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A/Prof Elaine Sanij

Research Unit

DNA damage & cancer therapy

Information

Head, DNA Damage and Cancer Therapy Laboratory
Victorian Cancer Agency Mid-Career Research Fellow
Email: [email protected]

Professional Experience

1999-2003      PhD, Monash Institute of Reproduction and Development (now
                       known as the Hudson Institute of Medical Research),
                       Monash University
2003-2005     Cancer Research UK Postdoctoral Fellow (Awarded Cancer
                       Research UK Fellowship), Molecular Oncology Laboratory,
                       London Research Institute, London, United Kingdom
2006-2017     Senior Postdoctoral Research Officer, Oncogenic Signalling
                       and Growth Control Program, Peter MacCallum Cancer Centre
2017-2021      Senior Research Fellow, Peter MacCallum Cancer Centre
2019               Ethical Leadership Program, Centre for Ethical Leadership,
                       Cranlana Centre for Ethical Leadership, Australia
2021               Head, DNA Damage and Cancer Therapy Laboratory, SVI

Achievements

2003- 2005      Cancer Research UK Postdoctoral Fellowship
2006                Young investigator award, the 9th Annual Australian Cell Cycle
                        Meeting
2018                Highly Commended Peter Mac Lea Medal Award, recognising
                        research excellence by emerging female research leaders
2018                Victorian Cancer Agency Sponsorship to attend a Victorian
                        Government Medical Research Trade Mission delegation to
                        Japan
2020-2024      Victorian Cancer Agency Mid-Career Research Fellowship

Research Interests

A/Prof Elaine Sanij is an experienced cancer biologist investigating innovative cancer therapeutics targeting the DNA damage response. She uses her expertise and knowledge in the cellular response to DNA damage to develop effective therapeutic approaches to target relapsed ovarian cancer and the blood cancer multiple myeloma, which currently have limited treatment options and a poor survival outcome.

Her team investigates a novel approach to cancer therapy that is currently showing promising activity in early phase clinical trials, in both blood and solid cancers. Her pre-clinical studies have shown that this therapy has real potential in treatment-resistant ovarian cancer and multiple myeloma models. Her team is also investigating new vulnerabilities that could stop ovarian cancer cells from being able to repair the DNA damage caused by chemotherapy. This has the potential to be extended to a wider range of cancers, including breast, prostate and pancreatic cancers.

Selected Publications

  1. Yan S., Xuan J., Brajanovski N., Tancock M., Madhamshettiwar P., Simpson K., Ellis S., Kang J., Cullinane C., Sheppard K. E., Hannan K. M, Hannan R. D., Sanij E. *, Pearson R. B. * and Chan K*. The RNA polymerase I transcription inhibitor CX-5461 cooperates with topoisomerase 1 inhibition by enhancing the DNA damage response in homologous recombination-proficient high-grade serous ovarian cancer. British Journal of Cancer (2021); Feb;124(3):616-627.* co-senior author
  2. Sanij E.*,#, Hannan K. M.*, Xuan J., Brajanovski N., Ahern J., Yan S., Chan K. T., Son J., Kondrashova O., Lieschke E., Wakefield M., Trigos A., Frank D., Cullinane C., Poortinga G., Khanna K., Andrew J. Deans, Mileshkin L., McArthur G. A., Soong J., Berns E., Hannan R. D., Scott C., Sheppard K. E. and Pearson R. B#. CX-5461 activates the DNA damage response and demonstrates therapeutic efficacy in high-grade serous ovarian cancer. Nature Communications (2020) May 11(1):2641. *co-first author, # co-corresponding authors *This study shows the Pol I transcription inhibitor CX-5461 is a promising therapy in ovarian cancer utilizing HGSOC-patient-derived xenographs models
  3. Kusnadi E., Trigos A. Cullinane C., Goode D., Larsson O., Devlin J., Chan K., De Souza D., McConville M., McArthur., G., Thomas G., Sanij E., Poortinga G., Hannan R., Hannan K., Kang J and Pearson R. Reprogrammed mRNA translation drives metabolic response to therapeutic targeting of the ribosome biogenesis. EMBO J (2020) Nov 2; 39(21): e105111.
  4. Son J., Hannan K. M., Poortinga G., Hein N., Cameron D., Ganley A. R., Sheppard K. E., Pearson R. B., Hannan R.D. * and Sanij E*.  rDNA chromatin activity status as a biomarker of sensitivity to the RNA polymerase I transcription inhibitor CX-5461. Frontiers in Cell Developmental Biology (2020) 2020; 8: 568. * co-senior author
  5. Xuan J., Pearson R. B. and Sanij E. CX-5461 can destabilize replication forks in PARP inhibitor-resistant models of ovarian cancer. Molecular & Cellular Oncology (2020) July 7 (6): Author’s Views.
  6. Khot A., Brajanovski N., Cameron D.P., Hein N., Maclachlan K.H., Sanij E., Lim J., Soong J., Link E., Blombery P., Thompson ER., Fellowes a., Sheppard KE., McArthur GA., Pearson RB., Hannan RD., Porrtinga G and Harrison SJ. First-in-Human RNA Polymerase I Transcription Inhibitor CX-5461 in Patients with Advanced Hematological Cancers: Results of a Phase I Dose Escalation Study. Cancer Discovery (2019) 9 (8), 1036-1049. 
    Significance: Critical paper describing the first-in-human clinical trial of the first-in-class Pol I inhibitor CX-5461, demonstrating CX-5461 has single-agent anti-tumour activity against advanced hematological cancers.
  7. Udugama M.*, Sanij E.*, Voon H. P., Son J., Hii L., Henson J., Chan F., Chang F. T. M., Liu Y., Pearson R. B., Kalitsis P., Mann J. R., Collas P., Hannan R. D.  and Wong L. H. Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers. Proceedings of the National Academy of Sciences (PNAS) (2018) May 1;115(18):4737-4742. co-first author.
    Significance: In this paper, we demonstrated a role for alpha thalassemia/mental retardation X-linked (ATRX) in mediating rRNA gene loci stability. ATRX is mutated in various cancers including brain cancers, pancreatic neuroendocrine tumours and osteosarcoma. This paper demonstrates evidence that ATRX-mutated cancers exhibit rRNA gene loci instability providing therapeutic potential of targeting Pol I transcription inhibition by CX-5461 in a wide range of ATRX-mutated cancers.
  8. Yan S., Frank D., Son J., Hannan M.,
 Hannan D., Chan K., Pearson R and Sanij E. The potential of targeting ribosome biogenesis in high-grade serous ovarian cancer. International Journal Molecular Science (2017):18(1), 210; doi:10.3390.
  9. Hung S., Lesmana A., Peck A., Lee R, Tchoubrieva E., Hannan K., Lin J., Sheppard K., Jastrzebski K., Quinn L., Rothblum L, Pearson R, Hannan R* and Sanij E*. Cell cycle and growth stimuli regulate different steps of RNA polymerase I transcription. Genes (2017) 612:36-48. *co-senior author
    Significance: This paper identified Pol I transcription elongation as rate limiting for rRNA synthesis and proposed dual targeting of Pol I transcription initiation and elongation as an effective therapeutic approach in Pol I cancer therapy.
  10. Quin J., Chan T.K, Devlin J.R, Cameron D.P, Diesch J, Cullinane C, Ahern J, Khot A, Hein N, George A.J, Hannan K.M, Poortinga G, Sheppard E, Khanna K, Johnstone R.W, Drygin D, McArthur G.A, Pearson R.B, Sanij E*. Hannan R.D*. Inhibition of RNA Polymerase I transcription initiation activates non-canonical ATM/ATR Signalling. Oncotarget (2016) 7(31): 49800-49818. *co-senior author
    Significance: In this paper, we showed that CX-5461 activates DNA damage signalling pathways within the nucleoli and sensitizes cells to DNA damaging agents. We demonstrated that the combination of CX-5461 and a drug targeting ATM/ATR signalling improved therapeutic efficacy in vivo thus extending the utility of both classes of drugs.
  11. Sanij E.*, Diesch J., Lesmana A., Poortinga G., Hein N., Lidgerwood G., Cameron D.P., Ellul J., Goodall G.J., Wong L.H., Dhillon A.S., Hamdane N., Rothblum L.I., Pearson R.B., Haviv. I., Moss T. and Hannan, R.D*. A novel role for the Pol I transcription factor UBTF in maintaining genome stability through the regulation of highly transcribed Pol II genes. Genome Research (2015); 5(2):201-212. *Corresponding authors
    Significance: In this paper, we reported a novel role the Pol I-transcription factor UBTF in regulating the expression of highly transcribed Pol II genes critical for chromatin packaging and DNA repair. The coordinated regulation of these processes emphasizes the therapeutic opportunities of targeting Pol I transcription for cancer therapy.
  12. Diesch J., Hannan R. and Sanij E. Perturbations at the ribosomal genes loci are at the centre of cellular dysfunction and human disease. Cell & Bioscience (2014); 4:43.
  13. Hein N., Hannan K.M., George A.J., Sanij E.*, Hannan R*. The Nucleolus: an emerging target for cancer therapy. Trends In Molecular Medicine (2013); 19(11):643-54. (*co-senior)
    Significance: This was an invited review following the publication of Bywater et al., Cancer Cell paper in 2012. The review highlighted the potential of targeting Pol I transcription as an exciting novel target for cancer therapy.
  14. Bywater M., Poortinga G., Sanij E., Hein N., Peck a., Cullinane C., Wall M., Cluse L., Drygin D., Anderes K., Huser N., Proffitt C., Bliesath J., Haddach M., Schwaebe M., Ryckman D.M. Rice W.G., Lowe S.W., Johnstone R.W., Pearson R.B., McArthur G.A., Hannan R. Inhibition of RNA Polymerase I as a therapeutic strategy to promote cancer-specific activation of p53. Cancer Cell (2012); 22(1):51-65.
    Significance: Critical and high-profile paper demonstrating that dysregulated Pol I transcription can be targeted in vivo to selectively kill cancer cells. Resulted in the initiation of clinical trial of CX-5461 targeting patients with haematological malignancies at Peter Mac.
  15. Sanij E., Poortinga G., Sharkey K., Hung S., Holloway T., Quin J., Robb E., Wong L., Thomas W., Stefanovsky V., Moss T., Rothblum L., McArthur G., Pearson R. and Hannan R. UBF levels determine the number of active ribosomal RNA genes in mammals. Journal of Cellular Biology (2008);183: 1259-1274. [IF: 8.89]
    Significance: This paper demonstrated that UBTF determines a dynamic transition between  active and inactive ribosomal RNA gene states. This study is fundamental to our current understanding of how CX-5461 induces a defect in ribosomal RNA gene chromatin that activates DNA damage signalling, which can be targeted to improve therapeutic efficacy. This article was highlighted in Science magazine as the editor’s choice of recent literature highlights in molecular biology, Pickersgill, Science (2008) 323, 5913, pp.439.