Dr Nathan Harmston
(he/him)
BSc, MSc, PhD
- Available for postgraduate supervision
Teams and roles for Nathan Harmston
Lecturer in Bioinformatics and Computational Biology
School of Biosciences
Overview
I am a computational biologist who is interested in understanding how gene expression is regulated during both development - with a focus on Drosophila - and in a disease context; specifically cancer.
My research interests encompass a variety of themes, including understanding how the 3D structure around important transcription factors influences genome evolution and identifying the genomic and epigenetic features that determine whether a gene is regulated by a specific developmental signalling pathway. My recent work has focused on better understanding the WNT signalling pathway using transcriptomic approaches.
We use a number of computational and statistical approaches to ask and answer questions about biological systems, often in close collaboration with experimental biologists.
Publication
2024
- Goh, K. Y. et al. 2024. FOXO-regulated DEAF1 controls muscle regeneration through autophagy. Autophagy 20(12), pp. 2632-2654. (10.1080/15548627.2024.2374693)
- Ang, D. A. et al. 2024. Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma. Nature Communications 15(1), article number: 2513. (10.1038/s41467-024-46728-4)
- Madan, B. et al. 2024. The cholesterol biosynthesis enzyme FAXDC2 couples Wnt/β-catenin to RTK/MAPK signaling. The Journal of Clinical Investigation 134(6), article number: e171222. (10.1172/JCI171222)
- Tan, Q. H., Otgonbaatar, A., Kaur, P., Ga, A. F., Harmston, N. P. and Tolwinski, N. S. 2024. The Wnt co-receptor PTK7/Otk and Its Homolog Otk-2 in neurogenesis and patterning. Cells 13(5), article number: 365. (10.3390/cells13050365)
2022
- Zhong, Z., Harmston, N., Wood, K. C., Madan, B. and Virshup, M. 2022. A p300/GATA6 axis determines differentiation and Wnt dependency in pancreatic cancer models. Journal of Clinical Investigation 132(12), article number: e156305. (10.1172/JCI156305)
- Lusk, J. B. et al. 2022. A non-canonical Raf function is required for dorsal–ventral patterning during Drosophila embryogenesis. Scientific Reports 12, article number: 7684. (10.1038/s41598-022-11699-3)
- Kaur, P., Otgonbaatar, A., Ramamoorthy, A., Chua, E. H. Z., Harmston, N., Gruber, J. and Tolwinski, N. S. 2022. Combining stem cell rejuvenation and senescence targeting to synergistically extend lifespan. [Online]. bioRXiv. (10.1101/2022.04.21.488994) Available at: https://doi.org/10.1101/2022.04.21.488994
- Chua, E. H. Z., Yasar, S. and Harmston, N. 2022. The importance of considering regulatory domains in genome-wide analyses – the nearest gene is often wrong!. Biology Open 11(4), article number: bio059091. (10.1242/bio.059091)
- Kaur, P., Chua, E. H. Z., Lim, W. K., Liu, J., Harmston, N. and Tolwinski, N. 2022. Wnt signaling rescues amyloid beta-induced gut stem cell loss. Cells 11(2), article number: 281. (10.3390/cells11020281)
2021
- Harmston, N., Lim, S. Y. J., Arqués, O., Palmer, H. G., Petretto, E., Virshup, D. M. and Madan, B. 2021. Widespread repression of gene expression in cancer by a Wnt/β-Catenin/MAPK pathway. Cancer Research 81(2), pp. 464-475. (10.1158/0008-5472.CAN-20-2129)
2020
- Yu, J. et al. 2020. The functional landscape of patient-derived RNF43 mutations predicts sensitivity to Wnt inhibition. Cancer Research 80(24), pp. 5619-5632. (10.1158/0008-5472.CAN-20-0957)
- Kaur, A. et al. 2020. WNT inhibition creates a BRCA-like state in Wnt-addicted cancer. [Online]. bioRXiv: bioRXiv. (10.1101/2020.06.17.157024) Available at: https://doi.org/10.1101/2020.06.17.157024
- Yu, J., Yuso, P. . A. B. M., Goh, P., Harmston, N., Epstein, D. M., Virship, D. M. and Madan, B. 2020. The functional landscape of patient derived RNF43 mutations predicts Wnt inhibitor sensitivity. [Online]. bioRXiv: bioRXiv. (10.1101/2020.03.25.006999) Available at: https://doi.org/10.1101/2020.03.25.006999
- Yapp, L. et al. 2020. In vivo generation of post-infarct human cardiac muscle by laminin-promoted cardiovascular progenitors.. Cell Reports 26(12), pp. 3231-3245. (10.1016/j.celrep.2019.02.083)
- Liu, S. et al. 2020. Wnt-regulated lncRNA discovery enhanced by in vivo identification and CRISPRi functional validation. [Online]. BioRXiv. (10.1101/2020.02.09.941005) Available at: https://doi.org/10.1101/2020.02.09.941005
2019
- Idris, M., Harmston, N., Petretto, E., Madan, B. and Virshup, D. M. 2019. Broad regulation of gene isoform expression by Wnt signaling in cancer. RNA 25(12), pp. 1696-1713. (10.1261/rna.071506.119)
- Chen, H. et al. 2019. WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling.. Nature Communications 10, article number: 3616. (10.1038/s41467-019-11551-9)
- Bardile, C. F. et al. 2019. Intrinsic mutant HTT-mediated defects in oligodendroglia cause myelination deficits and behavioral abnormalities in Huntington disease. Proceedings of the National Academy of Sciences of the United States of America 116(19), pp. 9622-9627. (10.1073/pnas.1818042116)
- Ooi, J. et al. 2019. Unbiased profiling of Isogenic Huntington Disease hPSC-Derived CNS and peripheral cells reveals strong cell-type specificity of CAG length effects. Cell Reports 26(9), pp. 2494-2508. (10.1016/j.celrep.2019.02.008)
- Bagnati, M. et al. 2019. Systems genetics identifies a macrophage cholesterol network associated with physiological wound healing.. JCI Insight 4(2), article number: 2379-3708. (10.1172/jci.insight.125736)
2018
- Madan, B., Harmston, N., Nallan, G., Montoya, A., Faull, P., Petretto, E. and Virshup, D. M. 2018. Temporal dynamics of Wnt-dependent transcriptome reveal an oncogenic Wnt/MYC/ribosome axis.. JCI Journal of Clinical Investigation 128(12), pp. 5620-5633. (10.1172/JCI122383)
- Tjin, M. S. et al. 2018. Biologically relevant laminin as chemically defined and fully human platform for human epidermal keratinocyte culture.. Nature Communications 9, article number: 4432. (10.1038/s41467-018-06934-3)
- Moreno-Moral, A. et al. 2018. Changes in macrophage transcriptome associate with systemic sclerosis and mediate GSDMA contribution to disease risk.. Annals of the Rheumatic Diseases 77, pp. 596-601. (10.1136/annrheumdis-2017-212454)
2017
- Suresh, J. et al. 2017. An embryonic system to assess direct and indirect Wnt transcriptional targets.. Scientific Reports 7, article number: 11092. (10.1038/s41598-017-11519-z)
- Harmston, N., Ing-Simmons, E., Tan, G., Perry, M., Merkenschlager, M. and Lenhard, B. 2017. Topologically associated domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation. Nature Communications 8, article number: 441. (10.1101/042952)
- Alok, A. et al. 2017. Wnt proteins synergize to activate β-catenin signaling. Development 144(10), pp. e1.1-e1.1. (10.1242/dev.154112)
- Rackham, O. J. L. et al. 2017. A Bayesian approach for analysis of whole-genome Bisulfite sequencing data identifies disease-associated changes in DNA Methylation.. Genetics 205(4), pp. 1443–1458. (10.1534/genetics.116.195008)
- Rackham, O. J. L. et al. 2017. A Bayesian approach for analysis of whole-genome bisulphite sequencing data identifies disease-associated changes in DNA methylation. [Online]. BioRXiv. (10.1101/041715) Available at: https://doi.org/10.1101/041715
2016
- Madan, B. et al. 2016. Wnt addiction of genetically defined cancers reversed by PORCN inhibition.. Oncogene 35, pp. 2197-2207. (10.1038/onc.2015.280)
- Rackham, J. O. et al. 2016. Approximate Bayesian bisulphite sequencing analysis. [Online]. BioRxiv. (10.1101/041715) Available at: https://doi.org/10.1101/041715
2015
- Harmston, N., Ing-Simmons, E., Perry, M., Barešić, A. and Lenhard, B. 2015. GenomicInteractions: An R/Bioconductor package for manipulating and investigating chromatin interaction data. BMC Genomics 16(1), article number: 963. (10.1186/s12864-015-2140-x)
2013
- Harmston, N., Barešić, A. and Lenhard, B. 2013. The mystery of extreme non-coding conservation.. Philosophical Transactions of the Royal Society B: Biological Sciences 368(1632), article number: 20130021. (10.1098/rstb.2013.0021)
- Harmston, N. and Lenhard, B. 2013. Chromatin and epigenetic features of long-range gene regulation.. Nucleic Acids Research 41(15), pp. 7185-7199. (10.1093/nar/gkt499)
2011
- Harmston, N., Filsell, W. and Stumpf, M. P. 2011. Which species is it? Species-driven gene name disambiguation using random walks over a mixture of adjacency matrices.. Bioinformatics 28(2), pp. 254-260. (10.1093/bioinformatics/btr640)
2010
- Harmston, N., Filsell, W. and Stumpf, M. P. 2010. What the papers say: Text mining for genomics and systems biology. Human Genomics 5(1), article number: 17. (10.1186/1479-7364-5-1-17)
Articles
- Goh, K. Y. et al. 2024. FOXO-regulated DEAF1 controls muscle regeneration through autophagy. Autophagy 20(12), pp. 2632-2654. (10.1080/15548627.2024.2374693)
- Ang, D. A. et al. 2024. Aberrant non-canonical NF-κB signalling reprograms the epigenome landscape to drive oncogenic transcriptomes in multiple myeloma. Nature Communications 15(1), article number: 2513. (10.1038/s41467-024-46728-4)
- Madan, B. et al. 2024. The cholesterol biosynthesis enzyme FAXDC2 couples Wnt/β-catenin to RTK/MAPK signaling. The Journal of Clinical Investigation 134(6), article number: e171222. (10.1172/JCI171222)
- Tan, Q. H., Otgonbaatar, A., Kaur, P., Ga, A. F., Harmston, N. P. and Tolwinski, N. S. 2024. The Wnt co-receptor PTK7/Otk and Its Homolog Otk-2 in neurogenesis and patterning. Cells 13(5), article number: 365. (10.3390/cells13050365)
- Zhong, Z., Harmston, N., Wood, K. C., Madan, B. and Virshup, M. 2022. A p300/GATA6 axis determines differentiation and Wnt dependency in pancreatic cancer models. Journal of Clinical Investigation 132(12), article number: e156305. (10.1172/JCI156305)
- Lusk, J. B. et al. 2022. A non-canonical Raf function is required for dorsal–ventral patterning during Drosophila embryogenesis. Scientific Reports 12, article number: 7684. (10.1038/s41598-022-11699-3)
- Chua, E. H. Z., Yasar, S. and Harmston, N. 2022. The importance of considering regulatory domains in genome-wide analyses – the nearest gene is often wrong!. Biology Open 11(4), article number: bio059091. (10.1242/bio.059091)
- Kaur, P., Chua, E. H. Z., Lim, W. K., Liu, J., Harmston, N. and Tolwinski, N. 2022. Wnt signaling rescues amyloid beta-induced gut stem cell loss. Cells 11(2), article number: 281. (10.3390/cells11020281)
- Harmston, N., Lim, S. Y. J., Arqués, O., Palmer, H. G., Petretto, E., Virshup, D. M. and Madan, B. 2021. Widespread repression of gene expression in cancer by a Wnt/β-Catenin/MAPK pathway. Cancer Research 81(2), pp. 464-475. (10.1158/0008-5472.CAN-20-2129)
- Yu, J. et al. 2020. The functional landscape of patient-derived RNF43 mutations predicts sensitivity to Wnt inhibition. Cancer Research 80(24), pp. 5619-5632. (10.1158/0008-5472.CAN-20-0957)
- Yapp, L. et al. 2020. In vivo generation of post-infarct human cardiac muscle by laminin-promoted cardiovascular progenitors.. Cell Reports 26(12), pp. 3231-3245. (10.1016/j.celrep.2019.02.083)
- Idris, M., Harmston, N., Petretto, E., Madan, B. and Virshup, D. M. 2019. Broad regulation of gene isoform expression by Wnt signaling in cancer. RNA 25(12), pp. 1696-1713. (10.1261/rna.071506.119)
- Chen, H. et al. 2019. WWP2 regulates pathological cardiac fibrosis by modulating SMAD2 signaling.. Nature Communications 10, article number: 3616. (10.1038/s41467-019-11551-9)
- Bardile, C. F. et al. 2019. Intrinsic mutant HTT-mediated defects in oligodendroglia cause myelination deficits and behavioral abnormalities in Huntington disease. Proceedings of the National Academy of Sciences of the United States of America 116(19), pp. 9622-9627. (10.1073/pnas.1818042116)
- Ooi, J. et al. 2019. Unbiased profiling of Isogenic Huntington Disease hPSC-Derived CNS and peripheral cells reveals strong cell-type specificity of CAG length effects. Cell Reports 26(9), pp. 2494-2508. (10.1016/j.celrep.2019.02.008)
- Bagnati, M. et al. 2019. Systems genetics identifies a macrophage cholesterol network associated with physiological wound healing.. JCI Insight 4(2), article number: 2379-3708. (10.1172/jci.insight.125736)
- Madan, B., Harmston, N., Nallan, G., Montoya, A., Faull, P., Petretto, E. and Virshup, D. M. 2018. Temporal dynamics of Wnt-dependent transcriptome reveal an oncogenic Wnt/MYC/ribosome axis.. JCI Journal of Clinical Investigation 128(12), pp. 5620-5633. (10.1172/JCI122383)
- Tjin, M. S. et al. 2018. Biologically relevant laminin as chemically defined and fully human platform for human epidermal keratinocyte culture.. Nature Communications 9, article number: 4432. (10.1038/s41467-018-06934-3)
- Moreno-Moral, A. et al. 2018. Changes in macrophage transcriptome associate with systemic sclerosis and mediate GSDMA contribution to disease risk.. Annals of the Rheumatic Diseases 77, pp. 596-601. (10.1136/annrheumdis-2017-212454)
- Suresh, J. et al. 2017. An embryonic system to assess direct and indirect Wnt transcriptional targets.. Scientific Reports 7, article number: 11092. (10.1038/s41598-017-11519-z)
- Harmston, N., Ing-Simmons, E., Tan, G., Perry, M., Merkenschlager, M. and Lenhard, B. 2017. Topologically associated domains are ancient features that coincide with Metazoan clusters of extreme noncoding conservation. Nature Communications 8, article number: 441. (10.1101/042952)
- Alok, A. et al. 2017. Wnt proteins synergize to activate β-catenin signaling. Development 144(10), pp. e1.1-e1.1. (10.1242/dev.154112)
- Rackham, O. J. L. et al. 2017. A Bayesian approach for analysis of whole-genome Bisulfite sequencing data identifies disease-associated changes in DNA Methylation.. Genetics 205(4), pp. 1443–1458. (10.1534/genetics.116.195008)
- Madan, B. et al. 2016. Wnt addiction of genetically defined cancers reversed by PORCN inhibition.. Oncogene 35, pp. 2197-2207. (10.1038/onc.2015.280)
- Harmston, N., Ing-Simmons, E., Perry, M., Barešić, A. and Lenhard, B. 2015. GenomicInteractions: An R/Bioconductor package for manipulating and investigating chromatin interaction data. BMC Genomics 16(1), article number: 963. (10.1186/s12864-015-2140-x)
- Harmston, N., Barešić, A. and Lenhard, B. 2013. The mystery of extreme non-coding conservation.. Philosophical Transactions of the Royal Society B: Biological Sciences 368(1632), article number: 20130021. (10.1098/rstb.2013.0021)
- Harmston, N. and Lenhard, B. 2013. Chromatin and epigenetic features of long-range gene regulation.. Nucleic Acids Research 41(15), pp. 7185-7199. (10.1093/nar/gkt499)
- Harmston, N., Filsell, W. and Stumpf, M. P. 2011. Which species is it? Species-driven gene name disambiguation using random walks over a mixture of adjacency matrices.. Bioinformatics 28(2), pp. 254-260. (10.1093/bioinformatics/btr640)
- Harmston, N., Filsell, W. and Stumpf, M. P. 2010. What the papers say: Text mining for genomics and systems biology. Human Genomics 5(1), article number: 17. (10.1186/1479-7364-5-1-17)
Websites
- Kaur, P., Otgonbaatar, A., Ramamoorthy, A., Chua, E. H. Z., Harmston, N., Gruber, J. and Tolwinski, N. S. 2022. Combining stem cell rejuvenation and senescence targeting to synergistically extend lifespan. [Online]. bioRXiv. (10.1101/2022.04.21.488994) Available at: https://doi.org/10.1101/2022.04.21.488994
- Kaur, A. et al. 2020. WNT inhibition creates a BRCA-like state in Wnt-addicted cancer. [Online]. bioRXiv: bioRXiv. (10.1101/2020.06.17.157024) Available at: https://doi.org/10.1101/2020.06.17.157024
- Yu, J., Yuso, P. . A. B. M., Goh, P., Harmston, N., Epstein, D. M., Virship, D. M. and Madan, B. 2020. The functional landscape of patient derived RNF43 mutations predicts Wnt inhibitor sensitivity. [Online]. bioRXiv: bioRXiv. (10.1101/2020.03.25.006999) Available at: https://doi.org/10.1101/2020.03.25.006999
- Liu, S. et al. 2020. Wnt-regulated lncRNA discovery enhanced by in vivo identification and CRISPRi functional validation. [Online]. BioRXiv. (10.1101/2020.02.09.941005) Available at: https://doi.org/10.1101/2020.02.09.941005
- Rackham, O. J. L. et al. 2017. A Bayesian approach for analysis of whole-genome bisulphite sequencing data identifies disease-associated changes in DNA methylation. [Online]. BioRXiv. (10.1101/041715) Available at: https://doi.org/10.1101/041715
- Rackham, J. O. et al. 2016. Approximate Bayesian bisulphite sequencing analysis. [Online]. BioRxiv. (10.1101/041715) Available at: https://doi.org/10.1101/041715
Teaching
I am currently involving in teaching computational biology and data analysis skills as part of the Big Data Biology MSc.
Previous teaching roles
Assistant Professor @ Yale-NUS
- Scientific Inquiry I
- Statistics for Life Sciences
- Computational and Systems Biology
- Advanced topics in Computational and Systems Biology
Biography
Academic positions
Previous positions
- Assistant Professor @ Yale-NUS, Singapore - 2019-2023
- Assistant Professor @ Duke-NUS, Singapore - 2019-2023
- Senior Research Fellow @ Duke-NUS, Singapore - 2015-2019
- Career Development Fellow @ MRC CSC (now LMS), London, 2012-2015
Education
- PhD @ Imperial College London (2008-2012)
- MSc - Bioinformatics and Theoretical Systems Biology - Imperial College London - (2007 - 2008)
- BSc (Hons) - Computer Science - University of Nottingham - (2002 - 2006)
Committees and reviewing
Reviewer for multiple journals
Member of Committee for Academic Integrity @ Yale-NUS - 2021 - 2022
Supervisions
Current supervision
Kieran Howard
Contact Details
Research themes
Specialisms
- Bioinformatics and computational biology
- Genomics and transcriptomics