Steroid Receptor Biology
Research Group Head
Steroid hormones interact with their intracellular nuclear receptors (regulators of gene expression) which play a key role in the pathogenesis of many diseases including breast cancer and cardiovascular disease. Our research aims to provide key insights into the underlying activating mechanisms of nuclear receptors, particularly the adrenal steroid hormones aldosterone and cortisol and the reproductive hormones secreted by the ovary. By studying nuclear receptors we hope to identify new therapeutic targets for the treatment of these diseases. In addition, the group has initiated studies exploring an important endocrine cancer, thyroid cancer. This group works closely with the Endocrinology Unit of Monash Health.
The Steroid Receptor Biology Laboratory evolved from the group of Professor John Funder in the early 1990’s. It has been a world leader in work on aldosterone and the mineralocorticoid receptor through a series of contributions to understanding MR biology including: tissue distribution; identification of induced genes; functional studies of receptor-mediated transactivation; discovery of a ligand-dependent, ligand-specific interdomain interaction in the MR; identification and characterisation of MR co-regulatory molecules; and structure-function studies using novel chimeric approaches combined with molecular modelling. This group was the first to publish the genomic structure of the human MR gene in 1995 which enabled the mutational analysis of pseudohypoaldosteronism. This work has been complemented by ongoing studies using transgenic mice to define the tissue-specific roles of the MR in vivo. These studies have important implications for cardiac disease.
As a result of groundbreaking work on the reproductive hormone, inhibin, which Professor Henry Burger, in collaboration with Associate Professor Tom Jobling, Head of Gynaecology Oncology, Monash Health, identified a role of inhibin in the management of ovarian cancer. This lead to the laboratory developing the first systematic program of research to understand the molecular pathogenesis of granulosa cell tumours of the ovary.
Other innovative programs have included a collaboration for over 30 years with the Royal Children’s Hospital exploring the endocrinology and molecular pathogenesis of intestinal adaptation in the context of short bowel syndrome and, more recently, a novel research program in breast and thyroid cancer in collaboration with Hudson Institute colleagues as well as a series of national collaborations.
- Structure-function relationships of the mineralcorticoid receptor
- Molecular pathogenesis of granulosa cell tumours of the ovary
- Role of ERβ in folliculogenesis
- Ovarian phenotype of the IKKβ condition
- Molecular pathogenesis of thyroid cancer
- Non-classical roles of the mineralocorticoid receptor in reproductive tissues
Rogerson FM, Yao Y-Z, Young MJ, Fuller PJ (2014) Identification and characterisation of a ligand-selective mineralocorticoid receptor coactivator. FASEB Journal pii:fj.13-242479 Epub ahead of print.
Alexiadis A, Eriksson N, Jamieson S, Davis M, Drummond AE, Chu S, Clyne CD, Muscat GE, Fuller PJ (2011) Nuclear receptor profiling of ovarian granulosa cell tumors. Hormones and Cancer 2:157-69.
Jamieson S, Bützow R, Andersson N, Alexiadis M, Unkila-Kallio L, Heikinheimo M, Fuller PJ, Anttonen M (2010) The FOXL2 C134W mutation is characteristic of adult granulosa cell tumors of the ovary: independent confirmation from two centers. Modern Pathology 23:1477-85.
Pippal JB, Yao Y, Rogerson FM, Fuller PJ (2009) Structural and functional characterisation of the interdomain interaction in the mineralocorticoid receptor. Molecular Endocrinology 23:1360-1370.
Mond M, Alexiadis M, Eriksson N, Davis MJ, Muscat GEO, Fuller PJ, Gilfillan C (2014) Nuclear receptor expression in human differentiated thyroid tumors. Thyroid 24:1000-1011.