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

Map

Biographical details

Dr. Anthony (Tony) Cesare leads the CMRI Genome Integrity Unit and is a conjoint Senior Lecturer at the University of Sydney (2013 - current). Prior to directing his independent laboratory, he was a post-doctoral fellow with Prof. Jan Karlseder at the Salk Institute in La Jolla, California (2009 - 2013), and with Prof. Roger Reddel at CMRI (2006 - 2009). He completed his Ph. D. in the United States with Prof. Jack Griffith at the University of North Carolina at Chapel Hill (2005).

Research interests

Mylaboratory broadly focuses on processes that maintain genome stability in mammalian cells, and the cellular consequences when these mechanisms fail. Our current research streams are as follows:

Telomere biology:We recently identified that telomere-loops (t-loops) specifically function to regulate ATM activity at human and mouse telomeres (Van ly et al 2018Mol Cell). To accomplish this, we developed the capacity to visualize telomere structure using super-resolution microscopy. We are continuing to investigate how TRF2 regulates t-loop structure and the role of macromolecular chromosome end structure in telomere biology. Additionally, we have developed proximity labelling techniques and unbiased mass spectrometry to identify spatiotemporal regulation of telomere function. We are currently following novel leads generated through these approaches.

Replication stress response:Our lab recently made two major advances in this area. First, we identified lethal replication stress induces mitotic death in the immediately following cell division through parallel mechanisms of WAPL-dependent cohesion fatigue and telomere deprotection (Masamsetti et alBiorχiv2018).Second, we identified a novel ATR/mTOR/actin axis that alters nuclear architecture to facilitate replication stress repair (Lamm et alBiorχiv2018).Both projects rely heavily on live cell imaging, including our collaborative development of novel image analysis tools that revealed directed movement of replication foci along nuclear actin fibres as a key event in the replication stress response. To move these projects forward, our lab developed proficiency in whole genome CRISPR/Cas9 screening. We have now identified novel genetic regulators of mitotic death and replication stress repair that we are investigating in the lab. In a related project we are using live-cell imaging and CRISPR/Cas9 screening in collaboration with the Sydney West Radiation Oncology Network to elucidate mechanisms of radiation sensitivity and resistance in human cancer cells.

Genome Stability in Stem Cells: In collaboration with Patrick Tam (CMRI) we are investigating cellular mechanisms that regulate genome integrity in pluripotent stem cells.

Chromatin architecture and genome stability:In collaboration with Liz Hinde (U. Melbourne Bio21) we discovered that ATM and RNF8 regulate chromatin compaction and decompaction at double strand breaks to demarcate the repair foci from the surrounding genomic environment (Lou et alPNAS2019). The lab is now endeavouring to understand the role of chromatin remodelers in the replication stress response and double strand break repair.

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, the replication stress and DNA damage responses, cell signalling, and mitosis. Our lab employs cutting edge techniques including super-resolution microscopy, live-cell imaging, CRISPR/Cas9 whole genome screening, and proximity-labelling mass spectrometry. 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

2019

  • Telomere integrity in human health and disease; Pickett H, Cesare A; National Health and Medical Research Council (NHMRC)/Project Grants.

2018

  • Targeting novel pathways in the DNA replication-stress response to kill cancer cells; Lamm-Shalem N, Cesare A; Cancer Institute NSW/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.
  • 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.

2015

  • Targeting TRF2 function to prevent cancer cell growth; Cesare A; Cancer Institute NSW/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

Download citations: PDF RTF Endnote

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, 37(33), 4518-4533. [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, 37(33), 4518-4533. [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]

To update your profile click here. For support on your academic profile contact .