Professor Peter Leedman, MBBS, PhD, FRACP, FAHMS


Director Professor Peter Leedman
Laboratory Head, Laboratory for Cancer Medicine

E:   peter.leedman@perkins.uwa.edu.au
T:   +61 8 6151 0700

Profile
Professor Peter Leedman completed medicine at The University of Western Australia (UWA), then trained in endocrinology at Royal Melbourne Hospital in the mid-1980s. He completed his PhD at the Walter and Eliza Hall Institute in Melbourne with Len Harrison on autoimmune thyroid disease from 1987-1991. From 1991-1994 he was a Lucille P Markey Fellow with Bill Chin, a Howard Hughes Investigator in the Division of Genetics, Brigham and Women's hospital, Harvard Medical School in Boston where he worked on the molecular mechanisms of thyroid hormone action. He returned to Perth in 1994 as a Senior Lecturer in Medicine at UWA and became a Professor in 2003. Professor Leedman is Director of the Harry Perkins Institute of Medical Research, an endocrinologist, Head of the Laboratory for Cancer Medicine and Chairman of Linear Clinical Research Ltd, a state-of-the-art 32-bed early phase clinical trials facility, which is a wholly owned subsiduary of the Perkins. 

Research overview
He has had a long-term interest in understanding how hormones act at the molecular level, with a focus on RNA biology and interactions between RNA and proteins, and how this information can be harnessed to personalise cancer therapy. His laboratory has focused on the mechanisms regulating expression of key therapeutic targets in hormone-dependent cancers (breast and prostate cancer) and more recently in poor prognostic tumours, including liver, head and neck cancer as well as advanced melanoma. His team has identified key functional roles for a number of small RNAs, called microRNAs, in these tumours and uncovered several new members of a complex network of RNA-biding nuclear receptor hormone coregulators. His laboratory has focused on applying advances in understanding these molecular mechanisms to the development of novel therapeutics. His published research shows that microRNA-7 can knock-out an essential growth receptor for cancer, known as the epidermal growth factor receptor (EGFR), as well as its associated signalling pathways that promote cancer development. The EGFR is a major target for therapy in liver cancer, because it is often associated with disease progression, resistance to chemotherapy and radiation therapy. Recent studies have shown that microRNA-7 is a potent inhibitor of the EGFR and resultant growth in liver cancer. The team’s findings have led to the establishment of miReven, a biopharmaceutical company focused on developing microRNA-7 into a new treatment for liver cancer.



Selected publications

  1. Kabir TD, Ganda C, Brown RAM, Beveridge DJ, Richardson KL, Chaturvedi V, Epis MR, Wintle L, Kalinowski FC, Kopp C, Stuart LM, Yeoh G, George J, Leedman PJ. A miR-7/GAS6/TYRO3 axis regulates the growth and invasiveness of sorafenib-resistant cells in human hepatocellular carcinoma. Hepatology 2018, 67: 216-231.
  2. Brown RAM, Epis MR, Horsham JL, Kabir TD, Richardson KL, Leedman PJ. Total RNA extraction from tissues for microRNA and target gene expression analysis: not all kits are created equal. BMC Biotechnol. 2018, 18(1):16.
  3. Epis MR, Giles KM, Beveridge DJ, Richardson KL, Candy PA, Stuart LM, Bentel J, Cohen RJ, Leedman PJ. miR-331-3p and Aurora Kinase inhibitor II co-treatment suppresses prostate cancer tumorigenesis and progression. Oncotarget, 2017, 8; 55116-55134.
  4. Giles KM, Brown RAM, Ganda C, Podgorny MJ, Candy PA, Wintle LC, Richardson KL, Kalinowski FC, Stuart LM, Haass NK, Herlyn M, Leedman PJ. microRNA-7-5p inhibits cell proliferation and metastasis of melanoma by targeting RelA. Oncotarget, 2016, 7(22): 31663-80.
  5. Horsham JL, Ganda C, Kalinowski FC, Brown RAM, Epis MR, Leedman PJ. microRNA-7: a microRNA with diverse roles in development and disease. Int J Biochem Cell Biology, 2015, 69: 215-24.
  6. Oh TGC, Bailey P, Goode J, Eriksson N, Funder JW, Fuller PF, Simpson ER, Tilley WD, Leedman PJ, Clarke CL, Dowhan DH, Muscat GEO. Protein Arginine Methyltransferase 2-dependent gene expression is associated with breast cancer survival outcomes: PRMT2 and RORg expression are inversely correlated. Molecular Endocrinology 2014, 28: 1166-85.
  7. Muscat G, Eriksson N, Byth K, Loi S, Graham D, Jindal S, Davis M, Clyne C, Funder JW, Simpson ER, Ragan M, Kuczek E, Fuller PJ, Tilley W, Leedman PJ, Clarke C. Differential nuclear hormone receptor expression in human breast cancer: 8 nuclear receptors including the NR4A subgroup and EAR2 are highly expressed in breast cancer cohorts. Molecular Endocrinology 2013, 27: 350-365.
  8. Redfern AD, Colley SM, Beveridge D, Ikeda N, Epis M, Li X, FouldsC, Stuart LM, Barker A, Russell VJ, Ramsay K, Kobelke SJ, Li X, Hatchell EC, Payne C, Giles KM, Messineo A, Gatignol A, Lanz RB, O'Malley BW, Leedman PJ. 2013. RISC Proteins PACT, TRBP, and Dicer are SRA-binding nuclear receptor coregulators. Proceedings of the National Academy of Sciences USA 110:6536-6541. [NCBI PubMed Entry]
  9. Kalinowski F, Giles KM, Candy PA, Ali A, Ganda C, Epis MR, Webster RJ, Leedman PJ. 2012. microRNA-7 regulates EGFR signaling and sensitivity of head and neck cancer cells to erlotinib. PLoS One 7(10):e47067. [NCBI PubMed Entry]
  10. Epis M, Giles KM, Candy PA, Barker A, Cohen RJ, Leedman PJ. 2012. Regulation of expression of deoxyhypusine hydroxylase (DOHH), the enzyme that catalyzes the activation of eIF5A, by miR-331-3p and miR-642-5p in prostate cancer cells. Journal of Biological Chemistry 287:35251-35259. [NCBI PubMed Entry]
  11. Webster RJ, Giles KM, Price KJ, Zhang PM, Mattick JS, Leedman PJ. 2009. Regulation of epidermal growth factor receptor signaling in human cancer cells by microRNA-7. The Journal of Biological Chemistry 284(9):5731-5741. [NCBI PubMed Entry]
  12. Yu D, Tan AH, Hu X, Athanasopoulos V, Simpson N, Silva DG, Hutloff A, Giles KM, Leedman PJ, Lam KP, Goodnow CC, Vinuesa CG. 2007. Roquin represses autoimmunity by limiting inducible T-cell co-stimulator messenger RNA. Nature 450(7167):299-303. [NCBI PubMed Entry]
  13. Hatchell EM, Colley S, Beveridge DJ, Epis MR, Stuart LM, Giles KM, Redfern AD, Miles LEC, Barker A, MacDonald L, Arthur PG, Lui JCK, Golding J, McCulloch RK, Metcalf C, Wilce JA, Wilce MCJ, Lanz RB, O'Malley BW, Leedman PJ. 2006. SLIRP, a small SRA-binding protein, is a nuclear receptor co-repressor. Molecular Cell 22:657-68. [NCBI PubMed Entry]
  14. Giles KM, Daly JM, Beveridge DJ, Thomson AM, Voon D, Furneaux HM, Jazayeri JA, Leedman PJ. 2003. The 3'-Untranslated Region of p21WAF1 mRNA is a complex cis-acting element bound by multiple RNA-binding proteins from breast cancer cells, including HuR and poly(C)-binding protein (CP1). The Journal of Biological Chemistry 278:2937-46. [NCBI PubMed Entry]
  15. Yeap BB, Voon D, Vivian J, McCulloch, Thomson AM, Furneaux H, Wilce MJ, Wilce JA, Leedman PJ. 2002. Novel binding of HuR and poly(C)-binding protein to a conserved UC-rich motif within the 3'-untranslated region of the androgen receptor messenger RNA. The Journal of Biological Chemistry 277:27183-92. [NCBI PubMed Entry]
  16. Leedman PJ, Faulkner-Jones B, Cram D, Harrison P, West J, Simpson R, Coppel R, Harrison LC. 1993. Cloning from the thyroid of a protein related to actin-binding protein that is recognized by Graves' disease immunoglobulins. Proceedings of the National Academy of Sciences of the USA 90:5994-8. [NCBI PubMed Entry]
  17. Kielczynski W, Harrison LC, Leedman PJ. 1991. Direct evidence that ganglioside is an integral component of the thyrotropin receptor. Proceedings of the National Academy of Sciences of the USA 88:1991-5. [NCBI PubMed Entry]
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