We seek to understand the fundamentals of DNA repair pathways in both somatic and reproductive cells. Our particular focus is the Fanconi anaemia pathway, which is essential for repair of crosslinked DNA. Building on advances that we and other groups are making, we identify and characterise potential new treatments for diseases that are caused by problems of DNA repair.
Another focus of the team is how molecular pathways that maintain genome stability in somatic cells also regulate repair of double-strand breaks at meiosis. The orchestrated formation and repair of these breaks are used to generate genetic diversity and keep chromosome numbers constant from one generation to the next.
Members of our laboratory have established a support group with families affected by Fanconi anaemia (FA). The organisation, FASA, is membership-driven and aims to unite and inform the FA community in Australia, New Zealand and beyond.
Current research projects
Development of targeted therapeutics for cancer and rare disease
When one genetic pathway is mutated (e.g. BRCA1/2), there can be an increased reliance on another second genetic pathway (e.g. PARP). This second pathway can be targeted in the case of certain cancers and exploits a weakness of the cancer. This relationship is known as synthetic lethality. We are discovering new synthetic lethal relationships in the DNA damage response and are developing the therapeutic tools to exploit them.The role of FANCM in mammalian reproduction
We investigate the FANCM protein, which is required for normal fertility and meiosis. FANCM can remodel a range of unique DNA structures, particularly structures that occur during DNA replication and repair. FANCM is similarly important to keep a number of serious diseases at bay.Novel inhibitors of DNA repair as chemotherapy sensitisers in breast cancer
Using our knowledge of how DNA repair proteins interact, we have designed new inhibitors that can sensitise cancer cells to chemotherapy. We are working to improve these inhibitors so that they may one day be useful in cancer treatment.Understanding the molecular mechanisms of cancer predisposition and reducing the burden of common cancers in Australia
People with Fanconi anaemia (FA), mouth cancer remains a serious problem. People with FA develop mouth cancer at much younger ages than in the general population and often without any known cause. When discovered early, mouth cancer can be treated relatively easily, but treatment becomes much more difficult when cancer is found at later stages. New methods are being developed to detect very early signs of mouth cancer in simple, non-invasive ways. One of these methods involves brushing samples from the mouth with soft brushes and testing these samples for abnormal cells.
We are currently conducting a research study to see if this test would be helpful for people with FA. We are also interested in learning more about molecules in the saliva that could indicate the presence of cancer, and in improving research collaboration in FA. We are recruiting people with FA to help with this research study, by participating in one or more of the following: donating a small blood sample, brushing certain places in the mouth with soft brushes under our guidance, completing a health questionnaire, and keeping in touch with us.
We would greatly appreciate your help with this project. If you think you might be interested in joining or want to learn more, please contact Wayne Crismani firstname.lastname@example.org
- Dr Mansura Akter, Senior Research Assistant
- Elissah Granger, Research Assistant
- Tasneem Nawab, MSc student
- Dr Vanessa Tsui
- Hannah Fluhler
- Emma Zivkovic
- Dr Adam Thomas
- Jeffrey Pullin
- Dr Lucy McNeill
- James Beddoes
- Mick Curkowskyj
- Imogen Reay
- Mal Alsania
S. Novakovic, V. Tsui, T. Semple, L. Martelotto, D. J. McCarthy, and W. Crismani. SSNIP-seq: A simple and rapid method for isolation of single-sperm nucleic acid for high-throughput sequencing. PloS one, 17(9):e0275168, 2022
V. Tsui, R. Lyu, S. Novakovic, J. M. Stringer, J. E. Dunleavy, E. Granger, T. Semple, A. Leitchter, L. Martelotto, D. J. Merriner, et al. Fancm regulates meiotic double-strand break repair pathway choice in mammals. bioRxiv, 2022
M. Sharp, R. Bythell-Douglas, A. J. Deans, and W. Crismani. The Fanconi anemia ubiquitin e3 ligase complex as an anti-cancer target. Molecular Cell, 81(11):2278–2289, 2021.
R. Lyu, V. Tsui, D. J. McCarthy, and W. Crismani. Personalized genome structure via single gamete sequencing. Genome biology, 22(1):1–19, 2021.
M. Sharp, V. Murphy, S. Van Twest, W. Tan, J. Lui, K. Simpson, A. Deans, and W. Crismani. Methodology for the identification of small molecule inhibitors of the Fanconi anaemia ubiquitin E3 ligase complex. Scientific Reports, 10(7959):1–11, 2020.
Stevan Novakovic, Vanessa Tsui. SSNIP-seq: A simple and rapid method for isolation of single-sperm nucleic acid for high-throughput sequencing. PLoS One, 17(9):e0275168, 2022.
V. Tsui and W. Crismani. The Fanconi anemia pathway and fertility. Trends in Genetics, 35(3):199–214, 2019.
ORCID profile: https://orcid.org/0000-0003-0143-8293
Google Scholar profile: https://scholar.google.com.au/citations?user=JnUjaNIAAAAJ&hl=en