The Majewski laboratory uses genomic approaches to identify germline and somatic alterations that drive cancer biology.
Ian completed a PhD in genetics at WEHI in 2008. He moved overseas to postdoc with René Bernards at the Netherlands Cancer Institute (NKI), where he studied genetic alterations in breast, colon and lung cancer, before returning to Melbourne to start his own laboratory.
Ian’s research has provided new insight into how DNA repair pathways modulate cancer risk. He is particularly interested in how different forms of DNA damage shape the earliest stages of cancer.
Australia, University of Western Australia, BSc (Hons), 2003
Australia, University of Melbourne, PhD, 2008
2012, The Boomerang Award, Australian Society for Biochemistry and Molecular Biology
2008, Victoria Fellowship, Victorian Endowment for Science Knowledge and Innovation (veski)
2015, Alfred Felton Centenary Fellowship
Fang et al., Ganciclovir-induced mutations are present in a diverse spectrum of post-transplant malignancies. Genome Medicine (2022) PMID: 36316687
Palles et al., Germline MBD4 deficiency causes a multi-tumor predisposition syndrome. American Journal of Human Genetics (2022). PMID: 35460607
Sanders et al., MBD4 guards against methylation damage and germ line deficiency predisposes to clonal hematopoiesis and early-onset AML. Blood (2018). PMID: 30049810
DiNardo et al., Molecular patterns of response and treatment failure after frontline venetoclax combinations in older patients with AML. Blood (2020). PMID: 31932844
Majewski et al., PIK3CA Mutations Are Associated With Decreased Benefit to Neoadjuvant Human Epidermal Growth Factor Receptor 2-Targeted Therapies in Breast Cancer. Journal of Clinical Oncology (2015). PMID: 25559818
Majewski et al., Identification of recurrent FGFR3 fusion genes in lung cancer through kinome-centred RNA sequencing. The Journal of Pathology 230, 270 (2013). PMID: 23661334
Majewski et al., An alpha-E-catenin (CTNNA1) mutation in hereditary diffuse gastric cancer. The Journal of Pathology 229, 621 (2013). PMID: 23208944
Majewski & Bernards, Taming the dragon: genomic biomarkers to individualize the treatment of cancer. Nature Medicine. 2011; 17, 304 (2011). PMID: 21386834
The link between DNA damage and cancer is well established, but there is growing evidence of a contribute to other diseases. This project aims to accelerate the natural decay of the genome to determine how somatic mutations contribute to ageing and disease. We will manipulate DNA repair pathways in model systems to stimulate diverse forms of DNA damage and track their influence. We will go on to study how real-world stresses, like cancer therapy or chronic inflammation modify patterns of clonal selection.
Cytidine deaminases from the APOBEC-family make a major contribution to the mutational landscape of cancers from the bladder, breast and lung. These enzymes play a key role in viral defence, but often become misdirected and can trigger thousands of mutations in cellular DNA. We are investigating how APOBEC activity is regulated, how damage from these enzymes triggers cancer and how best to treat cancers with high levels of APOBEC.
Many antiviral therapies target DNA or RNA synthesis to disrupt viral replication. It is exceedingly difficult to target such fundamental biological processes without causing collateral damage. This project will survey DNA damage from antiviral therapies, both in normal tissues and in cancers, to reveal genetic factors, transcriptional states and drug interactions that modify their impact.