Research Program Overview
Nearly all cancer cells acquire abnormalities in their genomes, such as mutations, abnormal chromosome numbers (i.e., aneuploidy) and chromosomal rearrangements. This process is referred to as genomic instability. Genomic instability represents one of the most malignant features of cancer cells, because it can cause cancer, it accelerates cancer progression and it enables tumour cells to become resistant to therapies. Our laboratory aims to understand the mechanisms of genomic instability in cancer, as well as to explore how the consequences of genomic instability can lead to drug resistance or can be used as opportunities to develop new cancer treatments.
To do this, we use a broad range of wet-lab and dry-lab approaches, including molecular pathology, 2D and 3D cell models, mouse models, functional genomics, pharmacogenomics, ‘omics’ (DNA-seq, RNA-seq, scRNA-seq, SNP6 arrays) from patient samples and cell lines, computational biology, bioinformatics, systems biology and machine learning.
Current Research Projects
- Targeting aneuploidy in cancer
- Identifying new genomic targets as opportunities to treat cancer
- Identifying drug resistance loci in cancers
- Understanding how cells survive aneuploidy
Laboratory staff
Group Leader
Team Members
Postdoctoral Research Associates
- Dr Parastoo Shahrouzi
- Dr Erika Morera
Students
- Mr Ahmad Zainal Abidin
- Mr James Lay
Select Recent Publications
- Rashidieh B, Bain AL, Tria SM, Sharma S, Stewart CA, Simmons JL, Apaja PM, Duijf PHG, Finnie J, Khanna KK. Alpha-B-Crystallin overexpression is sufficient to promote tumorigenesis and metastasis in mice. Exp Hematol Oncol (2023) 12(1):4.
- Wiegmans AP, Ward A, Ivanova E, Duijf PHG, Adams MN, Najib IM, Van Oosterhout R, Sadowski MC, Kelly G, Morrical SW, O'Byrne K, Lee JS, Richard DJ. Genome instability and pressure on non-homologous end joining drives chemotherapy resistance via a DNA repair crisis switch in triple negative breast cancer. NAR Cancer (2021) 3(2):zcab022.
- Fernando M, Duijf PHG, Proctor M, Stevenson AJ, Ehmann A, Vora S, Skalamera D, Adams M, Gabrielli B. Dysregulated G2 phase checkpoint recovery pathway reduces DNA repair efficiency and increases chromosomal instability in a wide range of tumours. Oncogenesis (2021) 10(5):41.
- Janysek DC, Kim J, Duijf PHG, Dray E. Clinical use and mechanisms of resistance for PARP inhibitors in homologous recombination-deficient cancers. Transl Oncol (2021) 14(3):101012.
- Khanna KK, Duijf PHG*. Complexities of pharmacogenomic interactions in cancer. Mol Cell Oncol (2020) 7(3):1735910.
- Shukla A, Nguyen THM, Moka SB, Ellis JJ, Grady JP, Oey H, Cristino AS, Khanna KK, Kroese DP, Krause L, Dray E, Fink JL, Duijf PHG*. Chromosome arm aneuploidies shape tumour evolution and drug response. Nat Commun (2020) 11(1):449.
- Duijf PHG*, Nanayakkara D*, Nones K, Srihari S, Kalimutho M, Khanna KK. Mechanisms of genomic instability in breast cancer. Trends Mol Med (2019) 25(7):595-611.
- Kalimutho M, Nones K, Srihari S, Duijf PHG, Waddell N, Khanna KK. Patterns of Genomic Instability in Breast Cancer. Trends Pharmacol Sci (2019) 40(3):198-211.
- Lin CY, Beattie A, Baradaran B, Dray E, Duijf PHG*. Contradictory mRNA and protein misexpression of EEF1A1 in ductal breast carcinoma due to cell cycle regulation and cellular stress. Sci Rep (2018) 8(1):13904.
- Lin CY, Shukla A, Grady JP, Fink JL, Dray E, Duijf PHG*. Translocation breakpoints preferentially occur in euchromatin and acrocentric chromosomes. Cancers (2018) 10(1):13.
- Thangavelu PU, Lin CY, Vaidyanathan S, Nguyen THM, Dray E, Duijf PHG*. Overexpression of the E2F target gene CENPI promotes chromosome instability and predicts poor prognosis in estrogen receptor-positive breast cancer. Oncotarget (2017) 8(37):62167-62182.
- Thangavelu PU, Krenács T, Dray E, Duijf PHG*. In epithelial cancers, aberrant COL17A1 promoter methylation predicts its misexpression and increased invasion. Clin Epigenetics (2016) 8:120.
- Vaidyanathan S, Cato K, Tang L, Pavey S, Haass NK, Gabrielli BG, Duijf PHG*. In vivo overexpression of Emi1 promotes chromosome instability and tumorigenesis. Oncogene (2016) 35(41):5446-5455.
