Honorary Fellow
Overview
Dr Seth Cheetham is a NHMRC Early Career Fellow and holds a Career Track Fellow position in the Genome Plasticity and Disease research group. After his Bachelor of Science (Hons) at the University of Queensland, he completed his PhD at the University of Cambridge, supported by the Herchel Smith Research Studentship. He joined Mater Research in 2017 and is based at the Translational Research Institute.
Seth is a molecular biologist and geneticist with a focus on molecular mechanisms of gene regulation. He has a long-term interest in the functions of the so-called ‘junk’ DNA—noncoding DNA regions scattered throughout the genome with no obvious function— and its role in human biology.
Seth’s research is uncovering new mechanisms by which this “junk” DNA could contribute to the onset and spreading of cancer, and he is particularly interested in understanding how a type of noncoding mobile DNA, known as L1 retrotransposon, is activated in cancer. He believes understanding the role of ‘junk’ DNA, including mobile DNA and pseudogenes, will be key to improving cancer diagnosis and identifying novel therapeutic targets.
Seth conducted his Honours project with Professor John Mattick AO, FAA, FTSE at the Institute for Molecular Bioscience at UQ focussed on differentiating human protein-coding and noncoding RNA transcripts. For his PhD, he joined the group of Professor Andrea Brand FRS, FMedsci at the University of Cambridge with funding from the prestigous Herchel Smith Research Studentship. He studied the functions of long noncoding RNAs (lncRNAs) in neural development and the mechanisms through which they act.
One of Seth’s most important achievements was the development of powerful techniques to map interactions between RNAs, proteins and the DNA genome in vivo and performed key discoveries about their function in cells. For example, he was the first to identify cell-type-specific lncRNA binding sites in vivo.
Seth was awarded an NHMRC Peter Doherty Early Career Fellowship to identify key factors that control mobile DNA in cancer. These factors may be potential biomarkers for cancer diagnosis and prognosis. He recently pioneered the use of long-read Nanopore sequencing to identify mobile DNA insertions and their control by DNA methylation. Seth also investigates the functions of “pseudogenes”, which are dysfunctional copies of genes, which he believes play important roles in cancer. Seth leads a team within the Genome Plasticity and Disease group, where he is primary supervisor of two PhD students and is associate supervisor of one. He has authored 14 publications, including eight as a first author and two as a corresponding author. He has published in some of the most influential molecular biology journals including Science, Molecular Cell, Nature Reviews Genetics and Nature Structural and Molecular Biology. His work has attracted funding from an NHMRC Fellowship (2019), Mater Foundation seeing grant (2019), a UQ ECR grant (2019) and the UQ Genome Innovation Hub (2020).
‘The discovery that “junk” DNA regions have important roles in biology has revolutionised our understanding of the human genome. My research applies cutting-edge approaches to understand the mechanisms through which mobile DNA and pseudogenes impact tumour initiation and progression. My ultimate research goal is to translate our growing understanding of “junk” DNAs functions to clinically relevant information”.
Publications
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Journal Article: Overcoming challenges and dogmas to understand the functions of pseudogenes
Cheetham, Seth W., Faulkner, Geoffrey J. and Dinger, Marcel E. (2020). Overcoming challenges and dogmas to understand the functions of pseudogenes. Nature Reviews Genetics, 21 (3), 191-201. doi: 10.1038/s41576-019-0196-1
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Journal Article: Targeted DamID reveals differential binding of mammalian pluripotency factors
Cheetham, Seth W., Gruhn, Wolfram H., van den Ameele, Jelle, Krautz, Robert, Southall, Tony D., Kobayashi, Toshihiro, Surani, M. Azim and Brand, Andrea H. (2018). Targeted DamID reveals differential binding of mammalian pluripotency factors. Development, 145 (20) dev170209, dev.170209. doi: 10.1242/dev.170209
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Journal Article: RNA-DamID reveals cell-type-specific binding of roX RNAs at chromatin-entry sites
Cheetham, Seth W and Brand, Andrea H (2017). RNA-DamID reveals cell-type-specific binding of roX RNAs at chromatin-entry sites. Nature structural & molecular biology, 25 (1), 109-114. doi: 10.1038/s41594-017-0006-4
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Journal Article: Insulin finds its niche
Cheetham, Seth W. and Brand, Andrea H. (2013). Insulin finds its niche. Science, 340 (6134), 817-818. doi: 10.1126/science.1238525
Grants
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Deciphering global and locus-specific regulation of LINE-1 retrotransposons in cancer
(2019–2022) NHMRC Early Career Fellowships
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Are inhibitory pseudogenes key players in cancer?
(2019) UQ Early Career Researcher
Supervision
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The role of pseudogenes in human biology and cancer
Doctor Philosophy
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Understanding the functions of human pseudogenes
Doctor Philosophy
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Deciphering global and locus-specific regulation of LINE-1 (L1) retrotransposons in cancer
Doctor Philosophy
Available Projects
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Deciphering global and locus-specific regulation of LINE-1 retrotransposons in cancer
In cancer, but not healthy cells, ~100 L1 “jumping genes” can copy and paste themselves into the human genome. L1s can contribute to cancer initiation by activating oncogenes and inactivating tumour suppressor genes and can drive tumour evolution, underpinning resistance to chemotherapy. This project aims to determine the cause of L1 activation in cancer. This project will identify novel factors that regulate L1 expression in cancer, transforming our understanding of the mechanism of L1 activation. As L1 expression is highly correlated with cancer severity, these factors may hold important prognostic and diagnostic value.
Publications
Featured Publications
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Overcoming challenges and dogmas to understand the functions of pseudogenes
Cheetham, Seth W., Faulkner, Geoffrey J. and Dinger, Marcel E. (2020). Overcoming challenges and dogmas to understand the functions of pseudogenes. Nature Reviews Genetics, 21 (3), 191-201. doi: 10.1038/s41576-019-0196-1
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Targeted DamID reveals differential binding of mammalian pluripotency factors
Cheetham, Seth W., Gruhn, Wolfram H., van den Ameele, Jelle, Krautz, Robert, Southall, Tony D., Kobayashi, Toshihiro, Surani, M. Azim and Brand, Andrea H. (2018). Targeted DamID reveals differential binding of mammalian pluripotency factors. Development, 145 (20) dev170209, dev.170209. doi: 10.1242/dev.170209
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RNA-DamID reveals cell-type-specific binding of roX RNAs at chromatin-entry sites
Cheetham, Seth W and Brand, Andrea H (2017). RNA-DamID reveals cell-type-specific binding of roX RNAs at chromatin-entry sites. Nature structural & molecular biology, 25 (1), 109-114. doi: 10.1038/s41594-017-0006-4
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Cheetham, Seth W. and Brand, Andrea H. (2013). Insulin finds its niche. Science, 340 (6134), 817-818. doi: 10.1126/science.1238525
Book Chapter
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Mapping RNA-Chromatin interactions in vivo with RNA-DamID
Cheetham, Seth W. and Brand, Andrea H. (2020). Mapping RNA-Chromatin interactions in vivo with RNA-DamID. RNA-Chromatin Interactions. (pp. 255-264) edited by Ulf Andersson Vang Ørom. New York, NY, United States: Humana Press. doi: 10.1007/978-1-0716-0680-3_18
Journal Article
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Nanopore sequencing enables comprehensive transposable element epigenomic profiling
Ewing, Adam D., Smits, Nathan, Sanchez-Luque, Francisco J., Faivre, Jamila, Brennan, Paul M., Richardson, Sandra R., Cheetham, Seth W. and Faulkner, Geoffrey J. (2020). Nanopore sequencing enables comprehensive transposable element epigenomic profiling. Molecular Cell, 80 (5), 915-928.e5. doi: 10.1016/j.molcel.2020.10.024
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Overcoming challenges and dogmas to understand the functions of pseudogenes
Cheetham, Seth W., Faulkner, Geoffrey J. and Dinger, Marcel E. (2020). Overcoming challenges and dogmas to understand the functions of pseudogenes. Nature Reviews Genetics, 21 (3), 191-201. doi: 10.1038/s41576-019-0196-1
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LINE-1 Evasion of epigenetic repression in humans
Sanchez-Luque, Francisco J., Kempen, Marie-Jeanne H.C., Gerdes, Patricia, Vargas-Landin, Dulce B., Richardson, Sandra R., Troskie, Robin-Lee, Jesuadian, J. Samuel, Cheetham, Seth W., Carreira, Patricia E., Salvador-Palomeque, Carmen, García-Cañadas, Marta, Muñoz-Lopez, Martin, Sanchez, Laura, Lundberg, Mischa, Macia, Angela, Heras, Sara R., Brennan, Paul M., Lister, Ryan, Garcia-Perez, Jose L., Ewing, Adam D. and Faulkner, Geoffrey J. (2019). LINE-1 Evasion of epigenetic repression in humans. Molecular Cell, 75 (3), 590-604.e12. doi: 10.1016/j.molcel.2019.05.024
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DamID as a versatile tool for understanding gene regulation
Aughey, Gabriel N., Cheetham, Seth W. and Southall, Tony D. (2019). DamID as a versatile tool for understanding gene regulation. Development, 146 (6) dev173666, dev173666. doi: 10.1242/dev.173666
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Targeted DamID reveals differential binding of mammalian pluripotency factors
Cheetham, Seth W., Gruhn, Wolfram H., van den Ameele, Jelle, Krautz, Robert, Southall, Tony D., Kobayashi, Toshihiro, Surani, M. Azim and Brand, Andrea H. (2018). Targeted DamID reveals differential binding of mammalian pluripotency factors. Development, 145 (20) dev170209, dev.170209. doi: 10.1242/dev.170209
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RNA-DamID reveals cell-type-specific binding of roX RNAs at chromatin-entry sites
Cheetham, Seth W and Brand, Andrea H (2017). RNA-DamID reveals cell-type-specific binding of roX RNAs at chromatin-entry sites. Nature structural & molecular biology, 25 (1), 109-114. doi: 10.1038/s41594-017-0006-4
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Gloss, Brian S., Signal, Bethany, Cheetham, Seth W., Gruhl, Franziska, Kaczorowski, Dominik C., Perkins, Andrew C. and Dinger, Marcel E. (2017). High resolution temporal transcriptomics of mouse embryoid body development reveals complex expression dynamics of coding and noncoding loci. Scientific Reports, 7 (1) 6731, 6731. doi: 10.1038/s41598-017-06110-5
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Marshall, Owen J., Southall, Tony D., Cheetham, Seth W. and Brand, Andrea H. (2016). Cell-type-specific profiling of protein-DNA interactions without cell isolation using targeted DamID with next-generation sequencing. Nature Protocols, 11 (9), 1586-1598. doi: 10.1038/nprot.2016.084
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The Evx1/Evx1as gene locus regulates anterior-posterior patterning during gastrulation
Bell, Charles C., Amaral, Paulo P., Kalsbeek, Anton, Magor, Graham W., Gillinder, Kevin R., Tangermann, Pierre, di Lisio, Lorena, Cheetham, Seth W., Gruhl, Franziska, Frith, Jessica, Tallack, Michael R., Ru, Ke-Lin, Crawford, Joanna, Mattick, John S., Dinger, Marcel E. and Perkins, Andrew C. (2016). The Evx1/Evx1as gene locus regulates anterior-posterior patterning during gastrulation. Scientific Reports, 6 (1) 26657, 26657. doi: 10.1038/srep26657
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Freedom of expression: cell-type-specific gene profiling
Otsuki, Leo, Cheetham, Seth W. and Brand, Andrea H. (2014). Freedom of expression: cell-type-specific gene profiling. Wiley Interdisciplinary Reviews: Developmental Biology, 3 (6), 429-443. doi: 10.1002/wdev.149
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Long noncoding RNAs and the genetics of cancer
Cheetham, S. W., Gruhl, F., Mattick, J. S. and Dinger, M. E. (2013). Long noncoding RNAs and the genetics of cancer. British Journal of Cancer, 108 (12), 2419-2425. doi: 10.1038/bjc.2013.233
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Cheetham, Seth W. and Brand, Andrea H. (2013). Insulin finds its niche. Science, 340 (6134), 817-818. doi: 10.1126/science.1238525
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Gascoigne, Dennis K., Cheetham, Seth W., Cattenoz, Pierre B., Clark, Michael B., Amaral, Paulo P., Taft, Ryan J., Wilhelm, Dagmar, Dinger, Marcel E. and Mattick, John S. (2012). Pinstripe: a suite of programs for integrating transcriptomic and proteomic datasets identifies novel proteins and improves differentiation of protein-coding and non-coding genes. Bioinformatics, 28 (23), 3042-3050. doi: 10.1093/bioinformatics/bts582
Grants (Administered at UQ)
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Deciphering global and locus-specific regulation of LINE-1 retrotransposons in cancer
(2019–2022) NHMRC Early Career Fellowships
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Are inhibitory pseudogenes key players in cancer?
(2019) UQ Early Career Researcher
PhD and MPhil Supervision
Current Supervision
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The role of pseudogenes in human biology and cancer
Doctor Philosophy — Principal Advisor
Other advisors:
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Understanding the functions of human pseudogenes
Doctor Philosophy — Principal Advisor
Other advisors:
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Deciphering global and locus-specific regulation of LINE-1 (L1) retrotransposons in cancer
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.
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Deciphering global and locus-specific regulation of LINE-1 retrotransposons in cancer
In cancer, but not healthy cells, ~100 L1 “jumping genes” can copy and paste themselves into the human genome. L1s can contribute to cancer initiation by activating oncogenes and inactivating tumour suppressor genes and can drive tumour evolution, underpinning resistance to chemotherapy. This project aims to determine the cause of L1 activation in cancer. This project will identify novel factors that regulate L1 expression in cancer, transforming our understanding of the mechanism of L1 activation. As L1 expression is highly correlated with cancer severity, these factors may hold important prognostic and diagnostic value.
