Centre for Cancer Biology-Gene Regulation Laboratory

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Staff
Research Interests
Selected Recent Publications
Available Student Projects

General Enquiries

Ms Anna Nitschke
PA to Prof. Angel Lopez

Centre for Cancer Biology
SA Pathology
PO Box 14 Rundle Mall
Adelaide SA 5000
AUSTRALIA

Tel: 61 8 8222 3422
Fax:61 8 8232 4092

Email: Anna.Nitschke@health.sa.gov.au

Gene Regulation Laboratory

Head

Professor Greg Goodall

Address	Centre for Cancer Biology SA Pathology Frome Road, Adelaide SA 5000, Australia
Phone	+61 8 8222 3430
Fax	+61 8 8232 4092
Email	Greg.Goodall@health.sa.gov.au

Affiliations: Professor , Discipline of Medicine, University of Adelaide

Qualifications: B.Sc. (Adelaide), PhD (Adelaide)

Experience:

1982	Postdoctoral Fellow, Roche Institute of Molecular Biology, Nutley, New Jersey, USA
1983	Postdoctoral Fellow, Department of Biochemistry, The University of Adelaide, Adelaide, Australia
1984-85	Postdoctoral Fellow, Roche Institute of Molecular Biology, Nutley, New Jersey, USA
1986	Research Associate, Department of Biochemistry, Cornell University Medical College, New York, USA
1987-89	Postdoctoral Fellow, Friedrich Miescher Institut, Basel, Switzerland
1990	Research Fellow, Friedrich Miescher Institut, Basel, Switzerland

Staff

Postdoctoral Research Scientists	Telephone	Email
Dr Joanne Attema	8222 3479	Joanne.Attema@health.sa.gov.au
Dr Cameron Bracken	8222 3432	Cameron.Bracken@health.sa.gov.au
Dr Philip Gregory	8222 3432	Philip.Gregory@health.sa.gov.au
Dr Emily Paterson	8222 3479	Emily.Paterson@health.sa.gov.au
Dr Anna Tsykin	8222 3479	Anna.Tsykin@health.sa.gov.au
Dr Josephine Wright	8222 3023	Josephine.Wright@health.sa.gov.au

Research Assistants	Telephone	Email
Matthew Anderson	8222 3432	Matthew.Anderson@health.sa.gov.au
Andrew Bert	8222 3473	Andrew.Bert@health.sa.gov.au
Suraya Roslan	8222 3409	Suraya.Roslan@health.sa.gov.au
Rosemary Sladic	8222 3409	Rosemary.Sladic@health.sa.gov.au

PhD Students	Telephone	Email
Natasha Kolesnikoff	8222 3712	Natasha.Kolesnikoff@health.sa.gov.au
Yat Yuen Lim	8222 3432	YatYuen.Lim@health.sa.gov.au
Daniel Thomson	8222 3432	Daniel.Thomson@health.sa.gov.au

Honor Students	Telephone	Email
Victoria Arnet	8222 3409	Victoria.Arnet@health.sa.gov.au
Phillip Nguyen (Co-supervised with Prof Angel Lopez)	8222 3409	Phillip.Nguyen@health.sa.gov.au

Technical Officer	Telephone	Email
Narrelle Mancini	8222 3409	Narrelle.Mancini@health.sa.gov.au

Back Row: Rosemary Sladic, Narrelle Mancini, Andrew Bert, Cameron Bracken, Natasha Kolesnikoff, Suraya Roslan. Front Row: Matthew Anderson, Anna Tsykin, Emily Paterson, Josephine Wright, Daniel Thomson, Greg Goodall, Yat Yuen (Eddy) Lim, Philip Gregory.

Research Interests

MicroRNAs are small RNA molecules that are involved in regulating many key processes in the cell through posttranscriptional regulation of gene expression. Using microRNA microarrays, which we developed in house, we have discovered that the miR-200 microRNA family controls epithelial to mesenchymal transition (EMT), which is considered to be a key step in tumour metastasis. Metastasis, which is the major cause of death from cancer, involves the dissociation and migration of cells away from the primary tumour. To achieve this, the tumour cells recapitulate the EMT process that normally occurs in early development, in which the cells that are normally tightly associated with their neighbouring cells acquire the features of mesenchymal cells, which can migrate.

We have found in our in-vitro models that the microRNAs have to be turned off to allow the cells to become migratory and invasive. We have also found that if we enforce expression of the microRNAs, we can block the EMT process and even convert the migratory cells back to non-migratory, ‘epithelial’ cells. In ongoing work we are examining the mechanisms that control production and loss of the microRNAs; identifying the gene targets of the microRNAs; examining human tumours for involvement of the microRNAs in invasion and metastasis and using in vitro and in vivo models to identify the pathways through which they operate. We are also using microRNA microarrays to identify the involvement of microRNAs in other important biological processes and diseases.

Selected Recent Publications

Bracken, C. P., J. M. Szubert, T. R. Mercer, M. E. Dinger, D. W. Thomson, J. S. Mattick, M. Z. Michael and G. J. Goodall. "Global analysis of the mammalian RNA degradome reveals widespread miRNA-dependent and miRNA-independent endonucleolytic cleavage." Nucleic Acids Res 39: 5658-5668. (2011)

Gregory, P. A., C. P. Bracken, E. Smith, A. G. Bert, J. A. Wright, S. Roslan, M. Morris, L. Wyatt, G. Farshid, Y. Y. Lim, G. J. Lindeman, M. F. Shannon, P. A. Drew, Y. Khew-Goodall and G. J. Goodall. "An autocrine TGF-beta/ZEB/miR-200 signaling network regulates establishment and maintenance of epithelial-mesenchymal transition." Mol Biol Cell 22: 1686-1698. (2011)

Matsushima, K., H. Isomoto, N. Yamaguchi, N. Inoue, H. Machida, T. Nakayama, T. Hayashi, M. Kunizaki, S. Hidaka, T. Nagayasu, M. Nakashima, K. Ujifuku, N. Mitsutake, A. Ohtsuru, S. Yamashita, M. Korpal, Y. Kang, P. A. Gregory, G. J. Goodall, S. Kohno and K. Nakao. "MiRNA-205 modulates cellular invasion and migration via regulating zinc finger E-box binding homeobox 2 expression in esophageal squamous cell carcinoma cells." J Transl Med 9: 30. (2011)

McInnes, N., T. J. Sadlon, C. Y. Brown, S. Pederson, M. Beyer, J. L. Schultze, S. McColl, G. J. Goodall and S. C. Barry. "FOXP3 and FOXP3-regulated microRNAs suppress SATB1 in breast cancer cells." Oncogene (2011)

Terao, M., M. Fratelli, M. Kurosaki, A. Zanetti, V. Guarnaccia, G. Paroni, A. Tsykin, M. Lupi, M. Gianni, G. J. Goodall and E. Garattini. "Induction of miR-21 by retinoic acid in estrogen receptor-positive breast carcinoma cells: biological correlates and molecular targets." J Biol Chem 286: 4027-4042. (2011)

Thomson, D. W., C. P. Bracken and G. J. Goodall. "Experimental strategies for microRNA target identification." Nucleic Acids Res 39: 6845-6853. (2011)

Wang, Z., Y. Zhao, E. Smith, G. J. Goodall, P. A. Drew, T. Brabletz and C. Yang. "Reversal and prevention of arsenic-induced human bronchial epithelial cell malignant transformation by microRNA-200b." Toxicol Sci 121: 110-122. (2011)

Yang, Y., Y. H. Ahn, D. L. Gibbons, Y. Zang, W. Lin, N. Thilaganathan, C. A. Alvarez, D. C. Moreira, C. J. Creighton, P. A. Gregory, G. J. Goodall and J. M. Kurie. "The Notch ligand Jagged2 promotes lung adenocarcinoma metastasis through a miR-200-dependent pathway in mice." J Clin Invest 121: 1373-1385. (2011)

Khew-Goodall, Y. and G. J. Goodall. "Myc-modulated miR-9 makes more metastases." Nat Cell Biol 12: 209-211. (2010)

Liu, B., L. Liu, A. Tsykin, G. J. Goodall, J. E. Green, M. Zhu, C. H. Kim and J. Li. "Identifying functional miRNA-mRNA regulatory modules with correspondence latent dirichlet allocation." Bioinformatics 26: 3105-3111. (2010)

Mercer, T. R., M. E. Dinger, C. P. Bracken, G. Kolle, J. M. Szubert, D. J. Korbie, M. E. Askarian-Amiri, B. B. Gardiner, G. J. Goodall, S. M. Grimmond and J. S. Mattick. "Regulated post-transcriptional RNA cleavage diversifies the eukaryotic transcriptome." Genome Res 20: 1639-1650. (2010)

Sadlon, T. J., B. G. Wilkinson, S. Pederson, C. Y. Brown, S. Bresatz, T. Gargett, E. L. Melville, K. Peng, R. J. D'Andrea, G. G. Glonek, G. J. Goodall, H. Zola, M. F. Shannon and S. C. Barry. "Genome-wide identification of human FOXP3 target genes in natural regulatory T cells." J Immunol 185: 1071-1081. (2010)

Wang, B., M. Herman-Edelstein, P. Koh, W. Burns, K. Jandeleit-Dahm, A. Watson, M. Saleem, G. J. Goodall, S. M. Twigg, M. E. Cooper and P. Kantharidis. "E-cadherin expression is regulated by miR-192/215 by a mechanism that is independent of the profibrotic effects of transforming growth factor-beta." Diabetes 59: 1794-1802. (2010)

Wright, J. A., J. K. Richer and G. J. Goodall. "microRNAs and EMT in mammary cells and breast cancer." J Mammary Gland Biol Neoplasia 15: 213-223. (2010)

Liu B, Li J, Tsykin A, Liu L, Gaur AB and Goodall GJ. Exploring Complex miRNA-mRNA Interactions with Bayesian Networks by Splitting-Averaging Strategy BMC Bioinformatics 10: 408, 2009
Powell JA, Thomas D, Barry EF, Kok CH, McClure BJ, Tsykin A, To LB, Brown A, Lewis ID, Herbert K, Goodall GJ, Speed TP, Asou N, Jacob B, Osato M, Haylock DN, Nilsson SK, D'Andrea RJ, Lopez AF, Guthridge MA. Expression profiling of a hemopoietic cell survival transcriptome implicates osteopontin as a functional prognostic factor in AML. Blood Oct 5. [Epub ahead of print]2009.
Gibbons DL, Lin W, Creighton CJ, Rizvi ZH, Gregory PA, Goodall GJ, Thilaganathan N, Du L, Zhang Y, Pertsemlidis A, Kurie JM. Contextual extracellular cues promote tumor cell EMT and metastasis by regulating miR-200 family expression. Genes Dev. Sep 15;23(18):2140-51. 2009
Caruso M, Moore J, Goodall GJ, Thomas M, Phillis S, Tyskin A, Cheetham G, Lerda N, Takahashi H, Ruszkiewicz A. Over-expression of cathepsin E and trefoil factor 1 in sessile serrated adenomas of the colorectum identified by gene expression analysis. Virchows Arch. Mar;454(3):291-302.2009
Bracken C.P., Gregory P.A., Khew-Goodall Y., Goodall G.J. The role of microRNAs in metastasis and epithelial-mesenchymal transition. Cell Mol Life Sci. May;66(10):1682-99. 2009
Gregory PA, Bracken CP, Bert AG and Goodall GJ. MicroRNAs as regulators of epithelial –mesenchymal transition. Cell Cycle 7:3112-3118, 2008
Paterson EL, Kolesnikoff N, Gregory PA, Bert AG, Khew-Goodall Y, Goodall GJ. The microRNA-200 family regulates epithelial to mesenchymal transition. ScientificWorldJournal. Sep 21;8:901-4. 2008
Bracken CP, Gregory PA, Kolesnikoff N, Bert AG, Wang J, Shannon MF, Goodall GJ. A double-negative feedback loop between ZEB1-SIP1 and the microRNA-200 family regulates epithelial-mesenchymal transition. Cancer Res. 68: 7846-7854, 2008
Pham DH, Moretti PAB, Goodall GJ and Pitson SM (2008) Attenuation of leakiness in doxycycline-inducible expression by incorporation of 3’ AU-rich mRNA destabilizing elements. Biotechniques,Aug;45(2):155-6, 158.
Pitson SM, Goodall GJ, Guthridge MA. (2008) Science amongst the vines. Meeting on Signalling Systems. EMBO Rep. 9:425-8.
Gregory,P.A. Bert,A.G. Paterson,E.L. Barry,S.C. Tsykin,A. Farshid,G. Vadas,M.A. Khew-Goodall,Y. Goodall,G.J. The microRNA-200 family and miR-205 regulate epithelial-mesenchymal transition by targeting the E-cadherin repressors, ZEB1 and SIP1. Nature Cell Biol. 10;593-601, 2008
A.L. Brown, C.R. Wilkinson, S.R. Waterman, C.H. Kok, D.G. Salerno, S.M. Diakiw, B. Reynolds, H.S. Scott, A. Tsykin, G.F. Glonek, G.J. Goodall, P.J. Solomon, T.J. Gonda and R.J. D’Andrea. Genetic regulators of myelopoiesis and leukemic signalling identified by gene profiling and linear modelling. J. Leukocyte Biol. 80: 433-47, 2006
Bert AG, Grepin R, Vadas MA, Goodall GJ. Assessing IRES activity in the HIF-1a and other cellular 5' UTRs. RNA 12; 1074-1083, 2006.
C.N. Hahn, Z.J. Su, C.J. Drogemuller, A. Tsykin, S.R. Waterman, P.J. Brautigan, S. Yu, G. Kremmidiotis, A. Gardner, P.J. Solomon, G.J. Goodall, M.A. Vadas and J.R. Gamble. Identification Of Functionally Important Genes And Co-Ordinately Regulated Signalling Pathway Genes In Angiogenesis In Vitro. Physiol. Genomics 22; 57-69, 2005
R. T. Sladic, C. A. Lagnado, C. J. Bagley and G. J. Goodall: Human PABP Binds AU-rich RNA via RNA-Binding Domains 3 and 4. Eur. J Biochem. 271: 450-457, 2004.
L.S. Coles, M.A. Bartley, A.G. Bert, J. Hunter, S.W. Polyak, P. Diamond, M.A. Vadas and G.J. Goodall: A multi-protein complex containing cold shock domain (Y-Box) and polypyrimidine tract binding proteins forms on the vascular endothelial growth factor mRNA - potential role in mRNA stabilization. Eur. J. Biochem 271: 648-660, 2004.
Z.-J. Su, C. N. Hahn, G. J. Goodall, N. M. Reck, A. F. Leske, A. Davy, G. Kremmidiotis, M.A. Vadas and J.R. Gamble. A Vascular Cell Restricted RhoGAP, p73RhoGAP, is a Key Regulator of Angiogenesis. Proc. Natl. Acad. Sci. USA, 101; 12212-12218, 2004.
J. Zhou, M Callapina, G. J. Goodall, and B. Brüne. Functional Integrity of Nuclear Factor kB, Phosphatidylinositol 3’-Kinase, and Mitogen-Activated Protein Kinase Signaling Allows Tumor Necrosis Factor a-Evoked Bcl-2 Expression to Provoke Internal Ribosome Entry Site-Dependent Translation of Hypoxia-Inducible Factor 1a. Cancer Res.64; 9041-9048, 2004.
G.J. Goodall, L.S. Coles, M.A. Bartley and K. J. D. Lang: Post-transcriptional regulation of VEGF. In “Genetics of Angiogenesis”, J. Hoying ed. BIOS Scientific Publishers Ltd. Oxford UK, 69- 83, 2003.
R. A. Putland, T. A. Sassinis, J. S. Harvey, P. Diamond, L. S. Coles, C. Y. Brown and G. J. Goodall: RNA destabilisation by the G-CSF Stem-Loop Destabilising Element involves a single stem-loop that promotes deadenylation. Mol. Cell Biol. 22 (6); 1664-1673, 2002.
K. J. D. Lang, A. Kappel and G. J. Goodall: Hypoxia Inducible Factor-1? mRNA Contains an Internal Ribosome Entry Site that allows efficient translation during hypoxia. Mol. Biol. Cell 13;1792-1801, 2002.
L.S. Coles, P. Diamond, L. Lambrusco, J. Hunter, J. Burrows, M.A. Vadas and G.J. Goodall: A novel mechanism of repression of the VEGF promoter by single strand DNA binding cold shock domain proteins (Y-box) in normoxic fibroblasts. Nucl. Acids Res 30: 4845-4854, 2002.

Funding

National Health and Medical Research Council

"Regulation of expression of the microRNA-200 family"
GJ Goodall, MF Shannon, Y Khew-Goodall, A Ruszkiewicz
2008-2010 $550,500

NHMRC Development Grant
"Inhibition of metastasis by miR-200"
GJ Goodall, Y Khew-Goodall
2009 AU$168750 2010 AU $89750

Cancer Council of South Australia

"mRNA targets of microRNAs involved in metastasis"
2007- 2008 $77,250 per year

Research Associateship in Microarray Bioinformatics
2007- 2008 $42,588
2008- 2009 $44,078

Cancer Council SA Project Grant
"miR-200 and other microRNAs in breast cancer"
GJ Goodall, G Farshid
2009 $101,526

BioInnovation SA AIBLabs Fund

Adelaide Microarray Facility
GJ Goodall, R Richards, Z Rudzki, S Koblar, D Keefe, B Kuss, R D’Andrea
2007/08 $42,588; 2008/09 $44,078

BioInnovationSA Commercial Development Initiative
"Blocking tumour invasion and metastasis with microRNAs"
GJ Goodall
2008 AU$50,000

ARC Linkage Infrastructure Equipment Fund

"A microarray platform for gene expression analysis and genotyping in biological systems"
Prof WD Tilley; Prof JA Owens; A/Prof ML Whitelaw; Dr SA Koblar; Dr MR Beard; Dr GJ Goodall; Prof RA McKinnon; Prof D Watson
2007: $196,000

Available Student Projects

Several PhD or honours projects are available, with the general aims of examining the role of these regulated microRNAs in tumour metastasis, identifying the pathways through which they operate, and devising microRNA-based approaches to block metastasis. These include: investigation of the signalling pathways initiated by TGFβ that regulate miR-200; identifying microRNA targets; transgenic animal models (mice, zebrafish) to investigate miR-200 expression and function; microRNAs in tumour stem cells. Contact A/Prof Goodall for details.