Prince Henry’s Institute

 

Evan Simpson

 

Appointments

• Senior Principal Research Fellow, NHMRC

• Honorary Professor, Department of Biochemistry and Molecular Biology, Monash University

• Group Leader, Victorian Breast Cancer Research Consortium Inc

Profile

Professor Simpson was PHI Director from 1999 to 2006. 

He is also Laboratory Director of the Victorian Breast Cancer Research Consortium. This consortium involves eight medical research institutes and was established in 1997 to conduct world class research into breast cancer.

Research Interests

Professor Simpson is a world leader in the field of oestrogen biosynthesis. His work has focussed on the study of aromatase, the enzyme responsible for oestrogen biosynthesis.

His group was the first to clone the gene encoding aromatase, and to show that tissue-specific regulation was under the control of tissue-specific promoters. His research led to the concept that oestrogen action in post-menopausal women is due to local production in sites such as the breast, bone and brain. This has led to the development of drugs for breast cancer therapy which specifically inhibit aromatase expression in the breast but spare other sites where it serves a critical role, such as in the bone, brain and blood vessels.

Professor Simpson's work also led to the creation of the first aromatase knockout (ArKO) mouse, which is a model of oestrogen insufficiency that compares with the phenotype of humans with natural mutations in aromatase. This resulted in the discovery of new and unexpected roles for oestrogens in both males and females, in particular the role of oestrogens in the maintenance of bone metabolism in men and the role of oestrogens in the regulation of energy homeostasis in both sexes.

His current research is focused on the role of oestrogen in several important health conditions, including obesity, diabetes, osteoporosis and, of course, breast cancer.

Expertise

Steroid biochemistry and molecular biology, transgenic models

 
Recent Achievements

• 2009 - Awarded Senior Principal Research Fellowship, NHMRC

• 2006 - Elected as a Fellow of the Australian Academy of Science

• 2006 - Recipient of the Nancy Brinker Award from the Susan G Komen Breast Cancer Foundation

• 2005 - Recipient of the Roy O Greep Lecturer Award from the US Endocrine Society

• Recipient of the Asia-Oceania Medal from the UK Society for Endocrinology

• 2003 - Listed as one of only 3 Australians in Thompson ISI Most Highly Cited in the area of biology and biochemistry

• 2002 - Awarded the Earl Plunkett Lecturer of the University of Western Ontario

 

Current Research

• Obesity and breast cancer risk

• Insulin resistance in the aromatase knockout mouse

 

Selected Publications

Brown KA, McInnes KJ, Hunger NI, Oakhill JS, Steinberg GR, Simpson ER. Subcellular localization of cyclic AMP-responsive element binding protein-regulated transcription coactivator 2 provides a link between obesity and breast cancer in postmenopausal women. Cancer Res. 2009 Jul 1;69(13):5392-9.

McInnes KJ, Corbould A, Simpson ER, Jones ME. Regulation of AMPK and lipogenesis by androgens contributes to visceral obesity in an estrogen deficient state. Endocrinology 147(12):5907-13 (2006).

Le May C, Chu K, Ku M, Ortega CS, Simpson ER¸Korach KS, Tsai MJ, Mauvais-Jarvis F. Estrogens protect pancreatic beta cells from apoptosis and prevent insulin-deficient diabetes mellitus in mice. Proceedings from the Natinoal Academy of Sciences (USA) 24:9232-9237 (2006).

Hill RA, McInnes KJ, Gong EC, Jones ME, Simpson ER, Boon WC. Estrogen deficient male mice develop compulsive behaviour. Biol Psychiatry 61(3):359-66 2007

Safi R, Kovacic A, Gaillard S, Murata Y, Simpson ER, McDonnell DP, Clyne CD. Coactivation of LRH-1 by PGC-1 an aromatase promoter II and its activation by RXR suggest a novel target for breast-specific antioestrogen therapy. Cancer Research 65(24):11762-11770 (2005)

Zhou J, Suzuki T, Kovacic A, Saito R, Miki Y, Ishida T, Moriya T, Simpson ER, Sasano H, Clyne CD. Interactions between prostaglandin E2, liver receptor homologue-1, and aromatase in breast cancer. Cancer Res 65:657-663, 2005

Simpson ER, Misso M, Hewitt KN, Hill RA, Boon WC, Jones MEE, Kovacic A, Zhou J, Clyne CD. Estrogens: The good, the bad, and the unexpected. Endocrine Reviews 26:322-330, 2005

Maffei L, Murata Y, Rochira V, Tubert G, Aranda C, Vazques M, Clyne CD, Davis S, Simpson ER, Carani C. Dysmetabolic syndrome in a man with a novel mutation of the aromatase gene:effects of testosterone, alendronate and estradiol treatment. Journal of Clinical Endocrinology and Metabolism. 89:61-70 (2004)

Hewitt KN, Pratis K, Jones ME, Simpson ER. Estrogen replacement reverses the hepatic steatosis phenotype in the male aromatase knockout (ArKO) mouse. Endocrinology 145(4)1842-1848 2004

Hill RA, Pompolo S, Jones MEE, Simpson ER, Boon WC. Estrogen deficiency leads to apoptosis in dopaminergic neurons in the medial pre-optic area and arcuate nucleus of male mice. Mol Cell Neuroscience 27:466-476, 2004

Shim GJ, Warner M, Kim HJ, Andersson S, Liu L, Ekman J, Imamo O, Jones ME, Simpson ER, Gustafsson JA. Aromatase-deficient mice spontaneously develop a lymphoproliferative autoimmune disease resembling Sjogren syndrome. Proc. Natl. Acad. Sci USA 24:12628-12633, 2004

Yan M, Jones ME, Hernandez M, Liu D, Simpson ER, Chen C. Functional modification of pituitary somatotropes in the aromatase knockout mouse and the effect of estrogen replacement. Endocrinology, 145:604-612, 2004

Kovacic A, Speed CJ, Simpson ER, Clyne CD. Inhibition of aromatase transcription via promoter II by short heterodimer partner in human preadipocytes.Mol Endocrinol 18:252-259 (2004)

Britt KL, Stanton PG, Misso M, Simpson ER, Findlay JK. The effects of estrogen on the expression of genes underlying the differentiation of somatic cells in the murine gonad. Endocrinology 145:3950-3960, 2004

Watanabe M, Simpson ER, Pathirage N, Nakajin S, Clyne CD. Aromatase expression in the human fetal osteoblastic cell line SV-HFO. J Mol Endocrinol 32(2) 533-545, 2004

McCullough LD, Blizzard K, Simpson ER, Oz OK, Hurn PD. Aromatase cytochrome P450 and extragonadal estrogen play a role in ischemic neuroprotection. J. Neuroscience 23:8701-8705 (2003)

Misso ML, Murata Y, Boon WC, Jones ME, Britt KL, Simpson ER. Cellular and molecular characterization of the adipose phenotype of the aromatase-deficient mouse. Endocrinology. 144:1414-1480, (2003)

Kimura M, Sudhir K, Jones M, Simpson ER, Jefferis A-M, Chin-Dusting JPF. Impaired acetycholine induced release of nitric oxide in the aorta of male aromatase knockout (ArKO) mice:regulation of nitric oxide production by endogenous sex hormones in males. Circ. Res 93:1267-1271 (2003)

Britt KL, Kerr J, O'Donnell L, Jones MEE, Drummond AE, Davis SR, Simpson ER, Findlay JK. Estrogen regulates development of the somatic cell phenotype in the eutherian ovary. FASEB Journal. 16(11):1389-1397, 2002.

Clyne CD, Speed CJ, Zhou J, Simpson ER. Liver receptor homologue-1 (LRH-1) regulates expression of aromatase in preadipocytes. Journal of Biological Chemistry 277:20591-20597, 2002.

Rubin GL, Duong J, Gong C, Clyne CD, Simpson ER. Ligands for the peroxisome proliferator-activated receptor and the retinoid X receptor inhibit aromatase cytochrome P450 (CYP19) expression mediated by promoter II in human breast adipose. Endocrinology 143:2863 2871, 2002.

Robertson KM, O'Donnell L, Simpson ER, Jones MEE. The phenotype of the ArKO mouse reveals a role for dietary phytoestrogens impact on testicular function. Endocrinology 143:8 2913- 2002

Simpson ER, Clyne CD, Rubin GL, Boon WC, Robertson KM, Britt KL, Speed CL, Jones MEE. Aromatase - A brief review. Ann. Rev. Physiol. 64:93-127, 2002