition—increasing muscle, strengthening bone and decreasing fat. Both in childhood and adolescence, it is increased during exercise, improving our cognitive ability. In old age, at least in rodents, it regulates our lifespan. Our research uses a variety of approaches to study the molecular means used by growth hormone to achieve these changes.

The growth hormone receptor determines the degree of cellular response to growth hormone. Through sophisticated techniques, we have developed a detailed molecular understanding of how the growth hormone receptor is activated by the cell, the first such model for the 30 receptors in this cytokine receptor class. As the first fruit from this landmark discovery, we have created growth hormone receptors that are permanently activated. These are being used to promote hormone-free growth of fish in Chinese aquaculture, with the potential to be applied to other aquaculture species such as lobster.

We also recently described a growth hormone receptor-initiated signalling pathway that is essential for expression of a powerful immune tolerance molecule that we predict will improve the success of human liver and kidney transplants. We are currently trialling this molecule in animal models of liver regeneration. We have also demonstrated the use of growth hormone therapy as a treatment for hepatic steatosis (fatty liver) in animal models, and determined how this works.

We have found that growth hormone acts in normally fed mice to burn fat, so as to maintain a normal amount of fat. We find it does this by inducing a special type of fat-burning cell known as the beige cell. This changes the view of fat as a simple storage organ that supplies lipid for muscle to burn, to a view where the fat regulates its own level both by controlling appetite and by burning itself.

Finally, the striking resistance of growth hormone-deficient and growth hormone-receptor mutant mice, and humans with defective growth hormone receptors to cancer has led us to elucidate the pathways involved, and to seek to develop small molecule (drug) growth hormone antagonists of therapeutic value in cancer treatment. We have evidence that the erroneous synthesis of growth hormone within cells can promote cancers, and have identified a variant growth hormone receptor that promotes lung cancer by inhibiting receptor degradation. However, growth hormone acting externally is prevented from doing this by a set of opposing factors, which means it is a safe therapeutic.

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Research in the news

16 May 2014: Eureka moment for 45-year Australian study (AAP)

Research training opportunitiesWaters Lab

Please see IMB's postgraduate website for more information.

Key publications

View more publications by Professor Waters via Pubmed or via UQ Researchers.

Andrew J. Brooks, Wei Dai, Megan L. O’Mara, Daniel Abankwa, Yash Chhabra, Rebecca A. Pelekanos, Olivier Gardon, Kathryn A. Tunny, Kristopher M. Blucher, Craig J. Morton, Michael W. Parker, Emma Sierecki, Yann Gambin, Guillermo A. Gomez, Kirill Alexandrov, Ian A. Wilson, Manolis Doxastakis, Alan E. Mark, and Michael J. Waters. (2014). Mechanism of Activation of Protein Kinase JAK2 by the Growth Hormone Receptor. Science 344, 1249783. [ACCESS THE FULL TEXT VIA SCIENCE: http://www.sciencemag.org/content/344/6185/1249783.full?ijkey=1yEhidxEhJvIM&keytype=ref&siteid=sci]

Blackmore, D.G., Gomohammadi, M.G., Large, B., Waters, M.J., and Rietze, R.L. (2009). Exercise increases neural stem cell number in a growth hormone-dependent manner, augmenting the regenerative response in aged mice. Stem Cells 27: 2044-2052.

Conway-Campbell, B.L., Brooks, A.J., Robinson, P.J., Perani, M., and Waters, M.J. (2008). The extracellular domain of the growth hormone receptor interacts with coactivator activator to promote cell proliferation. Molecular Endocrinology 22: 2190-2202.

Lichanska, A.M., and Waters, M.J. (2008). How growth hormone controls growth, obesity and sexual dimorphism. Trends in Genetics 24: 41-47.

Rowlinson, S.W., Yoshizato, H., Barclay, J.L., Brooks, A.J., Behncken, S.N., Kerr, L.M., Millard, K., Palethorpe, K., Nielsen, K., Clyde-Smith, J., Hancock, J.F., and Waters, M.J. (2008). An agonist-induced conformational change in the growth hormone receptor determines the choice of signalling pathway. Nature Cell Biology 10: 740-747.

Barclay JL, Nelson CN, Ishikawa M, Murray LA, Kerr LM, McPhee TR, Powell EE, Waters MJ. (2011) GH-dependent STAT5 signaling plays an important role in hepatic lipid metabolism. Endocrinology. 152(1):181-92. 

Group contacts

Dr Andrew Brooks
Research staff
+61 7 334 62362
+61 7 334 62720
a.brooks@imb.uq.edu.au
Mr Yash Chhabra
Research higher degree student
+61 7 334 62362
s4152875@student.uq.edu.au
Dr Caroline Nelson
Research staff
+61 7 334 62362
+61 7 334 62720
caroline.nelson@imb.uq.edu.au
Mrs Tania Brooks
Research staff
+61 7 334 62362
+61 7 334 62366
t.brooks@imb.uq.edu.au
Ms Makerita Ieremia
Research higher degree student
+617 334 62362
makerita.ieremia@uqconnect.edu.au
Professor Mike Waters
Group Leader
+61 7 334 62037
m.waters@imb.uq.edu.au