Molecular Endocrinology and Musculoskeletal Research Group

Research Overview

We are studying the biological mechanisms underlying osteoporosis, muscle wasting and obesity, which are all disorders of hormonal action.  Osteoporosis affects one in two women and one in three men over the age of 60, leading to bone fractures; muscle wasting is a significant problem in the elderly population and in patients suffering cancer, burns and chronic illness; and obesity is reaching epidemic proportions in Western populations; and all these diseases cause significant morbidity in the population worldwide.

Our group is using unique and cutting-edge genetically modified mouse models to study the mechanisms involved in these diseases.  Our research combines the power of physiology and molecular biology to gain insight into the cellular and molecular pathways through which androgens and calcium-regulating hormones act. Knowledge gained from our research will help build Australia’s health research skills and will allow us to better understand the pathophysiology osteoporosis, muscle wasting and obesity, which is crucial to developing improved therapies for these diseases.

Current projects:

  • Characterising the physiological role of the calcitonin receptor in bone and calcium homeostasis.
  • Determining the mechanism by which the male sex hormone, testosterone, acts to decrease fat mass.
  • Investigating the efforts of cross-sex hormone therapy on bone during puberty and adulthood.

Read more about Rachel's work below:

  1. 'Hormones and Bones', A/Prof Rachel Davey discusses her research into metabolic bone diseases which has a focus on the physiological role of hormones to increase new bone growth.
  2. 'Hope for older men', A/Prof Rachel Davey presents her research into discovering a new pathway tor reduce weight gain in men with low testosterone levels.

Staff

  • Dr Varun Venkatesh, Post doctoral Scientist
  • Ms Sue Golub, Senior  Research Assistant
  • Ms Tian Nie, PhD student

Collaborators

  • Professor Jeffrey Zajac
  • Associate Professor Mathis Grossmann
  • Professor David Findlay, Dept of Orthopaedics and Trauma, University of Adelaide, SA, Australia
  • Professor Dirk Vanderschueren, Leuven Catholic University, Belgium
  • Professor Jack Jhamandas, University of Alberta, Canada
  • Dr Svetlana Reilly, University of Oxford, UK
  • Professor Merry-Jo Oursler, Mayo Clinic, Minnesota, USA
  • Professor Kristine Wiren, Oregon Health and Sciences University, Oregon, USA
  • Dr Ajith Vasanthakumar and Dr Axel Kallies, Peter Doherty Institute, Vic, Australia

Funding

  • Ian Potter Foundation
  • Sir Edward Dunlop Medical Research Foundation
  • Austin Health Medical Research Foundation
  • The Les and Eva Erdi Humanitarian Charitable Foundation
  • H.T. Pamphilon Fund

Research Outcomes

Research Publications

Clarke MV, Russell PK, Zajac JD, Davey RA. The androgen receptor in the hypothalamus positively regulates hind-limb muscle mass and voluntary activity in male mice. Journal of Steroid Biochemistry and Molecular Biology, 2019 189:187-194.

Russell PK, Mangiafico S, Fam BC, Clarke MV, Marin ES, Andrikopoulos S, Wiren KM, Zajac JD, Davey RA. The androgen receptor in bone marrow progenitor cells negatively regulates fat mass. Journal of Endocrinology, 2018, 237(1):15-27.

Cheung AS, de Rooy C, Levinger I, Rana K, Clarke MV, How JM, Garnham A, McLean C, Zajac JD, Davey RA*, Grossmann MG* (*Equal senior authors).  Actin alpha cardiac muscle1 gene expression is upregulated in the skeletal muscle of men undergoing androgen deprivation therapy for prostate cancer.  Journal of Steroid Biochemistry and Molecular Biology, 2017, 174:56-64.

Davey RA, Clarke MV, Russell PK, Rana K, Seto J, Roeszler KN, How JMY, Chia LY, North K, Zajac JD. Androgen action via the Androgen Receptor in neurons within the brain positively regulates muscle mass in male mice. Endocrinology, 2017, 158(10):3684-3695.

Davey RA and Grossmann M. Androgen Receptor Structure, Function and Biology: From Bench to Bedside. The Clinical Biochemist Reviews, 2016, 37(1):3-15.

Clarke MV, Russell PK, Findlay DM, Sastra S, Anderson PH, Skinner JP, Atkins GJ, Zajac JD, Davey RA. A role for the calcitonin receptor to limit bone loss during lactation in female mice by inhibiting osteocytic osteolysis. Endocrinology, 2015, 156(9):3203-3214.

Russell PK, Clarke MV, Cheong K, Anderson PH, Morris HA, Wiren KM, Zajac JD, Davey RA.  Androgen receptor action in osteoblasts in male mice is dependent on their stage of maturation. Journal of Bone and Mineral Research, 2015, 30(5): 809-823.

Davey RA and Findlay DM.  Calcitonin – Physiology or Fantasy? The Journal of Bone and Mineral Research Invited Review.  2013, 28(5): 973-979.

Turner AG, Tjahyono F, Chiu WSM, Skinner J, Sawyer R, Moore AJ, Morris HA, Findlay DM, Zajac JD, Davey RA.  “The role of the calcitonin receptor in protecting against induced hypercalcemia is mediated via its actions in osteoclasts to inhibit bone resorption”. Bone  2011, 48, 354-361.

Pang TPS, Clarke MV, Ghasem-Zadeh A, Lee NKL, Davey RA*, MacLean* (Equal senior authors). A physiological role for androgen actions in the absence of androgen receptor DNA binding activity. Molecular and Cellular Endocrinology, 2012, 348: 189-197.

Chiang C, Chiu MWS, Moore AJ, Ghasem-Zadeh A, McManus JF, Ma C, Doust EA, Seeman E, Clemens T, Morris HA, Zajac JD, Davey RA. “Mineralization and Bone Resorption are Regulated by the Androgen Receptor in Male Mice.” JBMR 2009 24(4), 621-631.

MacLean HE, Moore AJ, Sastra SA, Morris HA, Ghasem-Zadeh A, Rana K, Axell AM, Notini AJ, Handelsman DJ, Seeman E, Zajac JD, Davey RA.  “DNA-binding-dependent androgen receptor signaling contributes to gender differences and has physiological actions in males and females”.  Journal of Endocrinology  2010, 206, 93-103.

Davey, R.A., Turner, A., McManus, J.F., Chiu, M.W.S., Tjahyono, F., Moore, A.J., Atkins, G.J., Anderson, P.H., Ma, C., Glatt, V., MacLean, H.E., Vincent, C., Bouxsein, M., Morris, H.A., Findlay, D.M., Zajac, J.D.  The Calcitonin Receptor Plays a Physiological Role to Protect Against Hypercalcemia in Mice. JBMR, 2008  23(8):1182-93.

Notini, A.J., McManus, J.F., Moore, A.J., Bouxsein, M., Jimenez, M., Chiu, W.S.M., Glatt, V., Kream, B.E., Handelsman, D.J., Morris, H.A., Zajac, J.D. & Davey, R.A. Osteoblast-specific deletion of exon 3 of the androgen receptor gene results in trabecular bone loss in adult male mice. Journal of Bone and Mineral Research, 2007 22(3):347-56.

Chiu, W.S.M., McManus, J.F., Notini, A.J., Cassady, A.I., Zajac, J.D. & Davey, R.A. Transgenic mice that express Cre recombinase in osteoclasts. Genesis, 39 (3) 2004, 178-85.

Davey, R.A.*, Dacquin, R.*, Laplace, C., Levasseur, R., Morris, H.A., Goldring, S.R., Gebre-Medhin, S., Galson, D.L., Zajac, J.D. & Karsenty, G. (*Equal first authors) Amylin inhibits bone resorption while the calcitonin receptor controls bone formation in vivo. Journal of Cell Biology, 164 (4) 2004, 509-514.