Dr Megan Chircop

Lecturer
Medicine, Children's Medical Research Institute

Telephone +61 2 9687 2800
Fax +61 2 9687 2120

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Biographical details

I am a molecular and cellular biologist with research interests focusing on the molecular mechanisms of mitosis and cancer. I obtained my BSc Honours degree in molecular biology/biochemistry at Macquarie University in 1999. I have a PhD in cancer research at the University of Sydney in 2002. My first post-doc position was at the Queensland Institute of Medical Research (QIMR) in Brisbane where I worked for 3 years. I then moved to the Children's Medical Research Institute (CMRI) in Sydney in 2006 as an NH&MRC Peter Doherty Fellow. Since 2008, I am an NHMRC CDA Fellow and currently head the CellCycle Unit at the CMRI consisting of 10 members. I am a leading scientist in my discipline and show scientific leadership.

Research interests

The major focus of my laboratory is to precisely define the mechanisms regulating mitotic cell division. Understanding the molecular regulation of mitosis will allow us to gain insight into cancer biology mechanisms. Despite the identification of many mitotic proteins, the molecular mechanisms driving mitotic progression and how these proteins cooperatively function to complete mitosis in mammalian cells is not fully understood. Cell division errors increase the oncogenic potential of a cell. Thus understanding this basic biological process underpins our understanding of cancer biology mechanisms, which can lead to the identification of druggable targets to treat this disease. My discoveries to date in this field have enabled me to develop a well respected national and international reputation in this field. This provides me with a strong foundation that I aim to continue developing in the future. My research will continue to expand in two areas: 1) Basic research: molecular mechanisms of mitosis 2) Translational biology: drug discovery of new anti-mitotic compounds for cancer treatment.

Teaching and supervision

After only 8 post-doc years, I have contributed substantially to teaching, training and mentoring young scientists to an unusually high level. In the past 7 years at the CMRI my team has consistent of 10-12 members and currently involves 3RAs , 4PhDs, 3postdocs whereby I am directly involved in training and mentoring them all. Overall, I have supervised 11 students (8 PhD and 3 Honours). All three honours students completed with first class, 1 has completed a PhD (2011), another has established a career in the Governor General's Office of Australia and the third is about to commence a PhD in my lab (2013). All of my PhD students have received prestigious awards including external scholarships such as the Australian Postgraduate Award (APA). Four PhD students have completed their PhDs and three of these have postdoc positions in prestigious international labs including Beatson's Institute (Scotland), Max Plank Gesellschaft Institute (Germany) and Queens University Belfast (Ireland) and the other is an Application Specialist/Territory Manager at Promega. I anticipate that my postgraduate supervisory commitment will continue at 3-4 students per year. Since 2009, I have been an active member of the CMRI PhD review committee that assesses the annual progress of research students within CMRI. I have also mentored 5 post-docs in the past 5 years to aid in advancing their scientific careers. One of these post-docs (Dr Rose Boutros) was an NHMRC Peter Doherty Fellow (2008-2011) and has received NHMRC project, Cure Cancer Australia and Ramaciotti grant funding for her own projects.

Selected grants

2014

  • WAVE 20/50 Bioreactor and C5 Cell Disruptor; Chircop (nee Fabbro) M, Kizana E, Robinson P, Diefenbach R, Bryan T, Gottlieb D, Micklethwaite K, Alexander I; National Health and Medical Research Council (NHMRC)/Equipment Grants.
  • Defining the cellular determinants that drive dynamin inhibitor induced cell death and in vivo efficacy against glioblastoma; Chircop (nee Fabbro) M, McCluskey A, Jones N, Sakoff J, D'Abaco G; Cancer Council New South Wales/Research Project Grants.

2013

  • Role of endocytic mechanisms in mammalian cytokinesis; Chircop (nee Fabbro) M; Australian Research Council (ARC)/Discovery Projects (DP).
  • Fluidigm BioMark HD - HX; Alexander I, Jamieson R, Chircop (nee Fabbro) M, Byrne J, Catchpoole D, Reddel R, Tam P, Robinson P, Bryan T, Diefenbach R; National Health and Medical Research Council (NHMRC)/Equipment Grants.

2012

  • The role of clathrin in the spindle assembly checkpoint and as an anti-cancer target; Chircop (nee Fabbro) M, Robinson P, McCluskey A, Sakoff J; National Health and Medical Research Council (NHMRC)/Project Grants.

2010

  • Dynamin as a new drug target for the treatment of glioblastoma; Chircop (nee Fabbro) M, Sakoff J, McCluskey A, Jones N; Cancer Council New South Wales/Research Project Grants.

2009

  • Understanding the molecular requirements of the endocytic machinery for mammalian cytokinesis; Chircop (nee Fabbro) M; DVC Research/Bridging Support Grant.
  • Dynamin inhibitors as new anti-cancer drugs; Chircop (nee Fabbro) M, Sakoff J; Cancer Council New South Wales/Research Project Grants.

2007

  • Confocal microscope for cancer research in the northern hub; Robinson P, Gunning P, Hardeman E, Henderson B, Bendall L, Chircop (nee Fabbro) M; Cancer Institute New South Wales/Research Grant.

Selected publications

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Book Chapters

  • Chircop (nee Fabbro), M. (2012). Protein Phosphatases Drive Mitotic Exit. In Gabriela Da Silva Xavier (Eds.), Protein Kinases, (pp. 215-228). Rijeka: InTech Publishers.

Journals

  • McCluskey, A., Daniel, J., Hadzic, G., Chau, N., Clayton, E., Mariana, A., Whiting, A., Gorgani, N., Lloyd, J., Quan, A., Moshkanbaryans, L., Krishnan, S., Perera, S., Chircop (nee Fabbro), M., Robinson, P., et al (2013). Building a better dynasore: the dyngo compounds potently inhibit dynamin and endocytosis. Traffic (Malden), 14(12), 1272-1289. [More Information]
  • Boutros, R., Mondesert, O., Lorenzo, C., Astuti, P., McArthur, G., Chircop (nee Fabbro), M., Ducommun, B., Gabrielli, B. (2013). CDC25B Overexpression Stabilises Centrin 2 and Promotes the Formation of Excess Centriolar Foci. PLoS One, 8(7), 1-13. [More Information]
  • Gordon, C., Venn-Brown, B., Robertson, M., Young, K., Chau, N., Mariana, A., Whiting, A., Chircop (nee Fabbro), M., Robinson, P., McCluskey, A. (2013). Development of second-generation indole-based dynamin GTPase inhibitors. Journal of Medicinal Chemistry, 56(1), 46-59. [More Information]
  • Smith, C., Haucke, V., McCluskey, A., Robinson, P., Chircop (nee Fabbro), M. (2013). Inhibition of clathrin by pitstop 2 activates the spindle assembly checkpoint and induces cell death in dividing HeLa cancer cells. Molecular Cancer, 12(4), 1-15. [More Information]
  • McGeachie, A., Odell, L., Quan, A., Daniel, J., Chau, N., Hill, T., Gorgani, N., Keating, D., Cousin, M., van Dam, E., Whiting, A., Perera, S., Novelle, A., Chircop (nee Fabbro), M., Robinson, P., et al (2013). Pyrimidyn Compounds: Dual-Action Small Molecule Pyrimidine-Based Dynamin Inhibitors. ACS Chemical Biology, 8(7), 1507-1518. [More Information]
  • Ma, M., Robinson, P., Chircop (nee Fabbro), M. (2013). Sorting Nexin 9 Recruits Clathrin Heavy Chain to the Mitotic Spindle for Chromosome Alignment and Segregation. PLoS One, 8(7), 1-11. [More Information]
  • Smith, C., Chircop (nee Fabbro), M. (2012). Clathrin-Mediated Endocytic Proteins are Involved in Regulating Mitotic Progression and Completion. Traffic (Malden), 13(12), 1628-1641. [More Information]
  • Ma, M., Chircop (nee Fabbro), M. (2012). SNX9, SNX18 and SNX33 are required for progression through and completion of mitosis. Journal of Cell Science, 125(18), 4372-4382. [More Information]
  • Joshi, S., Braithwaite, A., Robinson, P., Chircop (nee Fabbro), M. (2011). Dynamin inhibitors induce caspase-mediated apoptosis following cytokinesis failure in human cancer cells and this is blocked by Bcl-2 overexpression. Molecular Cancer, 10(78), 1-12. [More Information]
  • Chircop (nee Fabbro), M., Perera, S., Mariana, A., Lau, H., Ma, M., Gilbert, J., Jones, N., Gordon, C., Young, K., Morokoff, A., Robinson, P., et al (2011). Inhibition of dynamin by dynole 34-2 induces cell death following cytokinesis failure in cancer cells. Molecular Cancer Therapeutics, 10(9), 1553-1562. [More Information]
  • Chircop (nee Fabbro), M., Sarcevic, B., Larsen, M., Malladi, C., Chau, N., Zavortink, M., Smith, C., Quan, A., Anggono, V., Hains, P., Graham, M., Robinson, P. (2011). Phosphorylation of dynamin II at serine-764 is associated with cytokinesis. BBA: Biochimica et Biophysica Acta - Molecular Cell Research, 1813 (10), 1689-1699. [More Information]
  • Von Kleist, L., Stahlschmidt, W., Bulut, H., Gromova, K., Puchkov, D., Robertson, M., Kylie, M., MacGregor, K., Tomilin, N., et al, Chau, N., Chircop (nee Fabbro), M., Robinson, P. (2011). Role of the Clathrin Terminal Domain in Regulating Coated Pit Dynamics Revealed by Small Molecule Inhibition. Cell, 146(3), 471-484. [More Information]
  • Chircop (nee Fabbro), M., Malladi, C., Lian, A., Page, S., Zavortink, M., Gordon, C., McCluskey, A., Robinson, P. (2010). Calcineurin activity is required for the completion of cytokinesis. Cellular and Molecular Life Sciences, 67(21), 3725-3737. [More Information]
  • Joshi, S., Perera, S., Gilbert, J., Smith, C., Mariana, A., Gordon, C., Sarkoff, J., McCluskey, A., Robinson, P., Braithwaite, A., Chircop (nee Fabbro), M. (2010). The Dynamin Inhibitors MiTMAB and OcTMAB Induce Cytokinesis Failure and Inhibit Cell Proliferation in Human Cancer Cells. Molecular Cancer Therapeutics, 9(7), 1995-2006. [More Information]
  • Hill, T., Gordon, C., McGeachie, A., Venn-Brown, B., Odell, L., Chau, N., Quan, A., Mariana, A., Sakoff, J., Chircop (nee Fabbro), M., Robinson, P., et al (2009). Inhibition of dynamin mediated endocytosis by the dynoles--synthesis and functional activity of a family of indoles. Journal of Medicinal Chemistry, 52(12), 3762-73. [More Information]
  • Chircop (nee Fabbro), M., Oakes, V., Graham, M., Ma, M., Smith, C., Robinson, P., Khanna, K. (2009). The actin-binding and bundling protein, EPLIN, is required for cytokinesis. Cell Cycle, 8(5), 757-764. [More Information]
  • Chircop (nee Fabbro), M., Henderson, B. (2008). BARD1 regulates BRCA1-mediated transactivation of the p21WAF1/CIP1 and Gadd45 promoters. Cancer Letters, 263(2), 189-196. [More Information]
  • Chircop (nee Fabbro), M., Zhou, B., Takahashi, M., Sarcevic, B., Lal, P., Graham, M., Gabrielli, B., Robinson, P., Nigg, E., Ono, Y., et al (2005). Cdk1/Erk2- and Plk1-dependent phosphorylation of a centrosome protein, Cep55, is required for its recruitment to midbody and cytokinesis. Developmental Cell, 9(4), 477-488. [More Information]
  • Chircop (nee Fabbro), M., Schuechner, S., Au, W., Henderson, B. (2004). Bard1 Regulates Brca1 Apoptotic Function By A Mechanism Involving Nuclear Retention. Experimental Cell Research: emphasizing molecular approaches to cell biology, 298(2), 661-673.
  • Rodriguez, J., Schuchner, S., Au, W., Chircop (nee Fabbro), M., Henderson, B. (2004). Nuclear-Cytoplasmic Shuttling Of Bard1 Contributes To Its Proapoptotic Activity And Is Regulated By Dimerization With Brca1. Oncogene, 23(10), 1809-1820.
  • Chircop (nee Fabbro), M., Henderson, B. (2003). Regulation of tumor suppressors by nuclear-cytoplasmic shuttling. Experimental Cell Research: emphasizing molecular approaches to cell biology, 282(2), 59-69.
  • Chircop (nee Fabbro), M., Rodriguez, J., Baer, R., Henderson, B. (2002). BARD1 induces BRCA1 intranuclear foci formation by increasing RING-dependent BRCA1 nuclear import and inhibiting BRCA1 nuclear export. Journal of Biological Chemistry, 277(24), 21315-21324.

2013

  • McCluskey, A., Daniel, J., Hadzic, G., Chau, N., Clayton, E., Mariana, A., Whiting, A., Gorgani, N., Lloyd, J., Quan, A., Moshkanbaryans, L., Krishnan, S., Perera, S., Chircop (nee Fabbro), M., Robinson, P., et al (2013). Building a better dynasore: the dyngo compounds potently inhibit dynamin and endocytosis. Traffic (Malden), 14(12), 1272-1289. [More Information]
  • Boutros, R., Mondesert, O., Lorenzo, C., Astuti, P., McArthur, G., Chircop (nee Fabbro), M., Ducommun, B., Gabrielli, B. (2013). CDC25B Overexpression Stabilises Centrin 2 and Promotes the Formation of Excess Centriolar Foci. PLoS One, 8(7), 1-13. [More Information]
  • Gordon, C., Venn-Brown, B., Robertson, M., Young, K., Chau, N., Mariana, A., Whiting, A., Chircop (nee Fabbro), M., Robinson, P., McCluskey, A. (2013). Development of second-generation indole-based dynamin GTPase inhibitors. Journal of Medicinal Chemistry, 56(1), 46-59. [More Information]
  • Smith, C., Haucke, V., McCluskey, A., Robinson, P., Chircop (nee Fabbro), M. (2013). Inhibition of clathrin by pitstop 2 activates the spindle assembly checkpoint and induces cell death in dividing HeLa cancer cells. Molecular Cancer, 12(4), 1-15. [More Information]
  • McGeachie, A., Odell, L., Quan, A., Daniel, J., Chau, N., Hill, T., Gorgani, N., Keating, D., Cousin, M., van Dam, E., Whiting, A., Perera, S., Novelle, A., Chircop (nee Fabbro), M., Robinson, P., et al (2013). Pyrimidyn Compounds: Dual-Action Small Molecule Pyrimidine-Based Dynamin Inhibitors. ACS Chemical Biology, 8(7), 1507-1518. [More Information]
  • Ma, M., Robinson, P., Chircop (nee Fabbro), M. (2013). Sorting Nexin 9 Recruits Clathrin Heavy Chain to the Mitotic Spindle for Chromosome Alignment and Segregation. PLoS One, 8(7), 1-11. [More Information]

2012

  • Smith, C., Chircop (nee Fabbro), M. (2012). Clathrin-Mediated Endocytic Proteins are Involved in Regulating Mitotic Progression and Completion. Traffic (Malden), 13(12), 1628-1641. [More Information]
  • Chircop (nee Fabbro), M. (2012). Protein Phosphatases Drive Mitotic Exit. In Gabriela Da Silva Xavier (Eds.), Protein Kinases, (pp. 215-228). Rijeka: InTech Publishers.
  • Ma, M., Chircop (nee Fabbro), M. (2012). SNX9, SNX18 and SNX33 are required for progression through and completion of mitosis. Journal of Cell Science, 125(18), 4372-4382. [More Information]

2011

  • Joshi, S., Braithwaite, A., Robinson, P., Chircop (nee Fabbro), M. (2011). Dynamin inhibitors induce caspase-mediated apoptosis following cytokinesis failure in human cancer cells and this is blocked by Bcl-2 overexpression. Molecular Cancer, 10(78), 1-12. [More Information]
  • Chircop (nee Fabbro), M., Perera, S., Mariana, A., Lau, H., Ma, M., Gilbert, J., Jones, N., Gordon, C., Young, K., Morokoff, A., Robinson, P., et al (2011). Inhibition of dynamin by dynole 34-2 induces cell death following cytokinesis failure in cancer cells. Molecular Cancer Therapeutics, 10(9), 1553-1562. [More Information]
  • Chircop (nee Fabbro), M., Sarcevic, B., Larsen, M., Malladi, C., Chau, N., Zavortink, M., Smith, C., Quan, A., Anggono, V., Hains, P., Graham, M., Robinson, P. (2011). Phosphorylation of dynamin II at serine-764 is associated with cytokinesis. BBA: Biochimica et Biophysica Acta - Molecular Cell Research, 1813 (10), 1689-1699. [More Information]
  • Von Kleist, L., Stahlschmidt, W., Bulut, H., Gromova, K., Puchkov, D., Robertson, M., Kylie, M., MacGregor, K., Tomilin, N., et al, Chau, N., Chircop (nee Fabbro), M., Robinson, P. (2011). Role of the Clathrin Terminal Domain in Regulating Coated Pit Dynamics Revealed by Small Molecule Inhibition. Cell, 146(3), 471-484. [More Information]

2010

  • Chircop (nee Fabbro), M., Malladi, C., Lian, A., Page, S., Zavortink, M., Gordon, C., McCluskey, A., Robinson, P. (2010). Calcineurin activity is required for the completion of cytokinesis. Cellular and Molecular Life Sciences, 67(21), 3725-3737. [More Information]
  • Joshi, S., Perera, S., Gilbert, J., Smith, C., Mariana, A., Gordon, C., Sarkoff, J., McCluskey, A., Robinson, P., Braithwaite, A., Chircop (nee Fabbro), M. (2010). The Dynamin Inhibitors MiTMAB and OcTMAB Induce Cytokinesis Failure and Inhibit Cell Proliferation in Human Cancer Cells. Molecular Cancer Therapeutics, 9(7), 1995-2006. [More Information]

2009

  • Hill, T., Gordon, C., McGeachie, A., Venn-Brown, B., Odell, L., Chau, N., Quan, A., Mariana, A., Sakoff, J., Chircop (nee Fabbro), M., Robinson, P., et al (2009). Inhibition of dynamin mediated endocytosis by the dynoles--synthesis and functional activity of a family of indoles. Journal of Medicinal Chemistry, 52(12), 3762-73. [More Information]
  • Chircop (nee Fabbro), M., Oakes, V., Graham, M., Ma, M., Smith, C., Robinson, P., Khanna, K. (2009). The actin-binding and bundling protein, EPLIN, is required for cytokinesis. Cell Cycle, 8(5), 757-764. [More Information]

2008

  • Chircop (nee Fabbro), M., Henderson, B. (2008). BARD1 regulates BRCA1-mediated transactivation of the p21WAF1/CIP1 and Gadd45 promoters. Cancer Letters, 263(2), 189-196. [More Information]

2005

  • Chircop (nee Fabbro), M., Zhou, B., Takahashi, M., Sarcevic, B., Lal, P., Graham, M., Gabrielli, B., Robinson, P., Nigg, E., Ono, Y., et al (2005). Cdk1/Erk2- and Plk1-dependent phosphorylation of a centrosome protein, Cep55, is required for its recruitment to midbody and cytokinesis. Developmental Cell, 9(4), 477-488. [More Information]

2004

  • Chircop (nee Fabbro), M., Schuechner, S., Au, W., Henderson, B. (2004). Bard1 Regulates Brca1 Apoptotic Function By A Mechanism Involving Nuclear Retention. Experimental Cell Research: emphasizing molecular approaches to cell biology, 298(2), 661-673.
  • Rodriguez, J., Schuchner, S., Au, W., Chircop (nee Fabbro), M., Henderson, B. (2004). Nuclear-Cytoplasmic Shuttling Of Bard1 Contributes To Its Proapoptotic Activity And Is Regulated By Dimerization With Brca1. Oncogene, 23(10), 1809-1820.

2003

  • Chircop (nee Fabbro), M., Henderson, B. (2003). Regulation of tumor suppressors by nuclear-cytoplasmic shuttling. Experimental Cell Research: emphasizing molecular approaches to cell biology, 282(2), 59-69.

2002

  • Chircop (nee Fabbro), M., Rodriguez, J., Baer, R., Henderson, B. (2002). BARD1 induces BRCA1 intranuclear foci formation by increasing RING-dependent BRCA1 nuclear import and inhibiting BRCA1 nuclear export. Journal of Biological Chemistry, 277(24), 21315-21324.

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