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 Pascal Duijf obtained a Bachelor’s degree in Biology and a Master’s degree in Medical Biology from the Radboud University Nijmegen in the Netherlands and was awarded two scholarships that enabled him to gain research experience in cell biology at Harvard Medical School in Boston, MA in the United States.

He then pursued a PhD degree in Human Molecular Genetics at the Radboud University Nijmegen Medical Centre. Under supervision of Professor Han Brunner and Professor Hans van Bokhoven, his research established genotype-phenotype correlations for a variety of human congenital disorders that are caused by germline mutations in the TP63 gene and are characterised by developmental abnormalities of the limbs, ectodermal structures and/or lip/palate.

For his postdoctoral research, Dr Duijf moved to the United States. At Memorial Sloan-Kettering Cancer Center in New York, he studied how chromosome instability and aneuploidy contribute to cancer development and progression. Using systems approaches, his research showed that cancer cells preferentially lose small chromosomes, although, paradoxically, gains of chromosomes predict poor prognosis in ovarian cancer. In addition, his research demonstrated that chromosome instability can be rescued in a p53 mutant mouse tumour model. This was a significant observation, as it indicates 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, Australia. His research focuses on identifying the causes and consequences of genomic instability in the development of cancer (see also ‘Research Interests’ below for more details). He aims to translate this knowledge into the development of cancer diagnostic, therapeutic and precision medicine approaches. To achieve this, he uses a broad range of methods, including mouse modelling, genome editing, microscopy, cell and molecular biology, molecular pathology, proteomics and computational systems genomics.

As a group leader, Dr Duijf’s contributions to the research field have included:

  1. Identification of genes whose overexpression promotes genomic instability and/or tumour development (e.g., Emi1, COL17A1, CENPI and EEF1A1) and the underlying mechanisms. PMIDs: 27065322, 27891193, 28977935, 30224719.
  2. Identification of the key genomic factors that predispose to cancerous translocations (i.e., acrocentrism and open chromatin state). PMID: 29316705.
  3. Pan-cancer identification of aneuploidies that drive tumour evolution and predict good or poor patient outcome (unpublished).
  4. Using machine learning, pan-cancer identification of genomic abnormalities that predict cancer patients’ responses to a large panel of chemotherapeutic drugs, thus improving precision oncology (unpublished).

Research Interests

  • Genomic instability in cancer
    Genomic instability refers to the acquisition of changes in the DNA or chromosomes of cells. Such changes could include mutations, deletions, amplifications, the gain or loss of whole chromosomes or parts of chromosomes, or translocations (i.e., abnormal breaks in the DNA followed by incorrect fusion). Genomic instability is common in cancer cells. It enables tumour cells to acquire a range of unwanted properties, such as the abilities to spread through the body, escape from the immune system or become resistant to cancer therapies. Dr Duijf’s research focuses on identifying the causes and consequences of genomic instability in the development of cancer. He aims to translate this knowledge into the development of cancer diagnostic, therapeutic and precision medicine approaches. To achieve this, he uses a broad range of methods, including mouse modeling, genome editing, microscopy, cell and molecular biology, molecular pathology, proteomics, and computational systems genomics.

Research Impacts

Genomic instability is a highly 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 clinical problem is likely to benefit patients with most forms of cancer.

Qualifications

  • Doctor of Philosophy, Radboud Universiteit Nijmegen

Publications

View all Publications

Supervision

View all Supervision

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

  • Safarzadeh, Elham, Hashemzadeh, Shahryar, Duijf, Pascal H. G., Mansoori, Behzad, Khaze, Vahid, Mohammadi, Ali, Kazemi, Tohid, Yousefi, Mehdi, Asadi, Milad, Mohammadi, Hamed, Babaie, Farhad and Baradaran, Behzad (2018) Circulating myeloid-derived suppressor cells: an independent prognostic factor in patients with breast cancer. Journal of Cellular Physiology, . doi:10.1002/jcp.26896

  • 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, 233 8: 5574-5588. 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, 46 7: 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: 79-121. 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