Dr Jens Bunt

Research Fellow

Queensland Brain Institute
j.bunt@uq.edu.au
+61 7 334 66337

Overview

I am an early career researcher and molecular biologist / geneticist working in both neurodevelopment and neuro-oncology. My main interest is to understand how transcription factors that regulate proliferation and differentiation during normal brain development, are involved in various congenital brain malformations and brain tumours. My main goal to translate this knowledge to novel therapies, improved diagnosis or prognosis for brain malformations, such as agenesis of the corpus callosum, as well as glioblastoma and other brain tumours.

In November 2012 I completed my PhD at the Academic Medical Centre (Amsterdam, the Netherlands) under the supervision of Dr Marcel Kool, a world expert in genomic research in brain tumours. This research led to the discovery of the now established molecular subgroups in medulloblastoma and the identification of OTX2 as an oncogene. I discovered that OTX2 inhibits the differentiation of tumour cells and that knockdown of this gene can induce terminal differentiation of these cells. I further identified the pathways directly controlled by OTX2 and provided potential downstream targets suitable for therapy. My work has resulted in four first-author papers (Acta Neuropathol, Int J Cancer, Mol Cancer Res, PLoS One) as well as co-authorship on highly cited papers in PLoS One and Nature.

Within the Brain Development and Disorders laboratory headed by Prof. Linda Richards, I am currently leading a research team, consisting of two PhD students, an undergraduate student, an MSc student and a research technician. We are investigating the function of the Nuclear factor one (NFI) family of transcription factors in normal brain development as well as in disease. NFI genes are important regulators of proliferation and differentiation of cortical progenitor cells and are disrupted in congenital brain malformations and brain tumours. To investigate the function of NFI, we have generated novel genetic mouse models as well as primary brain tumour xenografts. We aim to elucidate the fundamental molecular and cellular processing of NFI-driven differentiation in brain development. Using this knowledge, we try to understand the contribution of NFI disruption to disease and whether we can apply it to improve diagnosis, prognosis or treatment.

With my team, I have published in Cell Reports, Nature Genetics, Oncotarget, Development, Scientific Reports, Stem Cell Reports, the Journal of Comparative Neurology, Cancer Letters, Developmental Biology and Brain and Neuroscience Advances.

We established a number of key collaborations both locally and internationally to investigate NFI function during development and in the context of brain malformations, and as a tumour suppressor in brain cancer. I have previously been awarded a sole CI grant from the Brain Foundation. Our cancer research is currently funded by the Scott Canner Young Researcher Grant from Tour de Cure and by a donation from Ride for Rhonda.

Research Impacts

The brain is a very complex structure. The development therefore requires a very strict control on the timing and the number of each different cell type formed. Small changes in this regulation can lead to very big consequences. For instance, critical brain structures such as the corpus callosum can be absent as their building blocks are not generated on time or tumours form from cells that remain diving. Both cancer and neurodevelopment defects underlying various intellectual and behavioural problems have a huge impact on patients. We try to understand their common origin in order to provide novel therapeutic options, a clear diagnosis or more accurate prognosis.

Qualifications

  • Doctor of Medicine, University of Amsterdam
  • Master of Science, Wageningen University

Publications

View all Publications

Supervision

  • Doctor Philosophy

  • Doctor Philosophy

  • Doctor Philosophy

View all Supervision

Available Projects

  • Projects are available within the Brain Development and Disorders laboratory, headed by Professor Linda Richards, FAA, FAHMS.

    Questions that my team is working on:

    1) How do cortical progenitor cells regulate the balance between proliferation and differentiation on an epigenetic and transcriptional level. What is the role of the different transcription factor NFI family members?

    2) How does disruption of transcription factor NFI alters this balance and corticogenesis?

    3) What are the consequences of NFI disruption for brain structure, brain wiring and behaviour? Can we determine how disruption in different cell types / brain regions result in specific defects? Why do the NFI family members have different phenotypes in both mice and human?

    4) What are the other factors in this NFI pathway, including regulators and cofactors of NFI? How does NFI relate to other genes involved in corticogenesis?

    5) How does loss of NFI-driven differentiation contributes to tumorigenesis in glial tumour such as glioblastoma and pediatric brain tumours originating from progenitor cells? What is the role of loss of glial differentiation in brain tumours?

    6) Can we apply fundamental knowledge to glial differentiation to force glial tumour cells to differentiate? And, in collaboration with more translational research groups, can we use the tumours glial origin to specifically target these tumour cells for visualisation or treatment?

    For more information, please email me or Professor Linda Richards.

View all Available Projects

Publications

Featured Publications

Journal Article

  • Chen, Kok-Siong, Lim, Jonathan W. C., Richards, Linda J. and Bunt, Jens (2017) The convergent roles of the nuclear factor I transcription factors in development and cancer. Cancer Letters, 410 124-138. doi:10.1016/j.canlet.2017.09.015

  • Matuzelski, Elise, Bunt, Jens, Harkins, Danyon, Lim, Jonathan W C, Gronostajski, Richard M, Richards, Linda J, Harris, Lachlan and Piper, Michael (2017) Transcriptional regulation of Nfix by NFIB drives astrocytic maturation within the developing spinal cord.. Developmental biology, . doi:10.1016/j.ydbio.2017.10.019

  • Chen, Kok-Siong, Harris, Lachlan, Lim, Jonathan W. C. , Harvey, Tracey J. , Piper, Michael, Gronostajski, Richard M. , Richards, Linda J. and Bunt, Jens (2017) Differential neuronal and glial expression of nuclear factor I proteins in the cerebral cortex of adult mice. Journal of Comparative Neurology, 525 11: 2465-2483. doi:10.1002/cne.24206

  • Marsh, Ashley P. L., Heron, Delphine, Edwards, Timothy J., Quartier, Angelique, Galea, Charles, Nava, Caroline, Rastetter, Agnes, Moutard, Marie-Laure, Anderson, Vicki, Bitoun, Pierre, Bunt, Jens, Faudet, Anne, Garel, Catherine, Gillies, Greta, Gobius, Ilan, Guegan, Justine, Heide, Solveig, Keren, Boris, Lesne, Fabien, Lukic, Vesna, Mandelstam, Simone A., McGillivray, George, McIlroy, Alissandra, Meneret, Aurelie, Mignot, Cyril, Morcom, Laura R., Odent, Sylvie, Paolino, Annalisa, Pope, Kate, Riant, Florence, Robinson, Gail A., Spencer-Smith, Megan, Srour, Myriam, Stephenson, Sarah E. M., Tankard, Rick, Trouillard, Oriane, Welniarz, Quentin, Wood, Amanda, Brice, Alexis, Rouleau, Guy, Attie-Bitach, Tania, Delatycki, Martin B., Mandel, Jean-Louis, Amor, David J., Roze, Emmanuel, Piton, Amelie, Bahlo, Melanie, de Villemeur, Thierry Billette, Sherr, Elliott H., Leventer, Richard J., Richards, Linda J., Lockhart, Paul J. and Depienne, Christel (2017) Mutations in DCC cause isolated agenesis of the corpus callosum with incomplete penetrance. Nature Genetics, 49 4: 511-514. doi:10.1038/ng.3794

  • Gobius, Ilan, Morcom, Laura, Sua´rez, Rodrigo, Bunt, Jens, Bukshpun, Polina, Reardon, William, Dobyns, William B., Rubenstein, John L.R., Barkovich, James, Sherr, Elliott H. and Richards, Linda J. (2016) Astroglial-mediated remodeling of the interhemispheric midline is required for the formation of the corpus callosum. Cell Reports, 17 3: 735-747. doi:10.1016/j.celrep.2016.09.033

  • Stringer, Brett W., Bunt, Jens, Day, Bryan W., Barry, Guy, Jamieson, Paul R., Ensbey, Kathleen S., Bruce, Zara C., Goasdoué, Kate, Vidal, Helene, Charmsaz, Sara, Smith, Fiona M., Cooper, Leanne T., Piper, Michael, Boyd, Andrew W. and Richards, Linda J. (2016) Nuclear factor one B (NFIB) encodes a subtype-specific tumour suppressor in glioblastoma. Oncotarget, 7 20: 29306-12320. doi:10.18632/oncotarget.8720

  • Tsuyama, Jun, Bunt, Jens, Richards, Linda J., Iwanari, Hiroko, Mochizuki, Yasuhiro, Hamakubo, Takao, Shimazaki, Takuya and Okano, Hideyuki (2015) MicroRNA-153 regulates the acquisition of gliogenic competence by neural stem cells. Stem Cell Reports, 5 3: 365-377. doi:10.1016/j.stemcr.2015.06.006

  • Lim, Jonathan W. C., Donahoo, Amber-Lee S., Bunt, Jens, Edwards, Timothy J., Fenlon, Laura R., Liu, Ying, Zhou, Jing, Moldrich, Randal X., Piper, Michael, Gobius, Ilan, Bailey, Timothy L., Wray, Naomi R., Kessaris, Nicoletta, Poo, Mu-Ming, Rubenstein, John L. R. and Richards, Linda J. (2015) EMX1 regulates NRP1-mediated wiring of the mouse anterior cingulate cortex. Development, 142 21: 3746-3757. doi:10.1242/dev.119909

  • Bunt, Jens, Lim, Jonathan W., Zhao, Lu, Mason, Sharon and Richards, Linda J. (2015) PAX6 does not regulate Nfia and Nfib expression during neocortical development. Scientific Reports, 5 Art No.: 10668: . doi:10.1038/srep10668

  • Hovestadt, Volker, Jones, David T. W., Picelli, Simone, Wang, Wei, Kool, Marcel, Northcott, Paul A., Sultan, Marc, Stachurski, Katharina, Ryzhova, Marina, Warnatz, Hans-Jorg, Ralser, Meryem, Brun, Sonja, Bunt, Jens, Jager, Natalie, Kleinheinz, Kortine, Erkek, Serap, Weber, Ursula D., Bartholomae, Cynthia C., von Kalle, Christof, Lawerenz, Chris, Eils, Jurgen, Koster, Jan, Versteeg, Rogier, Milde, Till, Witt, Olaf, Schmidt, Sabine, Wolf, Stephan, Pietsch, Torsten, Rutkowski, Stefan, Scheurlen, Wolfram, Taylor, Michael D., Brors, Benedikt, Felsberg, Jorg, Reifenberger, Guido, Borkhardt, Arndt, Lehrach, Hans, Wechsler-Reya, Robert J., Eils, Roland, Yaspo, Marie-Laure, Landgraf, Pablo, Korshunov, Andrey, Zapatka, Marc, Radlwimmer, Bernhard, Pfister, Stefan M. and Lichter, Peter (2014) Decoding the regulatory landscape of medulloblastoma using DNA methylation sequencing. Nature, 510 7506: 537-541. doi:10.1038/nature13268

  • Schoenmakers, Eric F. P. M, Bunt, Jens, Hermers, Lianne, Schepens, Marga, Merkx, Gerard, Janssen, Bert, Kersten, Monique, Huys, Erik, Pauwels, Patrick, Debiec-Rychter, Maria and van Kessel, Ad Geurts (2013) Identification of CUX1 as the recurrent chromosomal band 7q22 target gene in human uterine leiomyoma. Genes Chromosomes and Cancer, 52 1: 11-23. doi:10.1002/gcc.22001

  • Bunt, Jens, Hasselt, Nancy A., Zwijnenburg, Danny A., Koster, Jan, Versteeg, Rogier and Kool, Marcel (2013) OTX2 sustains a bivalent-like state of OTX2-bound promoters in medulloblastoma by maintaining their H3K27me3 levels. Acta Neuropathologica, 125 3: 385-394. doi:10.1007/s00401-012-1069-2

  • Bunt, J., Hasselt, N. E., Zwijnenburg, D. A., Hamdi, M., Koster, J., Versteeg, R. and Kool, M. (2012) OTX2 directly activates cell cycle genes and inhibits differentiation in medulloblastoma cells. International Journal of Cancer, 131 2: E21-E32. doi:10.1002/ijc.26474

  • Bunt, Jens, Hasselt, Nancy E., Zwijnenburg, Danny A., Koster, Jan, Versteeg, Rogier and Kool, Marcel (2011) Joint binding of OTX2 and MYC in promotor regions is associated with high gene expression in medulloblastoma. PloS One, 6 10: e26058.1-e26058.9. doi:10.1371/journal.pone.0026058

  • Bunt, Jens, de Haas, Talitha G., Hasselt, Nancy E., Zwijnenburg, Danny A., Koster, Jan, Versteeg, Rogier and Kool, Marcel (2010) Regulation of cell cycle genes and induction of senescence by overexpression of OTX2 in medulloblastoma cell lines. Molecular Cancer Research, 8 10: 1344-1357. doi:10.1158/1541-7786.MCR-09-0546

  • Kool, Marcel, Koster, Jan, Bunt, Jens, Hasselt, Nancy E., Lakeman, Arjan, van Sluis, Peter, Troost, Dirk, Schouten-van Meeteren, Netteke, Caron, Huib N., Cloos, Jacqueline, Mrsic, Alan, Ylstra, Bauke, Grajkowska, Wieslawa, Hartmann, Wolfgang, Pietsch, Torsten, Ellison, David, Clifford, Steven C. and Versteeg, Rogier (2008) Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PloS One, 3 8: e3088.1-e3088.14. doi:10.1371/journal.pone.0003088

Conference Publication

  • Lambo, Sander, Bunt, Jens, Schmidt, Christine, Pfister, Stefan M., Richards, Linda J., Chavez, Lukas, Korshunov, Andrey and Kool, Marcel (2016). Genome-Wide Profiling of Embryonal Tumors with Multilayered Rosettes (Etmr). In: 17th International Symposium on Pediatric Neuro-Oncology (ISPNO), Liverpool, England, (9-9). Jun 12-15, 2016.

  • Gobius, I., Morcom, L., Suarez, R., Bunt, J., Sherr, E. and Richards, L. (2015). Astroglial-mediated remodeling of the interhemispheric midline is exclusive to eutherian mammals and underlies the formation of the corpus callosum. In: Supplement: GLIA Bilbao 2015: Abstracts Oral Presentations, Posters, Indexes. 12th European Meeting on Glial Cell Function in Health and Disease, Bilbao, Spain, (E206-E206). 15-18 July 2015. doi:10.1002/glia.22870

  • Gobius, I., Morcom, L., Suarez, R., Bunt, J., Sherr, E. H. and Richards, L. J. (2015). Astroglial-mediated remodeling of the interhemispheric midline underlies the formation of the corpus callosum in eutherian mammals. In: Special Issue: 25th Biennial Meeting of the International Society for Neurochemistry Jointly with the 13th Meeting of the Asian Pacific Society for Neurochemistry in Conjunction with the 35th Meeting of the Australasian Neuroscience Society. 25th Biennial Meeting of the International Society for Neurochemistry Jointly with the 13th Meeting of the Asian Pacific Society for Neurochemistry in Conjunction with the 35th Meeting of the Australasian Neuroscience Society, Cairns, QLD Australia, (104-104). 23-27 August 2015. doi:10.1111/jnc.13188

  • Bunt, J., Hasselt, N., Koster, J., Zwijnenburg, D., Versteeg, R. and Kool, M. (2010). Otx2 Regulates Cell Cycle Genes in Medulloblastoma. In: Neuro-Oncology. 14th International Symposium on Pediatric Neuro-Oncology, Vienna Austria, (II53-II54). Jun 20-23, 2010.

PhD and MPhil Supervision

Current Supervision

  • Doctor Philosophy — Associate Advisor

  • Doctor Philosophy — Associate Advisor

  • Doctor Philosophy — Associate Advisor

    Other advisors:

  • Doctor Philosophy — Associate Advisor

    Other advisors:

Possible Research Projects

Note for students: The possible research projects listed on this page may not be comprehensive or up to date. Always feel free to contact the staff for more information, and also with your own research ideas.

  • Projects are available within the Brain Development and Disorders laboratory, headed by Professor Linda Richards, FAA, FAHMS.

    Questions that my team is working on:

    1) How do cortical progenitor cells regulate the balance between proliferation and differentiation on an epigenetic and transcriptional level. What is the role of the different transcription factor NFI family members?

    2) How does disruption of transcription factor NFI alters this balance and corticogenesis?

    3) What are the consequences of NFI disruption for brain structure, brain wiring and behaviour? Can we determine how disruption in different cell types / brain regions result in specific defects? Why do the NFI family members have different phenotypes in both mice and human?

    4) What are the other factors in this NFI pathway, including regulators and cofactors of NFI? How does NFI relate to other genes involved in corticogenesis?

    5) How does loss of NFI-driven differentiation contributes to tumorigenesis in glial tumour such as glioblastoma and pediatric brain tumours originating from progenitor cells? What is the role of loss of glial differentiation in brain tumours?

    6) Can we apply fundamental knowledge to glial differentiation to force glial tumour cells to differentiate? And, in collaboration with more translational research groups, can we use the tumours glial origin to specifically target these tumour cells for visualisation or treatment?

    For more information, please email me or Professor Linda Richards.