Dr Anthony Cesare

Ph.D.
Children's Medical Research Institute, Head of the Genome Integrity Group
University of Sydney, Conjoint Senior Lecturer

Telephone +61 (0)2 8865 2912

Website CMRI lab website
Cesare Lab twitter feed
Academia.edu profile
Curriculum vitae Curriculum vitae

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Biographical details

Dr. Cesare is an early career independent researcher and a Cancer Institute NSW Future Research Leader. He assumed his role as head of the CMRI Genome Integrity Group in June 2013, and became a conjoint Senior Lecturer at the University of Sydney later that year. Prior to this he was a post-doctoral fellow with Prof. Jan Karlseder at the Salk Institute in La Jolla, California (8/2009 – 6/2013), and with Prof. Roger Reddel at CMRI (1/2006 – 4/2009). He completed his Ph. D. in the United States with Prof. Jack Griffith at the University of North Carolina at Chapel Hill (12/2005).

Research interests

The long-term goal of my laboratory is to understand the fundamental mechanisms used by human cells to maintain genome integrity, and how failures in these processes contribute to human disease. Currently, we are using our expertise in the field of telomere biology to study how changes in telomere structure relate to cell growth arrest in healthy cells, and conversely how changes in telomere structure cooperate with the loss of tumor suppressors to promote genomic instability and cancer. As our research base and technical capacity grows, we anticipate using our ability to modulate telomere biology as a model to study fundamental mechanisms of genome protection in human cells.

I identified that telomeres exist in three different structural states, which govern telomere-dependent tumour suppression. "Closed-state" telomeres prevent activation of the telomere DDR, while "Uncapped-state" telomeres are subjected to DNA repair activity that covalently links chromosome ends together. In between these fully protected and completely unprotected states, lies an "Intermediate-state", which is the critical feature governing telomere-dependent tumour suppression. Intermediate-state telomeres are unique in that they can activate the DNA damage response and arrest cell growth, while simultaneously inhibiting DNA repair. This enables genomically compromised cells to activate a warning signal, and stop proliferation, while simultaneously preventing further genomic instability which can lead to cancer. Moreover, intermediate-state telomeres only result in a very specific form of cell growth arrest in the G1-phase of the cell cycle through specialized DDR signalling.

I was also part of the team which identified that telomeres transition from the Closed- to the Intermediate-state during prolonged mitosis, and that this serves as a signalling mechanism to kill human cells that are exhibiting genomic instability. This discovery exposed a complex, but poorly understood, relationship between telomeres and cell division, which we continue to actively explore. Much of our research now focuses on understanding how Intermediate-state telomeres govern cell cycle arrest, and the relationship between telomere protection and mitosis.

Current projects

Telomeres areTelomeres are the protective nucleoprotein structures located at chromosome ends. They function to protect chromosome termini, and prevent activation of the DNA damage response and illicit DNA repair activity at the naturally occurring chromosome ends. As a consequence of the normal process of DNA replication, telomeres shorten each time a cell divides. In human cells, progressive telomere shortening over many cell divisions is a potent tumour suppressor mechanism that prevents unlimited cell growth in the presence of cancerous mutations. For a cell to become cancerous, it must up-regulate the mechanisms that elongate and maintain telomere length. Telomeres, therefore, play a critical role in both tumour suppression and oncogenesis.
We have opportunities in our laboratory to study telomere biology, genome stability, tumour suppression, cell signalling and mitosis, using cutting edge techniques. Projects will be tailored to applicants interests and strengths on an individual basis
Much of our research now focuses on understanding how Intermediate-state telomeres govern cell cycle arrest, and the relationship between telomere protection and mitosis. We have opportunities in our laboratory to study telomere biology, genome stability, tumour suppression, cell signalling and mitosis, using cutting edge techniques. Projects will be tailored to applicants interests and strengths on an individual basis. the protective nucleoprotein structures located at chromosome ends. They function to protect chromosome termini, and prevent activation of the DNA damage response and illicit DNA repair activity at the naturally occurring chromosome ends. As a consequence of the normal process of DNA replication, telomeres shorten each time a cell divides. In human cells, progressive telomere shortening over many cell divisions is a potent tumour suppressor mechanism that prevents unlimited cell growth in the presence of cancerous mutations. For a cell to become cancerous, it must up-regulate the mechanisms that elongate and maintain telomere length. Telomeres, therefore, play a critical role in both tumour suppression and oncogenesis.
Our laboratory has identified that telomeres exist in three different structural states, which govern telomere-dependent tumour suppression. "Closed-state" telomeres prevent activation of the telomere DDR, while "Uncapped-state" telomeres are subjected to DNA repair activity that covalently links chromosome ends together. In between these fully protected and completely unprotected states, lies an "Intermediate-state", which is the critical feature governing telomere-dependent tumour suppression. Intermediate-state telomeres are unique in that they can activate the DNA damage response and arrest cell growth, while simultaneously inhibiting DNA repair. This enables genomically compromised cells to activate a warning signal, and stop proliferation, while simultaneously preventing further genomic instability which can lead to cancer. Moreover, intermediate-state telomeres only result in a very specific form of cell growth arrest in the G1-phase of the cell cycle through specialized DDR signalling.
We were also part of the team which identified that telomeres transition from the Closed- to the Intermediate-state during prolonged mitosis, and that this serves as a signalling mechanism to kill human cells that are exhibiting genomic instability. This discovery exposed a complex, but poorly understood, relationship between telomeres and cell division, which we continue to actively explore.
Much of our research now focuses on understanding how Intermediate-state telomeres govern cell cycle arrest, and the relationship between telomere protection and mitosis. We have opportunities in our laboratory to study telomere biology, genome stability, tumour suppression, cell signalling and mitosis, using cutting edge techniques. Projects will be tailored to applicants interests and strengths on an individual basis.

Selected grants

2018

  • Targeting novel pathways in the DNA replication-stress response to kill cancer cells; Lamm-Shalem N, Cesare A; Cancer Institute New South Wales/Early Career Fellowship.

2016

  • The role of nuclear architecture in the DNA damage response; Hinde E, Cesare A; National Health and Medical Research Council (NHMRC)/Project Grants.
  • How replication stress activates the mitotic telomere DDR to kill cancer cells; Cesare A, Hayashi M; National Health and Medical Research Council (NHMRC)/Project Grants.
  • The role of nuclear architecture in the DNA damage response; Hinde E, Cesare A; National Health and Medical Research Council (NHMRC)/Project Grants.

2015

  • Targeting TRF2 function to prevent cancer cell growth; Cesare A; Cancer Institute New South Wales/Future Research Leaders Grants.
  • Kinase signalling in the Intermediate-state Telomere cell cycle Arrest Pathway (ITAP) during human ageing and in disease; Cesare A; Cancer Council New South Wales/Research Project Grants.
  • High content screening (HCS) in-cell imaging system; Robinson P, Chircop (nee Fabbro) M, Reddel R, Bryan T, Cesare A; DVC Research/Equipment Grant.

2013

  • Ubiquitin and SUMO DNA damage response signalling at deprotected telomeres during the cell cycle; Cesare A; National Health and Medical Research Council (NHMRC)/Project Grants.

Selected publications

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Journals

  • Rogers, S., McCloy, R., Parker, B., Gallego-Ortega, D., Law, A., Chin, V., Conway, J., Fey, D., Millar, E., O'Toole, S., Cesare, A., James, D., Burgess, A., et al (2018). MASTL overexpression promotes chromosome instability and metastasis in breast cancer. Oncogene, , 1-16. [More Information]
  • Van Ly, D., Low, R., Frolich, S., Bartolec, T., Kafer, G., Pickett, H., Gaus, K., Cesare, A. (2018). Telomere Loop Dynamics in Chromosome End Protection. Molecular Cell, 71(4), 510-525.e6. [More Information]
  • Hayashi, M., Cesare, A., Rivera, T., Karlseder, J. (2015). Cell death during crisis is mediated by mitotic telomere deprotection. Nature, 522(7557), 492-496. [More Information]
  • Cesare, A., Heaphy, C., O'Sullivan, R. (2015). Visualization of Telomere Integrity and Function In Vitro and In Vivo Using Immunofluorescence Techniques. Current Protocols in Cytometry, 73, 12.40.1-12.40.31. [More Information]
  • Lackner, D., Hayashi, M., Cesare, A., Karlseder, J. (2014). A genomics approach identifies senescence-specific gene expression regulation. Aging Cell, 13(5), 946-950. [More Information]
  • Cesare, A. (2014). Mitosis, double strand break repair, and telomeres: A view from the end: How telomeres and the DNA damage response cooperate during mitosis to maintain genome stability. BioEssays, 36(11), 1054-1061. [More Information]
  • Cesare, A. (2014). Mitosis, double strand break repair, and telomeres: A view from the end: How telomeres and the DNA damage response cooperate during mitosis to maintain genome stability. BioEssays, 36(11), 1054-1061. [More Information]
  • Cesare, A., Hayashi, M., Crabbe, L., Karlseder, J. (2013). The telomere deprotection response is functionally distinct from the genomic DNA damage response. Molecular Cell, 51(2), 141-155. [More Information]
  • Hayashi, M., Cesare, A., Fitzpatrick, J., Lazzerini-Denchi, E., Karlseder, J. (2012). A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest. Nature Structural and Molecular Biology, 19(4), 387-394. [More Information]
  • Cesare, A., Karlseder, J. (2012). A three-state model of telomere control over human proliferative boundaries. Current Opinion in Cell Biology, 24(6), 731-738. [More Information]
  • Kaul, Z., Cesare, A., Huschtscha-Holliday, L., Neumann, A., Reddel, R. (2012). Five dysfunctional telomeres predict onset of senescence in human cells. EMBO Reports, 13(1), 52-59. [More Information]
  • Crabbe, L., Cesare, A., Kasuboski, J., Fitzpatrick, J., Karlseder, J. (2012). Human telomeres are tethered to the nuclear envelope during postmitotic nuclear assembly. Cell Reports, 2(6), 1521-1529. [More Information]
  • Cesare, A., Reddel, R. (2010). Alternative lengthening of telomeres: models, mechanisms and implications. Nature reviews. Genetics, 11(5), 319-30. [More Information]
  • Basenko, E., Cesare, A., Iyer, S., Griffith, J., McEachern, M. (2010). Telomeric circles are abundant in the stn1-M1 mutant that maintains its telomeres through recombination. Nucleic Acids Research, 38(1), 182-189. [More Information]
  • Pickett, H., Cesare, A., Johnston, R., Neumann, A., Reddel, R. (2009). Control of telomere length by a trimming mechanism that involves generation of t-circles. EMBO Journal, 28(7), 799-809. [More Information]
  • Cesare, A., Kaul, Z., Cohen, S., Napier, C., Pickett, H., Neumann, A., Reddel, R. (2009). Spontaneous occurrence of telomeric DNA damage response in the absence of chromosome fusions. Nature Structural and Molecular Biology, 16(12), 1244-1251. [More Information]
  • Cesare, A., Groff-Vindman, C., Compton, S., McEachern, M., Griffith, J. (2008). Telomere loops and homologous recombination-dependent telomeric circles in a Kluyveromyces lactis telomere mutant strain. Molecular and Cellular Biology, 28(1), 20-29. [More Information]
  • Cesare, A., Reddel, R. (2008). Telomere uncapping and alternative lengthening of telomeres. Mechanisms of Ageing and Development, 129(1-2), 99-108. [More Information]
  • Zhong, Z., Jiang, W., Cesare, A., Neumann, A., Wadhwa, R., Reddel, R. (2007). Disruption of telomere maintenance by depletion of the MRE11/RAD50/NBS1 complex in cells that use alternative lengthening of telomeres. Journal of Biological Chemistry, 282(40), 29314-29322. [More Information]

2018

  • Rogers, S., McCloy, R., Parker, B., Gallego-Ortega, D., Law, A., Chin, V., Conway, J., Fey, D., Millar, E., O'Toole, S., Cesare, A., James, D., Burgess, A., et al (2018). MASTL overexpression promotes chromosome instability and metastasis in breast cancer. Oncogene, , 1-16. [More Information]
  • Van Ly, D., Low, R., Frolich, S., Bartolec, T., Kafer, G., Pickett, H., Gaus, K., Cesare, A. (2018). Telomere Loop Dynamics in Chromosome End Protection. Molecular Cell, 71(4), 510-525.e6. [More Information]

2015

  • Hayashi, M., Cesare, A., Rivera, T., Karlseder, J. (2015). Cell death during crisis is mediated by mitotic telomere deprotection. Nature, 522(7557), 492-496. [More Information]
  • Cesare, A., Heaphy, C., O'Sullivan, R. (2015). Visualization of Telomere Integrity and Function In Vitro and In Vivo Using Immunofluorescence Techniques. Current Protocols in Cytometry, 73, 12.40.1-12.40.31. [More Information]

2014

  • Lackner, D., Hayashi, M., Cesare, A., Karlseder, J. (2014). A genomics approach identifies senescence-specific gene expression regulation. Aging Cell, 13(5), 946-950. [More Information]
  • Cesare, A. (2014). Mitosis, double strand break repair, and telomeres: A view from the end: How telomeres and the DNA damage response cooperate during mitosis to maintain genome stability. BioEssays, 36(11), 1054-1061. [More Information]
  • Cesare, A. (2014). Mitosis, double strand break repair, and telomeres: A view from the end: How telomeres and the DNA damage response cooperate during mitosis to maintain genome stability. BioEssays, 36(11), 1054-1061. [More Information]

2013

  • Cesare, A., Hayashi, M., Crabbe, L., Karlseder, J. (2013). The telomere deprotection response is functionally distinct from the genomic DNA damage response. Molecular Cell, 51(2), 141-155. [More Information]

2012

  • Hayashi, M., Cesare, A., Fitzpatrick, J., Lazzerini-Denchi, E., Karlseder, J. (2012). A telomere-dependent DNA damage checkpoint induced by prolonged mitotic arrest. Nature Structural and Molecular Biology, 19(4), 387-394. [More Information]
  • Cesare, A., Karlseder, J. (2012). A three-state model of telomere control over human proliferative boundaries. Current Opinion in Cell Biology, 24(6), 731-738. [More Information]
  • Kaul, Z., Cesare, A., Huschtscha-Holliday, L., Neumann, A., Reddel, R. (2012). Five dysfunctional telomeres predict onset of senescence in human cells. EMBO Reports, 13(1), 52-59. [More Information]
  • Crabbe, L., Cesare, A., Kasuboski, J., Fitzpatrick, J., Karlseder, J. (2012). Human telomeres are tethered to the nuclear envelope during postmitotic nuclear assembly. Cell Reports, 2(6), 1521-1529. [More Information]

2010

  • Cesare, A., Reddel, R. (2010). Alternative lengthening of telomeres: models, mechanisms and implications. Nature reviews. Genetics, 11(5), 319-30. [More Information]
  • Basenko, E., Cesare, A., Iyer, S., Griffith, J., McEachern, M. (2010). Telomeric circles are abundant in the stn1-M1 mutant that maintains its telomeres through recombination. Nucleic Acids Research, 38(1), 182-189. [More Information]

2009

  • Pickett, H., Cesare, A., Johnston, R., Neumann, A., Reddel, R. (2009). Control of telomere length by a trimming mechanism that involves generation of t-circles. EMBO Journal, 28(7), 799-809. [More Information]
  • Cesare, A., Kaul, Z., Cohen, S., Napier, C., Pickett, H., Neumann, A., Reddel, R. (2009). Spontaneous occurrence of telomeric DNA damage response in the absence of chromosome fusions. Nature Structural and Molecular Biology, 16(12), 1244-1251. [More Information]

2008

  • Cesare, A., Groff-Vindman, C., Compton, S., McEachern, M., Griffith, J. (2008). Telomere loops and homologous recombination-dependent telomeric circles in a Kluyveromyces lactis telomere mutant strain. Molecular and Cellular Biology, 28(1), 20-29. [More Information]
  • Cesare, A., Reddel, R. (2008). Telomere uncapping and alternative lengthening of telomeres. Mechanisms of Ageing and Development, 129(1-2), 99-108. [More Information]

2007

  • Zhong, Z., Jiang, W., Cesare, A., Neumann, A., Wadhwa, R., Reddel, R. (2007). Disruption of telomere maintenance by depletion of the MRE11/RAD50/NBS1 complex in cells that use alternative lengthening of telomeres. Journal of Biological Chemistry, 282(40), 29314-29322. [More Information]

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