David Kennaway Associate Professor / Principal Research Fellow BSc (Hons), PhD (Adelaide) Email: david.kennaway@adelaide.edu.au Contact information Duties: Full time Research Only Academic, Postgraduate Coordinator.

Research interests

My research program is aimed at gaining an understanding of biological rhythms and how they are related to our well being. It has been known for many years that a wide range of physiological systems exhibit daily rhythms, for example, hormone secretion, body temperature and sleep/activity. The major site of rhythm generation and entrainment to the environment is the suprachiasmatic nucleus (SCN) in the hypothalamus. The discovery of the suite of clock gene transcription factors and the recognition that they are rhythmically expressed in a wide range of tissues and organs has led to a broadening of research on the potential roles of circadian rhythms in health and disease.

The Circadian Physiology Group is actively working in several areas ranging from the control of SCN function to the consequences of rhythm disruption on systems.

1. The role of clock genes in the maintenance of metabolic homeostasis. It has been found that the genes for many key proteins involved in cellular metabolism are rhythmically expressed through direct influences of the clock genes, Clock and Bmal1. We are utilising Bmal1 knockout mice as well as our unique melatonin proficient Clock+MEL mutant mice in studies on glucose metabolism and insulin function. In addition we have established a rapid phase shift model that allows us to investigate the impact of simulated shiftwork on metabolic homeostasis.

2. The role of clock genes in the development and progression of breast cancer. Recent epidemiological evidence has emerged suggesting that prolonged shiftwork may increase the risk of certain cancers including breast cancer. These are provocative findings and demand confirmation or rebuttal by further study. We are investigating the role of clock genes on oncogene expression in normal mammary tissue and human breast cancer cells in xenografts and in vitro.

3. The role of clock genes in reproduction. It has been known for many decades that many reproductive processes are strongly influenced by daylength and time of day, especially in rodents and domestic ruminants. We are utilising the Bmal1 knockout mouse to study the role of clock genes in ovulation and early pregnancy.

4. The role of serotonin in mediating light entrainment of circadian rhythms. This project involves investigations of the cellular effects of serotonergic drugs on the rat SCN. It is hoped that this will lead to the development of drugs that will allow us to manipulate rhythmicity and overcome the physiological disruption of shiftwork and improve the sleep of the elderly.

Circadian Physiology Group

Recent Publications

1. M.J.Boden and D.J. Kennaway (2006) Circadian rhythms and reproduction. Reproduction 132 , 379-391.

2. D.J. Kennaway , J.A. Owens, A. Voultsios and T.J. Varcoe (2006) Functional central rhythmicity and light entrainment, but not liver and muscle rhythmicity are Clock independent. American Journal of Physiology 291 , R1172-80

3. B.T. Firth, I. Belan and D.J. Kennaway (2006) Persistence of a plasma melatonin rhythm in constant darkness and its inhibition by constant light in the sleepy lizard, Tiliqua rugosa . Journal of Pineal Research 41 , 15-20

4. P.J Ashwood, C.A. Crowther, K.J. Willson, R.R. Haslam, D.J. Kennaway , J.E. Hiller and J.S. Robinson (2005) Neonatal adrenal function following repeat dose prenatal corticosteroids: A randomised controlled trial. American Journal of Obstetrics and Gynecology 194 , 861-7.

5. D.J. Kennaway (2005) The role of circadian rhythmicity in reproduction. Human Reproduction Update 11 , 91-101.

6. J.L. Morrison, D.W. Rurak, C. Chien, D.J. Kennaway , N. Gruber, I.C. McMillen, and K.W. Riggs (2005) Maternal fluoxetine infusion does not alter fetal endocrine and biophysical circadian rhythms in pregnant sheep.Journal of the Society for Gynecological Investigation 12 , 356-364.

7. D.J. Kennaway , M.J. Boden and A. Voultsios (2005) Reproductive performance in female Clock D 19 mutant mice. Reproduction Fertility and Development 16 , 801-810.

8. D.J. Kennaway (2004) Resetting the suprachiasmatic nucleus clock. Frontiers in Bioscience 9 , 56-62.

9. H.R Wright, L.C Lack and D.J Kennaway (2004) Differential effects of light wavelength in phase advancing the melatonin rhythm. Journal of Pineal Research 36 , 140-144.

10. N.L. Rogers, D.F. Dinges, D.J. Kennaway and D. Dawson (2003) Potential action of melatonin in insomnia. Sleep 26 , 1058-9.

11. N.L. Rogers, D.J. Kennaway and D. Dawson. (2003) Neurobehavioural performance effects of daytime melatonin and temazepam administration. Journal of Sleep Research 12 , 207-212

12. T.J. Varcoe, D.J. Kennaway and A. Voultsios .(2003) Activation of 5-HT 2C receptors acutely induces per gene expression in the rat suprachiasmatic nucleus at night. Molecular Brain Research 119 , 192-200

13. D.J. Kennaway , T. J. Varcoe and V. J. Mau (2003) Rhythmic expression of clock and clock controlled genes in the rat oviduct. Molecular Human Reproduction 9 , 503-507.

14. D.J. Kennaway (2003) Drug effects on suprachiasmatic nucleus function. In Chronotherapeutics, ed . P. Redfern, Pharmaceutical Press. London . pp 343-368.

15. D.J. Kennaway , A. Voultsios, T.J. Varcoe and R.W. Moyer (2003) Melatonin and activity rhythm responses to light pulses in mice with the Clock mutation. Am Journal of Physiology 284 , R1231-1240.

16. D.J. Kennaway (2002) Programming of the fetal suprachiasmatic nucleus and subsequent adult rhythmicity. Trends in Endocrinology and Metabolism, 13 , 398-402.

17. D.J. Kennaway and H. Wright (2002) Melatonin and circadian rhythms. Current Topics in Medicinal Chemistry 2 , 199-209.

18. K. Lushington, R. Galka, L.N. Sassi, D.J. Kennaway and D. Dawson (2002) Extraocular light exposure does not phase shift saliva melatonin rhythm in sleeping subjects. Journal of Biological Rhythms 17 , 377-86.

19. S.A. Rowe and D.J. Kennaway (2002) Melatonin in rat milk and the likelihood of its role in postnatal maternal entrainment of rhythms. American Journal of Physiology 282 , R797-R804