Dr Grant Buchanan
|Org Unit||Medical Sciences|
|Telephone||+61 8 8222 7410|
|Mobile||+61 4 4728 8804|
QEH - Basil Hetzel Institute for Translationa
The Queen Elizabeth Hospital
Dr Buchanan leads a dynamic and contemporary research team, the Cancer Biology Group, at the Basil Hetzel Institute for Translational Research. This research group aims to fuse innovative molecular technology to pertinent clinical questions. The overall research objectives are to (i) provide a more holistic insight into the determinants of cancer initiation and progression, (ii) define comprehensive network models of nuclear receptor function in normal cells and in cancer, (iii) identify the inter-relationship between nuclear receptor networks, paracrine signalling and the cellular and tumour microenvironment, and (iv) generate and disseminate tools and reagents for nuclear receptor research.
During Dr Buchanan's PhD and early postdoctoral studies, he was mentored by Professors Villis Marshall and Wayne Tilley, who are internationally regarded for their work on androgen receptor (AR) in prostate cancer. Between 2006-2007, Dr Buchanan conducted the overseas component his CJ Martin Fellowship at the University of Southern California under the mentorship of Professors Gerry Coetzee, Mike Stallcup and Ron Ross (dec.). Working with that highly regarded and multidisciplinary team, Dr Buchanan established skills and resources in genome-scale analysis of steroid receptor action, cofactors, ChIP-chip, Chip-seq, transcription profiling, microarray, bioinformatics and network analysis, and established a set of strategic international collaborations. Returning to Australia, Dr Buchanan received one of only four nationally awarded Young Investigator Awards (2007) from the Prostate Cancer Foundation of Australia. In recognition of his research to date, in 2010 CIA Buchanan was awarded the Prostate Cancer Foundation of Australia National Young Researcher of the Year.
Dr Buchanan has held several prestigious research training fellowships; first from the Cancer Council of South Australia, a training award from the United States Department of Defense, a NHMRC CJ Martin Fellowship and lastly a NHMRC CDA Level A. Over the last 10 years, CIA Buchanan has supervised 7 Honours students (6/7 attaining first class; 2 as principal) and 8 PhD students (5 awarded, 3 current; 5 as principal).
1989-1992 Bachelor of Science
Institution: University of Tasmania
1993 Bachelor of Science with Honours
Institution: University of Adelaide
1998-2002 Doctor of Philosophy
Institution: Flinders University of South AustraliaThesis Title: Androgen receptor structure and function in prostate cancer
2010: Prostate Cancer Foundation of Australia National Young Researcher of the Year
2009: National Health and Medical Research Council Career Development Award (Level A)
2007: Prostate Cancer Foundation of Australia Young Investigator Award
2005: National Health and Medical Research Council CJ Martin Biomedical Fellowship
2005: Prostate Cancer Foundation of Australia Travel Award
2004: International Society of Endocrinology Travel Award
2004: Postdoctoral Traineeship Award, US Department of Defense
2003: The Cancer Council of South Australia Research Fellowship
2001: Lyn Wrigley Postgraduate Research Award
1999: Prostate Cancer Foundation of Australia Young Researcher Award (Overseas study grant)
1998: Flinders University Postgraduate Research Scholarship
1992: National Heart Foundation Scholarship
Buchanan G (CIA). PC030538: US Department of Defense Prostate Cancer Research Program (PCRP) of the Office of Congressionally Directed Medical Research Programs (CDMRP). Implication of Structural Features of TAU5 in the Androgen Receptor for Prostate Cancer Progression. 2004-2005. US$98,000
Buchanan G (CIA). BioInivation SA Proof of Commercial Concept Grant. Development of a Testosterone Bioassay. 2005-2007. AUD$35,850
Buchanan G (CIA). YI02. Prostate Cancer Foundation of Australia Young Investigator Award. A novel regulator of androgen receptor function in prostate cancer. 2008-2011. AUD$400,000
Buchanan G (CIA). Freemasons Foundation Center For Mens Health. Seeding grant. 2008-2010. AUD$250,000
Chopra S (CIA), Buchanan G, Pinnock C, Tamblyn D, Kopsaftis T. Androgen Receptor regulation of benign and malignant growth in the prostate. Foundation Daw Park, Repatriation General hospital. 2010, AUD$35,000
Buchanan G (CIA). Tilley WD, Green GL, Coetzee GA. DP110101101. Australian Research Council. Molecular dynamics of steroid receptor crosstalk. 2011-2013. $350,000
Buchanan G (CIA). Butler LM, Key T. PG2210. Prostate Cancer Foundation of Australia. Targeting chemokine signaling in prostate cancer. 2011-2012. $250,000
Pinnock C, Buchanan G, Chopra S, Kopsaftis T. Chemokine signalling in prostate cancer. Foundation Daw Park, Repatriation General hospital. 2011, AUD$23,000
Buchanan G (CIA), Taylor RA, Need EF. APP1032970. Cancer Australia's Priority-driven Collaborative Cancer Research Scheme in conjunction with the NHMRC (Cancer Australia / Prostate Cancer Foundation of Australia). Androgen receptor in the prostate cancer microenvironment. 2012-2014. $575,584
Pinnock C, Buchanan G, Kopsaftis T, Drew P. DNA methylation in prostate cancer: a pathway to the discovery of novel prognostic biomarkers and future therapies. Foundation Daw Park, Repatriation General hospital. 2012, AUD$19,900
Buchanan G (CIA). Brian and Maxine Newell Prostate Cancer Foundation. Equipment Grant. 2012. $27,500
2003-2005: Buchanan G. The Cancer Council of South Australia Research Fellowship
2006-2009: Buchanan G. ID:349565. National Health and Medical Research Council of Australia CJ Martin Biomedical Fellowship $309,984
2010-2013: Buchanan G. ID:627018. Androgen receptor action in the prostate cancer microenvironment. National Health and Medical Research Council Career Development Award (Level A). $377,000.
1. Tilley WD, Buchanan G, Hickey TE, Bentel JM. Mutations in the androgen receptor gene are associated with progression of human prostate cancer to androgen independence. Clin Cancer Res 2:277-285, 1996. IF 6.250; Cited 202.
2. Bentel JM, Buchanan G, Tilley WD. Androgen receptor gene mutations in prostate cancer. In: Naz R (ed) Frontiers in Bioscience; Prostate: Basic and Clinical Aspects.219-244, 1997. IF 2.989.
3. Buchanan G, Tilley WD. Androgen receptor structure and function in prostate cancer. In: Li JJ, Darling JR, Li SA (eds) Hormonal Carcinogenesis III. Springer-Verlag, New York, 333-341, 2000.
4. Park JJ, Irvine RA, Buchanan G, Koh SS, Park JM, Tilley WD, Stallcup MR, Press MF, Coetzee GA. Breast cancer susceptibility gene 1 (BRCAI) is a coactivator of the androgen receptor. Cancer Res 60:5946-5949, 2000. IF 7.672; Cited 89
5. Buchanan G, Yang M, Nahm SJ, Han G, Moore N, Bentel JM, Matusik RJ, Horsfall DJ, Marshall VR, Greenberg NM, Tilley WD. Mutations at the boundary of the hinge and ligand binding domain of the androgen receptor confer increased transactivation function. Mol Endocrinol 15:46-56, 2001. IF 5.337; Cited 52.
6. Han G, Foster BA, Mistry S, Buchanan G, Harris JM, Tilley WD, Greenberg NM Hormone status selects for spontaneous somatic androgen receptor variants that demonstrate specific ligand and cofactor dependent activities in autochthonous prostate cancer. J Biol Chem 276: 11204-11213, 2001. IF 5.581; Cited 63.
7. Buchanan G, Greenberg NM, Scher HI, Harris JM, Marshall VR, Tilley WD. Collocation of androgen receptor gene mutations in prostate cancer. Clin Cancer Res 7: 1273-1281, 2001. IF 6.250; Cited 73.
8. Buchanan G, Irvine RA, Coetzee GA, Tilley WD. Contribution of the androgen receptor to prostate cancer predisposition and progression. Cancer Metastasis Rev. 20:207-223, 2002. IF 6.766; Cited 59.
9. James AJ, Agoulnik IU, Harris JM, Buchanan G, Tilley WD, Marcelli M, Lamb DJ, Weigel NL. A novel androgen receptor mutant, A748T, exhibits hormone concentration-dependent defects in nuclear accumulation and activity despite normal hormone-binding affinity. Mol Endocrinol. 16:2692-705, 2002. IF 5.337; Cited 9.
10. Tilley WD, Buchanan G, and Coetzee GA. Androgen receptor signaling in prostate cancer. In: Henderson, BE, Ponder B, Ross RK (eds) Hormones, Genes and Cancer Oxford University Press, New York, 288-315, 2003. Cited 5.
11. Buchanan G, Craft PS, Yang M, Cheong A, Prescott J, Jia L, Coetzee GA, Tilley WD. PC-3 cells with enhanced androgen receptor signaling: a model for clonal selection in prostate cancer. Prostate. 60:352-66, 2004. IF 3.674; Cited 5.
12. Scher HI, Buchanan G, Gerald W, Butler LM, Tilley WD. Targeting the androgen receptor: improving outcomes for castration resistant prostate cancer. Endocr Relat Cancer. 11:459-76, 2004. IF 5.193; Cited 42.
13. Buchanan G, Yang M, Cheong A, Harris JM, Irvine RA, Lambert PF, Moore NL, Raynor M, Neufing PJ, Coetzee GA, Tilley WD. Structural and functional consequences of glutamine tract variation in the androgen receptor. Hum Mol Genet. 13:1677-92, 2004. IF 7.806; Cited 39.
14. Ricciardelli C, Choong CS, Buchanan G, Vivekanandan S, Neufing P, Stahl J, Marshall VR, Horsfall DJ, Tilley WD. Androgen receptor levels in prostate cancer epithelial and peritumoral stromal cells identify non-organ confined disease. Prostate. 63:19-28, 2005. IF 3.674; Cited 15.
15. Shen HC, Buchanan G, Butler LM, Prescott J, Henderson M, Tilley WD, Coetzee GA. GRIP1 mediates the interaction between the amino- and carboxyl-termini of the androgen receptor. Biol Chem, 386:69-74, 2005. IF 2.840; Cited 5.
16. Han G, Buchanan G, Harris JM, Ittmann M, Yu X, DeMayo FJ, Tilley WD, Greenberg NM. Mutation of the androgen receptor causes oncogenic transformation of the prostate. Proc Natl Acad Sci USA. 102:1151-1156, 2005. IF 9.598; Cited 55.
17. Makridakis NM, Buchanan G, Tilley WD, Reichardt JK. Androgen metabolic genes in prostate cancer predisposition and progression. Frontiers in Bioscience. 10:2892-2903, 2005.
18. Beekman KW, Buchanan G, Tilley WD, Scher HI. Anti-Androgen Withdrawal Syndromes: Pathophysiology and Clinical Implications. In: Partin AW (Ed) Prostate Cancer: Principles and Practice. Lippincott, Philadelphia.
19. Beekman KW, Buchanan G, Tilley WD, Scher HI. Beyond first line hormones: options for castration-resistant disease. In: Vogelzang NJ, Scardino PT, Shipley WU, Debruyne FMJ, Linehan WM (Eds). Comprehensive Textbook of Genitourinary Oncology (Third Edition). Wiley and Williams, Lippincott, Philadelphia, 330-340, 2005.
20. Buchanan G, Birrell SN, Ramsay K, Yang M, Harris JM, Simila HA, Peters AA, Moore NL, Bentel JM, Ricciardelli C, Horsfall DJ, Butler LM, Tilley WD. Decreased androgen receptor levels and receptor function in breast cancer contribute to the failure of response to medroxyprogesterone acetate. Cancer Res. 65:8487-8496, 2005. IF 7.672; Cited 15.
21. Butler LM, Centenera MM, Neufing PJ, Buchanan G, Choong CS, Ricciardelli C, Saint K, Lee MA, Ochnik A, Yang M, Brown MP and Tilley WD. Suppression of androgen receptor signalling in prostate cancer cells by an inhibitory receptor variant. Mol Endocrinol. 20:1009-24, 2006
22. Chmelar R, Buchanan G, Need EF, Tilley WD and Greenberg NM. Androgen receptor coregulators and their involvement in the development and progression of prostate cancer. Int J Cancer. 120:719-733, 2006.
23. Robzyk K, Oen H, Buchanan G, Butler LM, Tilley WD, Mandal AK, Rosen N & Caplan AJ. Uncoupling of Hormone-dependence from chaperone-dependence in the L701H mutation of the androgen receptor. Mol Cell Endocrionol. 268:67-74, 2007.
24. Birrell SN, Butler LM, Harris JM, Buchanan G, Tilley WD. Disruption of androgen receptor signaling by synthetic progestins may increase risk of developing breast cancer. FASEB J. 21:2285-93, 2007. IF 6.791, Cited 7.
25. Jariwala U, Prescott J, Jia L, Barski A, Pregizer S, Cogan JP, Arasheben A, Tilley WD, Scher HI, Gerald WL, Buchanan G, Coetzee GA, Frenkel B. Identification of novel androgen receptor target genes in prostate cancer. Mol Cancer. 6:39, 2007.
26. Buchanan G, Ricciardelli C, Harris JM, Prescott J, Yu ZC-L, Jia L, Butler LM, Marshall VR, Scher HI, Gerald WL, Coetzee GA, Tilley WD. Control of androgen receptor signaling in prostate cancer by the cochaperone small glutamine-rich tetratricopeptide repeat containing protein alpha. Cancer Res. 67:10087-10096, 2007. IF 7.672; Cited 4.
27. Buchanan G, Need EF, Bianco-Miotto T, Greenberg NM, Scher HI, Centenera, MM, Butler LM, Robins DM, Tilley WD. Insights from AR gene mutations. IN: Tindall DJ & Mohler JL (Eds) Androgen action in prostate cancer. Springer, New York (In press). IF N/A.
28. Jia L, Berman B, Jariwala U, Yan X, Cogan JP, Walters A, Chen T, Buchanan G, Frenkel B, Coetzee GA. Genomic androgen receptor-occupied regions with different functions, defined by histone acetylation, coregulators and transcriptional capacity. PlosONE 3(11):e3645, 2008. IF N/A.
29. Need EF, Scher HI, Moore NL, Cheong A, Ryan CJ, Wittert GA, Marshall VR, Tilley WD, Buchanan G. Collocation of AR Mutations in Prostate Cancer Reveals a Novel NTD Region Essential for N/C and p160 Interactions. Endocrinology. 150:2674-82, 2009. IF 5.045.
30. Baniwal SK, Khalid O, Sir D, Buchanan G, Coetzee GA, & Frenkel B. Repression of Runx2 by androgen receptor (AR) in osteoblasts and prostate cancer cells: AR binds Runx2 and abrogates its recruitment to DNA. Mol Endocrinol 23:1203-1214, 2009. IF 5.337.
31. *Peters AA, *Buchanan G, Ricciardelli C, Bianco-Miotto T, Harris JM, Segara D, Jia L, Moore LN, Henshell SM, Centenera MM, Coetzee GA, Sutherland GA, Butler LM & Tilley WD. Androgen receptor inhibits genomic activity of estrogen receptor-alpha and is prognostic of breast cancer outcome. Cancer Res 2009 69:6131-6140, 2009. (* Equal first authors) IF 7.672.
32. Need EF, O'Loughlin PD, Armstrong DT, Haren MT, Marting SA, Tilley WD, the Florey Adelaide Male Aging Study, Wittert GA, Buchanan G. Serum testosterone bioassay evaluation in a large male cohort. Clin Endocrinol (Oxf). 72:87-9, 2010. IF 3.370.
33. Diener KR, Need EF, Buchanan G, Hayball JD. TGF-beta signalling and immunity in prostate tumourigenesis. Expert Opin Ther Targets. 14:179-92, 2010. IF 4.038.
34. Bianco-Miotto T, Chiam K, Buchanan G, Jindal S, Day TK, Thomas M, Pickering M, O'Loughlin MA, Ryan NK, Raymond WA, Horvath LG, Kench JG, Stricker PD, Marshall VR, Sutherland RL Henshall SM, Gerald WL, Scher HI, Risbridger GP, Clements JA, Butler LM, Tilley WD; for the Australian Prostate Cancer BioResource. Global Levels of Specific Histone Modifications and an Epigenetic Gene Signature Predict Prostate Cancer Progression and Development Cancer. Epidemiol Biomarkers Prev; 19:2611-22, 2010.
35. Buchanan G, Need EF, Barrett, J. Bianco-Miotto TB, Thompson VC, Butler LM, Marshall VR, Tilley WD, Coetzee GA. Corepressor effect on androgen receptor activity varies with the length of the CAG encoded polyglutamine repeat and is dependent on receptor/corepressor ratio in prostate cancer cells. Mol Cell Endocrinol. 342:20-31, 2011.
36. Wang Q, Bailey CG, Ng C, Tiffen J, Thoeng A, Minhas V, Lehman ML, Hendy SC, Buchanan G, Nelson CC, Rasko JE, Holst J. Androgen receptor and nutrient signaling pathways coordinate the demand for increased amino acid transport during prostate cancer progression. Cancer Res, 71:7525-7536, 2011
37. Thompson VC, Day TK, Bianco-Miotto T, Selth LA, Han G, Thomas M, Buchanan G, Scher HI, Nelson CC, the Australian Prostate Cancer BioResource, Greenberg NM, Butler LM, Tilley WD. A gene signature identified using a mouse model of androgen receptor-dependent prostate cancer predicts biochemical relapse in human disease. Int J Cancer.131:662-672, 2012.
38. Lawrence MG, Stephens CR, Need EF, Lai J, Buchanan G, Clements JA. Long Terminal Repeats Act as Androgen-Responsive Enhancers for the PSA-Kallikrein Locus. Endocrinology. 153:3199-3210, 2012.
39. Trotta AP, Need EF, Butler LM, O'Loughlin MA, Coetzee GA, Tilley WD, Buchanan G. Sub-domain structure of the co-chaperone SGTA and activity of its androgen receptor client. J Mol Endo. 49:57-68, 2012.
40. Need EF, Selth LA, Harris TJ, Birrell SN, Tilley WD, Buchanan G. Transcriptional and genomic interplay between androgen receptor and estrogen receptor alpha in luminal breast cancer by ChIP-sequencing and expression profiling. Mol Endocrinol. 26:1941-52, 2012.
41. Moore NL, Buchanan G, Harris JM, Selth LA, Bianco-Miotto T, Hanson AR, Birrell SN, Butler LM, Hickey TE, Tilley WD. An androgen receptor mutation in the MDA-MB-453 cell line model of molecular apocrine breast cancer compromises receptor activity. Endocrine Relat Cancer. 19:599-613, 2012.
42. Chiam K, Ryan NK, Ricciardelli C, Day TK, Buchanan G, Ochnik AM, Murti K, Selth LA, Australian Prostate Cancer BioResource, Bulter LM, Tilley WD, Bianco-Miotto T. Characterization of the prostate cancer susceptibility gene KLF6 in human and mouse prostate cancers. Prostate. 73:182-93, 2013.
43. Abankwa D, Millard SM, Martel N, Choong CS, Yang M, Bulter LM, Buchanan G, Tilley WD, Leong GM. Ski-interacting protein (SKIP) interacts with the androgen receptor (AR) and enhances AR Amino- and Carboxy- terminal-dependent transcription. BMC Biochemistry (accepted)
Community Invited Speaker Presentations
• Eliminating the threat of prostate cancer. How prostate cancers become lethal and what we should do about it. The Queen Elizabeth Hospital Research Foundation Corporate Breakfast, Adelaide, South Australia, May 2012.
• Eliminating the threat of prostate cancer. How prostate cancers become lethal and what we should do about it. Brian and Maxine Newell Prostate Cancer Foundation Donors Meeting. Adelaide, South Australia, May 2012.
• Preventing prostate cancer from become lethal. The Hospital Research Foundation's Community Awareness Program. Adelaide, June 2012.
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