Dr Michelle Brown

Associate Lecturer

School of Biomedical Sciences and Pharmacy (Medical Genetics)

Career Summary

Biography

I produced 3 peer-reviewed papers during my postgraduate term. One of them, "BRIP1PALB2, and RAD51C mutation analysis reveals their relative importance as genetic susceptibility factors for breast cancer" was one of the early publications to show that PALB2 germline mutations are involved in the genetic predisposition to famlial breast cancer, and has ben cited 35 times to date, including by other high-impact publications.

The most notable achievements in my academic career was being awarded the HMRI PhD Student Conference Award, the HMRI Research Higher Degree Support Grant in Medical Innovation and receiving the Faculty Medal from the Faculty of Health for graduating with Honours Class I with excellent undergraduate results. I am also keen on community involvement, as evident by my participation in various HMRI initiatives. I believe in the importance of creating awareness in the general public about the research being conducted at HMRI. 

Research Expertise

One of my research strengths is in gene sequencing, from primer design to sequencing analysis. I gained this knowledge during my secondment to the Division of Molecular Genetics at Hunter Area Pathology Service (HAPS). I am currently assisting two undergraduate students with their placement project involving sequencing of several genes involved in cancer.

Teaching Expertise
I have previously been a tutor for the Bioinformatics and Functional Genomics (HUBS 2409) course at the University of Newcastle. 

Collaborations
I frequently collaborate with the Molecular Genetics laboratory at Hunter Area Pathology Service, Newcastle.


Qualifications

  • Doctor of Philosophy, University of Newcastle
  • Bachelor of Biomedical Sciences, University of Newcastle
  • Bachelor of Biomedical Sciences (Hons), University of Newcastle

Keywords

  • Breast Cancer
  • Clinical Genetics
  • Genetics

Languages

  • Malay (Fluent)

Fields of Research

Code Description Percentage
110311 Medical Genetics (excl. Cancer Genetics) 70
111203 Cancer Genetics 10
060499 Genetics not elsewhere classified 20

Professional Experience

Academic appointment

Dates Title Organisation / Department
1/10/2012 -  Research assistant University of Newcastle
Centre for Information-Based Medicine
Australia
1/09/2009 - 1/09/2010 Tutor University of Newcastle
School of Biomedical Sciences
Australia
1/08/2008 -  Research assistant University of Newcastle
Australia

Professional appointment

Dates Title Organisation / Department
1/11/2008 - 1/02/2009 Hospital scientist Hunter Area Pathology Service
Division of Genetics
Australia
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Publications

For publications that are currently unpublished or in-press, details are shown in italics.


Journal article (14 outputs)

Year Citation Altmetrics Link
2016 Thompson ER, Rowley SM, Li N, McInerny S, Devereux L, Wong-Brown MW, et al., 'Panel testing for familial breast cancer: Calibrating the tension between research and clinical care', Journal of Clinical Oncology, 34 1455-1459 (2016)

© 2016 by American Society of Clinical Oncology.Purpose Gene panel sequencing is revolutionizing germline risk assessment for hereditary breast cancer. Despite scant evidence sup... [more]

© 2016 by American Society of Clinical Oncology.Purpose Gene panel sequencing is revolutionizing germline risk assessment for hereditary breast cancer. Despite scant evidence supporting the role of many of these genes in breast cancer predisposition, results are often reported to families as the definitive explanation for their family history. We assessed the frequency of mutations in 18 genes included in hereditary breast cancer panels among index cases from families with breast cancer and matched population controls. Patients and Methods Cases (n= 2,000) were predominantly breast cancer-affected women referredto specialized Familial Cancer Centers on the basis of a strong family history of breast cancer and BRCA1 and BRCA2 wild type. Controls (n = 1,997) were cancer-free women from the LifePool study. Sequencing data were filtered for known pathogenic or novel loss-of-function mutations. Results Excluding 19 mutations identified in BRCA1 and BRCA2 among the cases and controls, a total of 78 cases (3.9%) and 33 controls (1.6%) were found to carry potentially actionable mutations. A significant excess of mutations was only observed for PALB2 (26 cases, four controls) and TP53 (five cases, zero controls), whereas no mutations were identified in STK11. Among the remaining genes, loss-of function mutations were rare, with similar frequency between cases and controls. Conclusion The frequency ofmutations in most breast cancer panel genes among individuals selected for possible hereditary breast cancer is low and, in many cases, similar or even lower than that observed among cancer-free population controls. Although multigene panels can significantly aid in cancer risk management and expedite clinical translation of new genes, they equally have the potential to provide clinical misinformation and harm at the individual level if the data are not interpreted cautiously.

DOI 10.1200/JCO.2015.63.7454
Citations Scopus - 1
Co-authors Michelle Wong-Brown, Rodney Scott
2016 Wong-Brown M, McPhillips M, Gleeson M, Spigelman AD, Meldrum CJ, Dooley S, Scott RJ, 'When is a mutation not a mutation: The case of the c.594-2A\C splice variant in a woman harbouring another BRCA1 mutation in trans', Hereditary Cancer in Clinical Practice, 14 (2016)

© 2016 Wong-Brown et al.Since the identification of BRCA1 there has only ever been described two bi-allelic mutation carriers, one of whom was subsequently shown to be a mono-all... [more]

© 2016 Wong-Brown et al.Since the identification of BRCA1 there has only ever been described two bi-allelic mutation carriers, one of whom was subsequently shown to be a mono-allelic carrier. The second patient diagnosed with two BRCA1 mutations appears to be accurate but there remain some questions about the missense variant identified in that patient. In this report we have identified a woman who is a bi-allelic mutation carrier of BRCA1 and provide an explanation as to why this patient has a phenotype very similar to that of any mono-allelic mutation carrier. The splice variant identified in this patient appears to be associated with the up-regulation of a BRCA1 splice variant that rescues the lethality of being a double mutant. The consequences of the findings of this report may have implications for mutation interpretation and that could serve as a model for not only BRCA1 but also for other autosomal dominant disorders that are considered as being embryonically lethal.

DOI 10.1186/s13053-015-0045-y
Co-authors Rodney Scott, Michelle Wong-Brown
2016 Easton DF, Lesueur F, Decker B, Michailidou K, Li J, Allen J, et al., 'No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.', J Med Genet, 53 298-309 (2016)
DOI 10.1136/jmedgenet-2015-103529
Citations Scopus - 1
Co-authors Michelle Wong-Brown, Rodney Scott
2016 Morten BC, Wong-Brown MW, Scott RJ, Avery-Kiejda KA, 'The presence of the intron 3 16 bp duplication polymorphism of p53 (rs17878362) in breast cancer is associated with a low ¿40p53:p53 ratio and better outcome', Carcinogenesis, 37 81-86 (2016)

© The Author 2015. Published by Oxford University Press. All rights reserved.Breast cancer is the most common female cancer, but it has relatively low rates of p53 mutations, sug... [more]

© The Author 2015. Published by Oxford University Press. All rights reserved.Breast cancer is the most common female cancer, but it has relatively low rates of p53 mutations, suggesting other mechanisms are responsible for p53 inactivation. We have shown that the p53 isoform, ¿40p53, is highly expressed in breast cancer, where it may contribute to p53 inactivation. ¿40p53 can be produced by alternative splicing of p53 in intron 2 and this is regulated by the formation of G-quadruplex structures in p53 intron 3, from which the nucleotides forming these structures overlap with a common polymorphism, rs17878362. rs17878362 alters p53 splicing to decrease fully spliced p53 messenger RNA (mRNA) in vitro following ionizing radiation and this in turn alters ¿40p53:p53. Hence, the presence of rs17878362 may be important in regulating ¿40p53:p53 in breast cancer. This study aimed to determine if rs17878362 was associated with altered ¿40p53 and p53 expression and outcome in breast cancer. We sequenced p53 in breast tumours from 139 patients and compared this with ¿40p53 and p53 mRNA expression. We found that the ratio of ¿40p53:p53 was significantly lower in tumours homozygous for the polymorphic A2 allele compared with those who were wild-type (A1/A1). Furthermore, there was a lower proportion of breast cancers carrying the A2 allele from patients who subsequently developed metastasis compared with those that did not. Finally, we show that patients whose tumours carried the polymorphic A2 allele had significantly better disease-free survival. These results show that rs17878362 is associated with a low ¿40p53:p53 ratio in breast cancer and that this is associated with better outcome.

DOI 10.1093/carcin/bgv164
Co-authors Kelly Kiejda, Rodney Scott, Michelle Wong-Brown
2015 Thompson ER, Gorringe KL, Rowley SM, Wong-Brown MW, McInerny S, Li N, et al., 'Prevalence of PALB2 mutations in Australian familial breast cancer cases and controls', BREAST CANCER RESEARCH, 17 (2015) [C1]
DOI 10.1186/s13058-015-0627-7
Citations Scopus - 1
Co-authors Rodney Scott, Michelle Wong-Brown
2015 Wong-Brown MW, Meldrum CJ, Carpenter JE, Clarke CL, Narod SA, Jakubowska A, et al., 'Prevalence of BRCA1 and BRCA2 germline mutations in patients with triple-negative breast cancer', Breast Cancer Research and Treatment, 150 71-80 (2015) [C1]

© 2015, Springer Science+Business Media New York.Triple-negative breast cancers¿(TNBC) lack expression of oestrogen, progesterone and HER2 receptors. The gene expression profile... [more]

© 2015, Springer Science+Business Media New York.Triple-negative breast cancers¿(TNBC) lack expression of oestrogen, progesterone and HER2 receptors. The gene expression profiles of TNBCs are similar to those of breast tumours in women with BRCA1 mutations. Reports to date indicate that up to 20¿% of TNBC patients harbour germline BRCA mutations; however, the prevalence of BRCA mutations in TNBC patients varies widely between countries and from study to study. We studied 774 women with triple-negative breast cancer, diagnosed on average at age 58.0¿years. Samples of genomic DNA were provided by the Australian Breast Cancer Tissue Bank (ABCTB) (439 patients) and by the Department of Genetics and Pathology of the Pomeranian Medical University (335 patients). The entire coding regions and the exon¿intron boundaries of BRCA1 and BRCA2 were amplified and sequenced by next-generation sequencing. We identified a BRCA1 or BRCA2 mutation in 74 of 774 (9.6¿%) triple-negative patients. The mutation prevalence was 9.3¿% in Australia and was 9.9¿% in Poland. In both countries, the mean age of diagnoses of BRCA1 mutation carriers was significantly lower than that of non-carriers, while the age of onset of BRCA2 mutation carriers was similar to that of non-carriers. In the Australian cohort, 59¿% of the mutation-positive patients did not have a family history of breast or ovarian cancer, and would not have qualified for genetic testing. The triple-negative phenotype should be added as a criterion to genetic screening guidelines.

DOI 10.1007/s10549-015-3293-7
Citations Scopus - 11
Co-authors Rodney Scott, Michelle Wong-Brown
2015 Mathe A, Wong-Brown M, Morten B, Forbes JF, Braye SG, Avery-Kiejda KA, Scott RJ, 'Novel genes associated with lymph node metastasis in triple negative breast cancer', Scientific Reports, 5 (2015) [C1]

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and no targeted treatments. TNBC patients are more likely to develop met... [more]

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with the worst prognosis and no targeted treatments. TNBC patients are more likely to develop metastases and relapse than patients with other breast cancer subtypes. We aimed to identify TNBC-specific genes and genes associated with lymph node metastasis, one of the first signs of metastatic spread. A total of 33 TNBCs were used; 17 of which had matched normal adjacent tissues available, and 15 with matched lymph node metastases. Gene expression microarray analysis was used to reveal genes that were differentially expressed between these groups. We identified and validated 66 genes that are significantly altered when comparing tumours to normal adjacent samples. Further, we identified 83 genes that are associated with lymph node metastasis and correlated these with miRNA-expression. Pathway analysis revealed their involvement in DNA repair, recombination and cell death, chromosomal instability and other known cancer-related pathways. Finally, four genes were identified that were specific for TNBC, of which one was associated with overall survival. This study has identified novel genes involved in LN metastases in TNBC and genes that are TNBC specific that may be used as treatment targets or prognostic indicators in the future.

DOI 10.1038/srep15832
Co-authors Rodney Scott, John Forbes, Michelle Wong-Brown, Kelly Kiejda
2015 Thompson ER, Gorringe KL, Rowley SM, Li N, McInerny S, Wong-Brown MW, et al., 'Reevaluation of the BRCA2 truncating allele c.9976A > T (p.Lys3326Ter) in a familial breast cancer context', SCIENTIFIC REPORTS, 5 (2015) [C1]
DOI 10.1038/srep14800
Co-authors Michelle Wong-Brown, Rodney Scott
2014 Wong-Brown MW, Avery-Kiejda KA, Bowden NA, Scott RJ, 'Low prevalence of germline PALB2 mutations in Australian triple-negative breast cancer', International Journal of Cancer, 134 301-305 (2014) [C1]

Triple-negative breast cancer (TNBC) is a tumour classification that is defined by oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 receptor ... [more]

Triple-negative breast cancer (TNBC) is a tumour classification that is defined by oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 receptor negativity. TNBCs share a similar gene expression profile to BRCA-mutated tumours, have been shown to carry a high proportion of BRCA mutations and have a more adverse prognosis compared to other types of breast tumours. PALB2 has been shown to be a moderate-penetrance breast cancer susceptibility gene and is involved in the same DNA damage repair pathway as BRCA1 and BRCA2; this raises the possibility that germline PALB2 mutations may be involved in the pathogenesis of TNBCs. In our study, we sequenced the coding regions of PALB2 (including intron/exon boundaries) in genomic DNA from 347 patients diagnosed with TNBC to determine the prevalence of deleterious mutations in this population. Two novel truncating mutations (c.758dup and c.2390del) and one previously detected truncating mutation (c.3113+5G>C) were found. In addition, five variants predicted to be protein-affecting were also identified. Our study shows that the prevalence of PALB2 germline mutations in individuals with TNBC is ~1%, similar to the prevalence of PALB2 germline mutation of 1% in familial non-BRCA1/2 breast cancer cohorts. © 2013 UICC.

DOI 10.1002/ijc.28361
Citations Scopus - 4Web of Science - 3
Co-authors Kelly Kiejda, Michelle Wong-Brown, Rodney Scott, Nikola Bowden
2014 Avery-Kiejda KA, Morten B, Wong-Brown MW, Mathe A, Scott RJ, 'The relative mRNA expression of p53 isoforms in breast cancer is associated with clinical features and outcome.', Carcinogenesis, 35 586-596 (2014) [C1]
DOI 10.1093/carcin/bgt411
Citations Scopus - 9Web of Science - 4
Co-authors Rodney Scott, Kelly Kiejda, Michelle Wong-Brown
2013 Wong-Brown MW, McPhillips ML, Hipwell M, Pecenpetelovska G, Dooley S, Meldrum C, Scott RJ, 'cDNA analysis of the BRCA1 unclassified variant c.5194-12G > A', CLINICAL GENETICS, 84 505-506 (2013) [C3]
DOI 10.1111/cge.12052
Co-authors Michelle Wong-Brown, Rodney Scott
2011 Zacharin M, Bajpai A, Chow CW, Catto-Smith A, Stratakis C, Wong-Brown M, Scott R, 'Gastrointestinal polyps in McCune Albright syndrome', Journal of Medical Genetics, 48 458-461 (2011) [C1]
DOI 10.1136/jmg.2010.086330
Citations Scopus - 8Web of Science - 5
Co-authors Rodney Scott, Michelle Wong-Brown
2011 Kiejda KA, Wong-Brown M, Scott R, 'Genetic markers in breast cancer - How far have we come from BRCA1?', Asia-Pacific Journal of Molecular Medicine, 1 1-15 (2011) [C1]
Co-authors Michelle Wong-Brown, Rodney Scott, Kelly Kiejda
2011 Wong-Brown M, Nordfors C, Mossman D, Pecenpetelovska G, Kiejda KA, Talseth-Palmer B, et al., 'BRIP1, PALB2, and RAD51C mutation analysis reveals their relative importance as genetic susceptibility factors for breast cancer', Breast Cancer Research and Treatment, 127 853-859 (2011) [C1]
DOI 10.1007/s10549-011-1443-0
Citations Scopus - 57Web of Science - 40
Co-authors Bente Talseth-Palmer, Michelle Wong-Brown, Nikola Bowden, Rodney Scott, Kelly Kiejda
Show 11 more journal articles

Conference (17 outputs)

Year Citation Altmetrics Link
2015 Morten B, Wong-Brown M, Scott R, Avery-Kiejda K, 'ASSOCIATION OF THE POLYMORPHIC INTRON 3 16 BP DUPLICATION IN TP53 (RS17878362) WITH A LOW Delta 40P53:P53 RATIO AND BETTER OUTCOME IN BREAST CANCER', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2015) [E3]
Co-authors Michelle Wong-Brown, Rodney Scott, Kelly Kiejda
2014 Morten B, Campbell HG, Brown MW, Mathe A, Braithwaite AW, Scott RJ, Kiejda KA, '¿40p53 regulation of estrogen responsiveness in breast cancer.', 16th International p53 Workshop Proceedings (2014) [E3]
Co-authors Michelle Wong-Brown, Rodney Scott, Kelly Kiejda
2014 Avery-Kiejda KA, Morten B, Wong-Brown MW, Mathe A, Scott RJ, 'The relationship between p53 isoforms and prognosis in breast cancer.', The Australian Society for Medical Research (ASMR) Satellite Scientific Meeting Programme (2014) [E3]
Co-authors Michelle Wong-Brown, Kelly Kiejda, Rodney Scott
2014 Mathe A, Avery-Kiejda KA, Wong-Brown M, Morten B, Forbes JF, Braye SG, Scott RJ, 'IDENTIFICATION OF NOVEL TRANSCRIPTS SPECIFIC TO TRIPLE NEGATIVE BREAST CANCER THAT ARE ASSOCIATED WITH LYMPH NODE METASTASIS', ASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY (2014) [E3]
DOI 10.1111/ajco.12335
Co-authors Michelle Wong-Brown, Kelly Kiejda, Rodney Scott, John Forbes
2014 Mathe A, Avery-Kiejda KA, Wong-Brown M, Forbes JF, Braye SG, Scott RJ, 'Eight microRNAs as biomarkers for metastatic spread in triple negative breast cancer', EUROPEAN JOURNAL OF CANCER (2014) [E3]
Co-authors Rodney Scott, Michelle Wong-Brown, John Forbes, Kelly Kiejda
2014 Wong-Brown M, Scott RJ, 'Low prevalence of germline PALB2 mutations in Australian triple-negative breast cancer', Abstract booklet (2014) [E3]
Co-authors Michelle Wong-Brown, Rodney Scott
2013 Mathe A, Avery-Kiejda KA, Wong-Brown MW, Forbes JF, Braye SG, Scott RJ, 'Target gene identification of microRNAs associated with lymph node metastases in triple negative breast cancer.', 25th Lorne Cancer Conference Proceedings (2013) [E3]
Co-authors Kelly Kiejda, Michelle Wong-Brown, John Forbes, Rodney Scott
2013 Mathe A, Avery-Kiejda KA, Wong-Brown M, Forbes JF, Braye SG, Scott RJ, 'Integration of microRNA and gene expression profiling in triple negative breast cancer to identify possible biomarkers for metastases.', Breakthrough Breast Cancer TNBC Conference Proceedings (2013) [E3]
Co-authors Rodney Scott, Kelly Kiejda, Michelle Wong-Brown, John Forbes
2013 Wong-Brown M, Li S, Wilkins M, Avery-Kiejda KA, Bowden N, Scott R, 'Targeted resequencing of BRCA1 and BRCA2 in familial breast cancer.', Kathleen Cunningham Foundation Consortium for Research into Familial Aspects of Cancer 2013 Research and Practice Proceedings (2013) [E3]
Co-authors Nikola Bowden, Kelly Kiejda, Michelle Wong-Brown, Rodney Scott
2013 Wong-Brown M, Avery-Kiejda K, Bowden N, Scott R, 'Prevalence of BRCA1 and BRCA2 germline mutations in triple-negative breast cancer', Programme (2013) [E3]
Citations Web of Science - 3
Co-authors Nikola Bowden, Rodney Scott, Michelle Wong-Brown, Kelly Kiejda
2013 Mathe A, Wong-Brown M, Forbes JF, Braye SG, Scott RJ, Avery-Kiejda KA, 'Identification of biomarkers for metastatic spread in triple negative breast cancer.', Translational Cancer Research Conference Abstract booklet (2013) [E3]
Co-authors John Forbes, Rodney Scott, Kelly Kiejda, Michelle Wong-Brown
2012 Wong-Brown M, Li S, Wilkins M, Kiejda KA, Bowden NA, Scott R, 'Exploratory targeted resequencing of BRCA1 and BRCA2 in inherited breast cancer', Programme. kConFab Familial Aspects of Cancer: Research & Practice 2012 (2012) [E3]
Co-authors Michelle Wong-Brown, Rodney Scott, Nikola Bowden, Kelly Kiejda
2012 Gleeson M, Spigelman AD, Meldrum CJ, Dooley S, Wong-Brown M, Young B, et al., 'A case of two mutations in trans in a women diagnosed with breast cancer at the age of 3+0 years', Programme. kConFab Familial Aspects of Cancer: Research & Practice 2012 (2012) [E3]
Co-authors Rodney Scott, Michelle Wong-Brown
2012 Wong-Brown M, Li S, Wilkins M, Kiejda KA, Bowden NA, Scott R, 'Targeted resequencing of BRCA1 and BRCA2 in inherited breast cancer', Cancer Research (2012) [E3]
Co-authors Kelly Kiejda, Michelle Wong-Brown, Rodney Scott, Nikola Bowden
2011 Wong-Brown M, Scott R, Hibberd A, Trevillian PR, Clark D, Meldrum C, 'Measurement of Foxp3 gene expression in renal transplant recipients', Immunology and Cell Biology (2011) [E3]
Co-authors Rodney Scott, Michelle Wong-Brown
2010 Wong-Brown M, Bowden NA, Kiejda KA, Scott R, 'BRIP1 and PALB2 mutation detection in Hunter-New England familial breast cancer cohort', 27th HUGO-IABCR Congress 2010. Genomics, Biology and Breast Cancer Treatment. Programme & Abstract Book (2010) [E3]
Co-authors Michelle Wong-Brown, Rodney Scott, Nikola Bowden, Kelly Kiejda
2010 Wong-Brown M, Bowden NA, Forbes JF, Braye SG, Scott R, 'Microsatellite instability (I) in breast tumours', Sydney Cancer Conference 2010. Profiling Risk, Personalising Treatment and Predicting Outcomes. Conference Program and Abstract Book (2010) [E3]
Co-authors Michelle Wong-Brown, Rodney Scott, John Forbes, Nikola Bowden
Show 14 more conferences
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Grants and Funding

Summary

Number of grants 2
Total funding $36,000

Click on a grant title below to expand the full details for that specific grant.


20142 grants / $36,000

Targeted next-generation sequencing of potential breast cancer susceptibility genes$30,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Michelle Brown, Professor Rodney Scott
Scheme Bridging Grant
Role Lead
Funding Start 2014
Funding Finish 2014
GNo G1301293
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y

Karen Brown Breast Cancer Research Travel Grant$6,000

Funding body: Hunter Medical Research Institute

Funding body Hunter Medical Research Institute
Project Team Doctor Michelle Brown
Scheme Karen Brown Breast Cancer Research Travel Grant
Role Lead
Funding Start 2014
Funding Finish 2014
GNo G1401509
Type Of Funding Grant - Aust Non Government
Category 3AFG
UON Y
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Dr Michelle Brown

Position

Associate Lecturer
Centre for Information-Based Medicine
School of Biomedical Sciences and Pharmacy
Faculty of Health and Medicine

Focus area

Medical Genetics

Contact Details

Email michelle.wong-brown@newcastle.edu.au
Phone (02) 4042 0321
Fax (02) 4042 0031

Office

Room HMRI Level 3 West
Building Hunter Medical Research Institute
Location Hunter Medical Research Institute

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