研究领域
Alternative Androgen Blockade: The dominant strategy in chemotherapy for prostate cancer is to prevent testosterone from reaching the prostate tumour and stimulating its growth, a scheme known as androgen blockade. Testosterone is the dominant male hormone; consequently removing it has a range of undesirable side effects. Our research is directed at providing a complementary approach to androgen blockade without the side effects.
Prevention of prostate cancer metastasis: Previous work in the hormone dependent cancer research program has identified the protease KLK4 as a potential target in preventing metastasis of prostate cancer cells. Accordingly we have developed inhibitors to this enzyme and these are being tested on prostate tumour cells growing in test tube conditions to gauge their effects on metastatic behaviour.
Enhancing hormone action: The hormone Ghrelin has a potential therapeutic role in treatment of eating disorders. We have designed and synthesised a novel form of the hormone with enhanced stability and increased potency when tested on cells grown under experimental conditions.
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Birrell SN, Butler LM, Harris J, Buchanan G, Tilley WD, (2007) Disruption of Androgen Receptor Signaling by Synthetic Progestins May Increase Risk of Developing Breast Cancer, The FASEB Journal p2285-2293
Buchanan G, Ricciardelli C, Harris J, Prescott J, Yu CL, Butler LM, Marshall V, Scher HL, Coetzee GA, Tilley WD, (2007) Control of Androgen Receptor Signaling in Prostate Cancer by the Cochaperone Small Glutamine-rich Tetratricopeptide Repeat Containing Protein Alpha, Cancer Research p10087-10096
Huston WM, Swedberg JE, Harris J, Walsh TP, Mathews SA, Timms P, (2007) The Temperature Activated HtrA Protease from Pathogen Chlamydia Trachomatis acts as both a Chaperone and Protease at 37, FEBS Letters p3382-3386
Lai J, Kedda M, Hinze K, Smith RL, Yaxley J, Spurdle AB, Morris CP, Harris J, Clements J, (2007) PSA/KLK3 AREI Promoter Polymorphism Alters Androgen Receptor Binding and is Associated with Prostate Cancer Susceptibility, Carcinogenesis p1032-1039
Buchanan G, Birrell SN, Peters AA, Bianco-Miotto T, Ramsay K, Cops EJ, Yang M, Harris J, Simila H, Moore NL, Bentel JM, Ricciardelli C, Horsfall DJ, Butler LM, Tilley WD, (2005) Decreased Androgen Receptor Levels and Receptor Function in Breast Cancer Contribute to the Failure of Response to Medroxyprogesterone Acetate, Cancer Research p8487-8496
Han G, Buchanan G, Ittmann M, Harris J, Yu X, DeMayo FJ, Tilley WD, Greenberg NM, (2005) Mutation of the Androgen Receptor Causes Oncogenic Transformation of the Prostate, Proceedings of the National Academy of Sciences of USA p1151-1156
Wansa KA, Harris JM, Yan G, Ordentlich P, Muscat GE, (2003) The AF-1 Domain of the Orphan Nuclear Recepror NOR-1 Mediates Trans-Activation, Coactivator Recruitment, and Activation by the Purine Anti-Metabolite 6-Mercaptorpurine, Journal of Biological Chemistry p24776-24790
Wan Y, Zheng YZ, Harris JM, Brown R, Waters M, (2003) Epitope Map for a Growth Hormone Receptor Agonist Monoclonal Antibody, MAb 263, Molecular Endocrinology p2240-2250
Harris J, Lau P, Chen SL, Muscat GE, (2002) Characterization of the Retinoid Orphan-Related Receptor-a Coactivator Binding Interface: A Structural Basis for Ligand-Independent Transcription, Molecular Endocrinology p998-1012
James AJ, Agoulnik IU, Harris J, Buchanan G, Tilley WD, Marcelli M, Lamb D, Weigel NL, (2002) A Novel Androgen Receptor Mutant, A748T, Exhibits Hormone Concentration-Dependent Defects in Nuclear Accumulation and Activity Despite Normal Hormone-Binding Affinity, Molecular Endocrinology p2692-2705