Dr Pascal Duijf

Senior Research Fellow

The University of Queensland Diamantina Institute
Faculty of Medicine
p.duijf@uq.edu.au
+61 7 344 36937

Overview

Dr Duijf first became interested in genetics and cell biology in high school. During chemistry and biology classes, his curiosity was stimulated by the processes of DNA replication, protein synthesis and cell division. In the final year of high school, his class visited a research laboratory at the local university hospital. This environment definitively sparked his fascination for biomedical research. His desire to pursue a career in this field led to his obtaining a Bachelor’s degree in Biology and a Master’s degree in Medical Biology from the Radboud University Nijmegen in the Netherlands.

Subsequently, Dr Duijf successfully applied for two scholarships. Those enabled him to gain research experience in cell biology in Professor Frank McKeon’s laboratory in the department of Cell Biology at Harvard Medical School in the United States.

To continue research training in cell biology and genetics, he returned to the Netherlands to pursue a PhD degree in Human Genetics at the Radboud University Nijmegen Medical Centre. His mentors included clinical geneticist Professor Han Brunner and molecular geneticist Professor Hans van Bokhoven. Under their supervision, he made important contributions to establishing genotype-phenotype correlations for a variety of human congenital disorders that are characterised by developmental abnormalities of the limbs, ectodermal structures and/or lip/palate. All of these disorders are caused by germline mutations in the p63 gene, a homologue of the p53 tumour suppressor gene. For his postdoctoral research, Dr Duijf changed research fields. In the laboratory of Professor Robert Benezra at Memorial Sloan-Kettering Cancer Center in New York, his research focussed on how chromosome instability contributes to cancer development and progression in vivo, using mouse models. With a particular interest in breast and childhood cancers, he demonstrated that p53 pathway defects, which are frequent in human cancers, lead to overexpression of the mitotic checkpoint gene Mad2 via crosstalk to the Rb (Retinoblastoma) pathway. In addition, he showed that chromosome instability can be rescued in a p53 mutant mouse tumour model. This was an important observation as it suggests that targeting chromosome instability in human tumours will be an effective strategy to treat cancer patients. In 2013, Dr Duijf established his independent research group at the University of Queensland Diamantina Institute and the Translational Research Institute in Brisbane. His group continues to study chromosome instability in mouse models in order to develop new strategies to improve cancer diagnosis and treatment.

Research Interests

  • Chromosome instability in cancer
    Cancer cells frequently missegregate their chromosomes during cell division. This phenomenon, termed chromosome instability, leads to the formation of aneuploid cells, i.e., cells with abnormal chromosome numbers. Chromosome instability is one of the most malignant features of cancer cells, because it can cause cancer, it accelerates cancer progression and it is an important mechanism for cancer cells to become resistant to cancer therapies. The Duijf laboratory uses in vivo mouse models and in vitro cell models in order to: (1) study how chromosome instability contributes to cancer progression and (2) identify novel mechanisms that cause chromosome instability. Chromosome missegregation has a variety of known and unknown causes and effects. Therefore, in addition to identifying new mechanisms, the group studies a range of phenomena that are known to be associated with chromosome instability, including DNA damage, mitotic checkpoint defects, sister-chromatid cohesion defects, centrosome overduplication and cytokinesis failure. With an interest in breast and other cancers, the Duijf group’s research goals are translational in nature: to develop new approaches or enhance existing ones in order to improve the diagnosis and treatment of cancer.

Research Impacts

Chromosome instability is one of the most malignant features of cancer cells, because it can cause cancer, it accelerates cancer progression and it is an important mechanism for cancer cells to become resistant to cancer therapies. Therefore, the development of a therapy that can specifically address this major clinical problem is likely to benefit patients with most forms of cancer.

Qualifications

  • Doctor of Philosophy, Radboud Universiteit Nijmegen

Publications

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Supervision

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Publications

Featured Publications

Book

Journal Article

  • Joo, Jihoon E., Dowty, James G., Milne, Roger L., Wong, Ee Ming, Dugué, Pierre-Antoine, English, Dallas, Hopper, John L., Goldgar, David E., Giles, Graham G., Southey, Melissa C., kConFab, Sexton, Adrienne, Christian, Alice, Trainer, Alison, Spigelman, Allan, Fellows, Andrew, Shelling, Andrew, De Fazio, Anna, Blackburn, Anneke, Crook, Ashley, Meiser, Bettina, Patterson, Briony, Clarke, Christine, Saunders, Christobel, Hunt, Clare, Scott, Clare, Amor, David, Marsh, Deborah, Edkins, Edward, Salisbury, Elizabeth, Haan, Eric, Neidermayr, Eveline, Macrae, Finlay, Farshid, Gelareh, Lindeman, Geoff, Chenevix-Trench, Georgia, Mann, Graham, Gill, Grantley, Thorne, Heather, Campbell, Ian, Hickie, Ian, Winship, Ingrid, Goldblatt, Jack, Flanagan, James, Kollias, James, Visvader, Jane, Stone, Jennifer, Taylor, Jessica, Burke, Jo, Saunus, Jodi, Forbes, John, Beesley, Jonathan, Kirk, Judy, French, Juliet, Tucker, Kathy, Wu, Kathy, Phillips, Kelly, Lipton, Lara, Andrews, Leslie, Lobb, Elizabeth, Walker, Logan, Kentwell, Maira, Spurdle, Amanda, Cummings, Margaret, Gleeson, Margaret, Harris, Marion, Jenkins, Mark, Young, Mary Anne, Delatycki, Martin, Wallis, Mathew, Burgess, Matthew, Price, Melanie, Brown, Melissa, Bogwitz, Michael, Field, Michael, Friedlander, Michael, Gattas, Michael, Saleh, Mona, Hayward, Nick, Pachter, Nick, Cohen, Paul, Duijf, Pascal, James, Paul, Butow, Phyllis, Simpson, Peter, Fong, Peter, Williams, Rachael, Kefford, Richard, Scott, Rodney, Balleine, Rosemary, Dawson, Sarah-Jane, Lok, Sheau, O'Connell, Shona, Greening, Sian, Nightingale, Sophie, Edwards, Stacey, Fox, Stephen, McLachlan, Sue-Anne, Lakhani, Sunil, Thomas, Susan and Antill, Yoland (2018) Heritable DNA methylation marks associated with susceptibility to breast cancer. Nature Communications, 9 1: . doi:10.1038/s41467-018-03058-6

  • Lin, Cheng-Yu, Beattie, Alexandra, Baradaran, Behzad, Dray, Eloise and Duijf, Pascal H. G. (2018) Contradictory mRNA and protein misexpression of EEF1A1 in ductal breast carcinoma due to cell cycle regulation and cellular stress. Scientific Reports, 8 1: . doi:10.1038/s41598-018-32272-x

  • Kalimutho, Murugan, Sinha, Debottam, Jeffery, Jessie, Nones, Katia, Srihari, Sriganesh, Fernando, Winnie C., Duijf, Pascal H. G., Vennin, Claire, Raninga, Prahlad, Nanayakkara, Devathri, Mittal, Deepak, Saunus, Jodi M., Lakhani, Sunil R., López, J Alejandro, Spring, Kevin J., Timpson, Paul, Gabrielli, Brian, Waddell, Nicola and Khanna, Kum Kum (2018) CEP55 is a determinant of cell fate during perturbed mitosis in breast cancer. EMBO Molecular Medicine, 10 9: e8566. doi:10.15252/emmm.201708566

  • Ghasabi, Mehri, Mansoori, Behzad, Mohammadi, Ali, Duijf, Pascal H. G., Shomali, Navid, Shirafkan, Naghmeh, Mokhtarzadeh, Ahad and Baradaran, Behzad (2018) MicroRNAs in cancer drug resistance: basic evidence and clinical applications. Journal of Cellular Physiology, . doi:10.1002/jcp.26810

  • Hosseinahli, Nayer, Aghapour, Mahyar, Duijf, Pascal H G and Baradaran, Behzad (2018) Treating cancer with microRNA replacement therapy: A literature review. Journal of Cellular Physiology, . doi:10.1002/jcp.26514

  • Lin, Cheng-Yu, Shukla, Ankit, Grady, John P. , Fink, J. Lynn, Dray, Eloise and Duijf, Pascal H.G. (2018) Translocation breakpoints preferentially occur in euchromatin and acrocentric chromosomes. Cancers, 10 1: 13. doi:10.3390/cancers10010013

  • Shajari, Neda, Davudian, Sadaf, Kazemi, Tohid, Mansoori, Behzad, Salehi, Shima, Shahgoli, Vahid Khaze, Shanehbandi, Dariush, Mohammadi, Ali, Duijf, Pascal H. G. and Baradaran, Behzad (2017) Silencing of BACH1 inhibits invasion and migration of prostate cancer cells by altering metastasis-related gene expression. Artificial Cells, Nanomedicine, and Biotechnology, 1-10. doi:10.1080/21691401.2017.1374284

  • Thangavelu, Pulari U., Lin, Cheng-Yu, Vaidyanathan, Srividya, Nguyen, Thu H. M., Dray, Eloise and Duijf, Pascal H. G. (2017) Overexpression of the E2F target gene CENPI promotes chromosome instability and predicts poor prognosis in estrogen receptor-positive breast cancer. OncoTarget, 8 37: 62167-62182. doi:10.18632/oncotarget.19131

  • Thangavelu, Pulari U., Krenács, Tibor, Dray, Eloise and Duijf, Pascal H. G. (2016) In epithelial cancers, aberrant COL17A1 promoter methylation predicts its misexpression and increased invasion. Clinical Epigenetics, 8 1: . doi:10.1186/s13148-016-0290-6

  • Vaidyanathan, Srividya, Cato, Kathleen, Tang, Lu, Pavey, Sandra, Haass, Nikolas K., Gabrielli, Brian G. and Duijf, Pascal H. G. (2016) In vivo overexpression of Emi1 promotes chromosome instability and tumorigenesis. Oncogene, 35 41: 5446-5455. doi:10.1038/onc.2016.94

  • Vaidyanathan, Srividya, Thangavelu, Pulari U. and Duijf, Pascal H. G. (2016) Overexpression of Ran GTPase components regulating nuclear export, but not mitotic spindle assembly, marks chromosome instability and poor prognosis in breast cancer. Targeted Oncology, 11 5: 677-686. doi:10.1007/s11523-016-0432-y

  • Duijf, P. H. G. and Benezra, R. (2013) The cancer biology of whole-chromosome instability. Oncogene, 32 40: 4727-4736. doi:10.1038/onc.2012.616

  • Duijf, Pascal H. G., Schultz, Nikolaus and Benezra, Robert (2013) Cancer cells preferentially lose small chromosomes. International Journal of Cancer, 132 10: 2316-2326. doi:10.1002/ijc.27924

  • Schvartzman, Juan-Manuel, Duijf, Pascal H. G., Sotillo, Rocio, Coker, Courtney and Benezra, Robert (2011) Mad2 Is a Critical Mediator of the Chromosome Instability Observed upon Rb and p53 Pathway Inhibition. Cancer Cell, 19 6: 701-714. doi:10.1016/j.ccr.2011.04.017

  • Rinne, Tuula, Clements, Suzanne E., Lamme, Evert, Duijf, Pascal H.G., Bolat, Emine, Meijer, Rowdy, Scheffer, Hans, Rosser, Elisabeth, Tan, Tiong Yang, McGrath, John A., Schalkwijk, Joost, Brunner, Han G., Zhou, Huiqing and van Bokhoven, Hans (2008) A novel translation re-initiation mechanism for the p63 gene revealed by amino-terminal truncating mutations in Rapp-Hodgkin/Hay-Wells like syndromes. Human Molecular Genetics, 17 13: 1968-1977. doi:10.1093/hmg/ddn094

  • Rinne, Tuula, Spadoni, Emanuela, Kjaer, Klaus W., Danesino, Cesare, Larizza, Daniela, Kock, Marianne, Huoponen, Kirsi, Savontaus,Marja-Liisa, Aaltonen, Markku, Duijf, Pascal, Brunner, Han G., Penttinen, Maila and van Bokhoven, Hans (2006) Delineation of the ADULT syndrome phenotype due to arginine 298 mutations of the p63 gene. European Journal of Human Genetics, 14 8: 904-910. doi:10.1038/sj.ejhg.5201640

  • Duijf, Pascal H. G. and van Bokhoven, Hans (2005) Ectodermal dysplasia: skinny models on the catwalk. Drug Discovery Today: Disease Models, 2 2: 111-118. doi:10.1016/j.ddmod.2005.05.006

  • Bongers, Ernie M. H. F., Duijf, Pascal H. G., van Beersum, Sylvia E. M., Schoots, Jeroen, van Kampen, Albert, Burckhardt, Andreas, Hamel, Ben C. J., Lošan, František, Hoefsloot, Lies H., Yntema, Helger G., Knoers, Nine V. A. M. and van Bokhoven, Hans (2004) Mutations in the human TBX4 gene cause small patella syndrome. American Journal of Human Genetics, 74 6: 1239-1248. doi:10.1086/421331

  • Duijf, Pascal H. G., van Bokhoven, Hans and Brunner, Han G. (2003) Pathogenesis of split-hand/split-foot malformation. Human Molecular Genetics, 12 Supp. 1: R51-R60. doi:10.1093/hmg/ddg090

  • Ghioni, Pamela, Bolognese, Fabrizio, Duijf, Pascal H. G., van Bokhoven, Hans, Mantovani, Roberto and Guerrini, Luisa (2002) Complex transcriptional effects of p63 isoforms: identification of novel activation and repression domains. Molecular and Cellular Biology, 22 24: 8659-8668. doi:10.1128/MCB.22.24.8659-8668.2002

  • Serber, Zack, Lai, Helen C., Yang, Annie, Ou, Horng D., Sigal, Martina S., Kelly, Alexander E., Beatrice D. Darimont,, Duijf, Pascal H. G., van Bokhoven, Hans, McKeon, Frank and Dötsch, Volker (2002) A C-terminal inhibitory domain controls the activity of p63 by an intramolecular mechanism. Molecular and Cellular Biology, 22 24: 8601-8611. doi:10.1128/MCB.22.24.8601-8611.2002

  • Duijf, Pascal H. G., Vanmolkot, Kaate R. J., Propping, Peter, Friedl, Waltraut, Krieger, Elmar, McKeon, Frank, Dötsch, Volker, Brunner, Han G. and van Bokhoven, Hans van (2002) Gain-of-function mutation in ADULT syndrome reveals the presence of a second transactivation domain in p63. Human Molecular Genetics, . doi:10.1093/hmg/11.7.799

  • Van Bokhoven, Hans, Hamel, Ben C. J., Bamshad, Mike, Sangiorgi, Eugenio, Gurrieri, Fiorella, Duijf, Pascal H. G., Vanmolkot, Kaate R. J., van Beusekom, Ellen, van Beersum, Sylvia E. C., Celli, Jacopo, Merkx, Gerard F. M., Tenconi, Romano, Fryns, Jean Pierre, Verloes, Alain, Newbury-Ecob, Ruth A., Raas-Rotschild, Annick, Majewski, Frank, Beemer, Frits A., Janecke, Andreas, Chitayat, David, Crisponi, Giangiorgio, Kayserili, Hülya, Yates, John R. W., Neri, Giovanni and Brunner, Han G. (2001) p63 Gene mutations in EEC syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation. American Journal of Human Genetics, 36 3: 481-492. doi:10.1086/323123

  • McGrath, John A., Duijf, Pascal H. G., Doetsch, Volker, Irvine, Alan D., de Waal, Rob, Vanmolkot, Kaate R. J., Wessagowit, Vesarat, Kelly, Alexander, Atherton, David J., Griffiths, W. Andrew D., Orlow, Seth J., van Haeringen, Arle, Ausems, Margaret G.E.M., Yang, Annie, McKeon, Frank, Bamshad, Michael A., Brunner, Han G., Hamel, Ben C. J. and van Bokhoven, Hans (2001) Hay-Wells syndrome is caused by heterozygous missense mutations in the SAM domain of p63. Human Molecular Genetics, 10 3: 221-229. doi:10.1093/hmg/10.3.221

  • Celli, Jacopo, Duijf, Pascal, Hamel, Ben C. J., Bamshad, Michael, Kramer, Bridget, Smits, Arie P. T., Newbury-Ecob, Ruth, Hennekam, Raoul C. M., Van Buggenhout, Griet, van Haeringen, Arie, Woods, C. Geoffrey, van Essen, Anthonie J., de Waal, Rob, Vriend, Gert, Haber, Daniel A., Yang, Annie, McKeon, Frank, Brunner, Han G. and van Bokhoven, Hans (1999) Heterozygous germline mutations in the p53 homolog p63 are the cause of EEC syndrome. Cell, 99 2: 143-153. doi:10.1016/S0092-8674(00)81646-3

Conference Publication

  • Tanaka, Kozo and Duijf, Pascal H. G. (2018). Chromosomal instability as a cause and a therapeutic target for cancer. In: 76th Annual Meeting of the Japanese Cancer Association: Prevention and Cure of Cancer through Understanding of the Networks. 76th Annual Meeting of the Japanese Cancer Association, Yokohama, Japan, (417-417). 28 - 30 September 2017.

  • Duijf, Pascal H. G., Vaidyanathan, Srividya, Cato, Kathleen, Thangavelu, Pulari U., Lin, Cheng-Yu, Tang, Lu, Pavey, Sandra, Haass, Nikolas K. and Gabrielli, Brian G. (2018). Overexpression of the cell cycle regulator Emi1 promotes chromosome instability and tumorigenesis. In: 76th Annual Meeting of the Japanese Cancer Association, Yokohama, Japan, (418-418). 28-30 September 2017. doi:10.1111/cas.13499

  • Vaidyanathan, S., Cato, K., Tang, L., Pavey, S., Haass, N. K., Gabrielli, B. G. and Duijf, P. H. G. (2016). Overexpression of Early Mitotic Inhibitor 1 (Emi1) promotes genomic instability and cancer. In: Annual Meeting of the American Society for Cell Biology (ASCB), San Francisco Ca, (). Dec 03-07, 2016.

PhD and MPhil Supervision

Note for students: Dr Pascal Duijf is not currently available to take on new students.

Current Supervision

  • Doctor Philosophy — Principal Advisor

    Other advisors:

  • Doctor Philosophy — Principal Advisor

  • Doctor Philosophy — Principal Advisor