Staff Profile
Dr Brian Ortmann
NUAcT Fellow: Ageing and Health
- Email: brian.ortmann@ncl.ac.uk
- Address: Centre for Cancer
Paul O'Gorman Building
Framlington Place
缅北禁地 upon Tyne
NE2 4AD
I am a 缅北禁地 Academic Track (NUAcT) fellow within the Biosciences Institute.
Past Positions:
University of Cambridge - Postdoctoral Research Assistant (2016-2022)
University of Dundee - PhD student (2011-2015)
Qualifications:
PhD in Cell Biology, University of Dundee, 2015
BSc (Hons) Biomedical Sciences, University of Dundee, 2011
Cells in the human body are constantly exposed to fluctuating oxygen levels, making oxygen availability a pivotal factor in regulating cellular function and fate. Hypoxia—defined by a reduction in oxygen supply—drives the progression of diseases such as cancer and inflammation, fuelling critical processes like metastasis and immune response resulting in poor patient outcome. Therefore, understanding how cells adapt to hypoxic conditions is vital for uncovering novel therapeutic targets and improving treatment effectiveness.
The Hypoxia-Inducible Factor (HIF) family of transcription factors play a central role in the body’s response to low oxygen. Under hypoxic conditions, HIF stabilises and activates a transcriptional programme that supports cellular survival and adaptation. However, in tumours, dysregulated HIF activity accelerates disease progression, positioning HIF as both a promising and complex therapeutic target. Despite the availability of several HIF inhibitors, the risk of systemic toxicity from blanket inhibition highlights the need for more refined, targeted approaches.
A key question in the field is how HIF activity is precisely regulated across different cellular contexts. Our research has identified SET1B, a histone methyltransferase, as a crucial HIF coactivator, suggesting that targeting co-regulators could offer a more selective means of modulating HIF. SET1B is part of a larger family of methyltransferases and demethylases—many of which are oxygen-sensitive and HIF-regulated—that modify proteins through methylation, altering their function. This indicates that methylation could play a central role in the broader hypoxia response.
While HIF activation is a critical component of the cellular response to hypoxia, it is inherently slow as a transcriptional programme and cannot account for the rapid changes’ cells need to survive in low-oxygen environments. In contrast, methylation is a fast, reversible post-translational modification capable of swiftly altering protein function. Despite its potential as a key regulator of hypoxia adaptation, the broader role of methylation in both HIF-dependent and independent pathways remains largely unexplored.
My research group uses innovative forward genetic screening and proteomics to interrogate how methylation regulates the cellular response to hypoxia. The ultimate goal of the lab is to identify new therapeutic targets to treat cancer, autoimmunity, and neurodegeneration.
I am always open to inquiries from prospective undergraduate and PhD students as well postdoctoral researchers.
Current lab members:
Dr Nikita Dhillon (Post Doctoral Researcher)
Lukasz Marzec (PhD Student)
Alexander Handyside (PhD Student)
Meagan Farrington (MRes Student)
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Articles
- Bertlin JAC, Pauzaite T, Liang Q, Wit N, Williamson JC, Sia JJ, Matheson NJ, Ortmann BM, Mitchell TJ, Speak AO, Zhang Q, Nathan JA. . bioRxiv 2024. Submitted.
- Ortmann BM. . BMJ Oncology 2024, 3(1), e000154.
- Ortmann BM, Taylor CT, Rocha S. . Trends in Biochemical Sciences 2024, 49(7), p573-582.
- Meng B, Zhao N, Mlcochova P, Ferreira IA, Ortmann BM, Davis T, Wit N, Rehwinkel J, Cook S, Maxwell PH, Nathan JA. . Cell Reports 2024, 43(7), 114471.
- Shilts J, Crozier TWM, TeixeiraSilva A, Gabaev I, Gerber PP, Greenwood EJD, Watson SJ, Ortmann BM, Gawden-Bone CM, Pauzaite T, Hoffmann M, Nathan JA, Pöhlmann S, Matheson NJ, Lehner PJ, Wright GJ. . PLOS Biology 2023, 21(2), e3001959.
- Porter LM, Guo W, Crozier TW, Greenwood EJ, Ortmann BM, Kottmann D, Nathan JA, Mahadeva R, Lehner PJ, McCaughan F. . Heliyon 2023, 9(3), e14383.
- Kotagiri P, Mescia F, Hanson AL, Turner L, Bergamaschi L, Peñalver A, Richoz N, Moore SD, Ortmann BM, Dunmore BJ, Morgan MD, Tuong ZK, Göttgens B, Toshner M, Hess C, Maxwell PH, Clatworthy MR, Nathan JA, Bradley JR, Lyons PA, Burrows N, Smith KGC. . EBioMedicine 2022, 77, 103878.
- Ortmann BM, Burrows N, Lobb IT, Arnaiz E, Wit N, Bailey PSJ, Jordon LH, Lombardi O, Peñalver A, McCaffrey J, Seear R, Mole DR, Ratcliffe PJ, Maxwell PH, Nathan JA. . Nature Genetics 2021, 53, 1022-1035.
- Ortmann BM, Nathan JA. . FEBS Journal 2021, 289(18), 5396-5412.
- Bailey PSJ, Ortmann BM, Martinelli AW, Houghton JW, Costa ASH, Burr SP, Antrobus R, Frezza C, Nathan JA. . Nature Communications 2020.
- Ono M, Yamada K, Bensaddek D, Afzal V, Biddlestone J, Ortmann B, Mudie S, Boivin V, Scott MS, Rocha S, Lamond AI. . PLoS One 2016.
- Ortmann B, Bensaddek D, Carvalhal S, Moser SC, Mudie S, Griffis E, Swedlow JR, Lamond AI, Rocha S. . Journal of Cell Science 2016.
- Ortmann B, Druker J, Rocha S. . Cell Mol Life Sci 2014.
- Moser SC, Bensaddek D, Ortmann B, Mudie S, Blow JJ, Lamond AI, Swedlow JR, Rocha S. . Developemental Cell 2013.