Dr Oliver Maddocks

  • Senior Research Fellow (Experimental Therapeutics)

Biography

Oliver D. K. Maddocks is a Cancer Research UK (CRUK) Research Fellow and Group Leader at The University of Glasgow Institute of Cancer Sciences. Dr. Maddocks received a Master of Pharmacy (MPharm) degree from Cardiff University in 2003, and subsequently completed clinical training in the NHS. After a brief period as a clinical pharmacist Dr. Maddocks undertook a PhD at The University of Edinburgh Institute of Genetics and Molecular Medicine, investigating to role of pathogenic bacteria in colorectal cancer carcinogenesis. In 2008 Dr. Maddocks was awarded a Fulbright Scholarship to undertake a post-doctoral position at the University of Maryland School of Medicine, Baltimore, USA. On returning to the UK in 2010 Dr. Maddocks joined the lab of Prof. Karen Vousden as a post-doc at the CRUK Beatson Institute, working on cancer metabolism.  In 2015 Dr. Maddocks was awarded a CRUK Career Development Fellowship to start his own cancer metabolism lab at the University of Glasgow. Dr. Maddocks was recipient of the 2016 British Association for Cancer Research AstraZeneca/Frank Rose Young Scientist Prize for his contribution to cancer research.

Research interests

CANCER METABOLISM

How do cancer cells obtain and utilise nutrients, and how they deal with waste / by-product metabolites?

The growth & proliferation of cancer cells is fundamentally dependent on metabolic processes, and tumours frequently display altered metabolism compared with healthy tissues. To sustain enhanced growth, cancer cells become highly dependent on the uptake of exogenous nutrients, particularly amino acids. Additionally, by-products of up-regulated metabolic pathways must be released to maintain favourable metabolite concentration gradients and avoid toxicity. Metabolic processes can also underpin the close interaction between tumour cells and surrounding cancer-associated stromal cells.

 

While cancer related metabolic adaptations can fuel tumour growth they can also provide clinical opportunities:

  • Limiting the supply of exogenous nutrients to cancer cells, either by modulating their dietary availability or import, has the potential to both impede tumour growth and to sensitise tumours to conventional treatment.
  • Understanding the specific pathways cancer cells use to utilise nutrients and exchange metabolites with host cells could offer novel therapeutic targets.
  • Altered tumour metabolism causes systemic metabolic alterations (detectable in biological samples such as blood and urine) that could be used to improve cancer diagnosis and clinical decision-making.



We use liquid-chromatography mass spectrometry  (LCMS) analysis to conduct targeted and un-targeted metabolomics to better understand how tumours take up, use and release metabolites.

 

ATTENTION FOR OUR WORK

CRUK 2017 Patient's Pick

http://scienceblog.cancerresearchuk.org/2017/12/20/2017-cancer-research-highlights-a-patients-pick/

CRUK Video

Press

https://www.thetimes.co.uk/article/diet-free-of-amino-acids-shown-to-starve-cancer-cells-smvt9fwjt

BACR-AstraZeneca-Frank Rose Award

https://www.gla.ac.uk/researchinstitutes/cancersciences/news/headline_500323_en.html

 

SELECTED PAPERS

Serine and functional metabolites in cancer. Newman, A. C. & Maddocks, O. D.K. (2017) Trends in Cell Biology, 27(9), pp. 645-657. www.cell.com/trends/cell-biology/fulltext/S0962-8924(17)30075-2

 

Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Maddocks, O. D.K. et al. (2017)  Nature, 544(7650), pp. 372-376.  www.nature.com/articles/nature22056

 

Serine metabolism supports the methionine cycle and DNA/RNA methylation through de novo ATP synthesis in cancer cells.  Maddocks, O. D.K. et al. (2016)  Molecular Cell, 61(2), pp. 210-221. www.cell.com/molecular-cell/fulltext/S1097-2765(15)00970-3

Publications

List by: Type | Date

Jump to: 2020 | 2019 | 2018 | 2017 | 2016 | 2015 | 2014 | 2013 | 2012 | 2011 | 2009 | 2008
Number of items: 27.

2020

Papalazarou, V., Zhang, T., Paul, N. R., Juin, A., Cantini, M. , Maddocks, O. D.K. , Salmeron-Sanchez, M. and Machesky, L. (2020) The creatine-phosphagen system is mechanoresponsive in pancreatic adenocarcinoma and fuels invasion and metastasis. Nature Metabolism, 2(1), pp. 62-80. (doi: 10.1038/s42255-019-0159-z)

2019

Greenwood, H. E. et al. (2019) Measurement of tumor antioxidant capacity and prediction of chemotherapy resistance in preclinical models of ovarian cancer by positron emission tomography. Clinical Cancer Research, 25(8), pp. 2471-2482. (doi: 10.1158/1078-0432.CCR-18-3423) (PMID:30651275)

Newman, A. C., Labuschagne, C. F., Vousden, K. H. and Maddocks, O. D.K. (2019) Use of 13C315N1-serine or 13C315N1-methionine for studying methylation dynamics in cancer cell metabolism and epigenetics. In: Haznadar, M. (ed.) Cancer Metabolism: Methods and Protocols. Series: Methods in molecular biology (1928). Humana Press ; Springer: New York, NY, pp. 55-67. ISBN 9781493990269 (doi:10.1007/978-1-4939-9027-6_4)

Scopelliti, A., Bauer, C. , Yu, Y., Zhang, T., Kruspig, B., Murphy, D. J. , Vidal, M., Maddocks, O. D.K. and Cordero, J. B. (2019) A neuronal relay mediates a nutrient responsive gut/fat body axis regulating energy homeostasis in adult Drosophila. Cell Metabolism, 29(2), 269-284.e10. (doi: 10.1016/j.cmet.2018.09.021) (PMID:30344016) (PMCID:PMC6370946)

McCormick, P. N. et al. (2019) Assessment of tumor redox status through (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid positron emission tomography imaging of system xc- activity. Cancer Research, 79(4), pp. 853-863. (doi: 10.1158/0008-5472.CAN-18-2634) (PMID:30401715) (PMCID:PMC6379064)

2018

Humpton, T. J., Hock, A. K., Maddocks, O. D.K. and Vousden, K. H. (2018) p53-mediated adaptation to serine starvation is retained by a common tumour-derived mutant. Cancer and Metabolism, 6, 18. (doi: 10.1186/s40170-018-0191-6) (PMID:30524726) (PMCID:PMC6276204)

Oakey, L. A. et al. (2018) Metabolic tracing reveals novel adaptations to skeletal muscle cell energy production pathways in response to NAD+ depletion. Wellcome Open Research, 3, 147. (doi: 10.12688/wellcomeopenres.14898.1) (PMID:30607371) (PMCID:PMC6305244)

Zhang, T., Labuschagne, C. F., Vousden, K. H. and Maddocks, O. D.K. (2018) Direct estimation of metabolic flux by heavy isotope labeling simultaneous with pathway inhibition: metabolic flux inhibition assay. In: Fendt, S.-M. and Lunt, S. Y. (eds.) Metabolic Signalling: Methods and Protocols. Series: Methods in molecular biology (1862). Humana Press: New York, pp. 109-119. ISBN 9781493987689 (doi:10.1007/978-1-4939-8769-6_8)

2017

Newman, A. C. and Maddocks, O. D.K. (2017) Serine and functional metabolites in cancer. Trends in Cell Biology, 27(9), pp. 645-657. (doi: 10.1016/j.tcb.2017.05.001) (PMID:28601431)

Carroll, B. et al. (2017) Persistent mTORC1 signaling in cell senescence results from defects in amino acid and growth factor sensing. Journal of Cell Biology, 216(7), pp. 1949-1957. (doi: 10.1083/jcb.201610113) (PMID:28566325) (PMCID:PMC5496614)

Newman, A. C. and Maddocks, O. D.K. (2017) One-carbon metabolism in cancer. British Journal of Cancer, 116(2), pp. 1499-1504. (doi: 10.1038/bjc.2017.118) (PMID:28472819) (PMCID:PMC5518849)

Maddocks, O. D.K. et al. (2017) Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature, 544(7650), pp. 372-376. (doi: 10.1038/nature22056) (PMID:28425994)

2016

Meiser, J. et al. (2016) Serine one-carbon catabolism with formate overflow. Science Advances, 2(10), e1601273. (doi: 10.1126/sciadv.1601273) (PMID:27819051) (PMCID:PMC5091358)

Carroll, B. et al. (2016) Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity. eLife, 5, e11058. (doi: 10.7554/eLife.11058) (PMID:26742086) (PMCID:PMC4764560)

Maddocks, O. D.K. , Labuschagne, C. F., Adams, P. D. and Vousden, K. H. (2016) Serine metabolism supports the methionine cycle and DNA/RNA methylation through de novo ATP synthesis in cancer cells. Molecular Cell, 61(2), pp. 210-221. (doi: 10.1016/j.molcel.2015.12.014) (PMID:26774282) (PMCID:PMC4728077)

2015

Deschoemaeker, S. et al. (2015) PHD1 regulates p53-mediated colorectal cancer chemoresistance. EMBO Molecular Medicine, 7(10), pp. 1350-65. (doi: 10.15252/emmm.201505492) (PMID:26290450) (PMCID:PMC4604688)

Buescher, J. M. et al. (2015) A roadmap for interpreting 13C metabolite labeling patterns from cells. Current Opinion in Biotechnology, 34, pp. 189-201. (doi: 10.1016/j.copbio.2015.02.003) (PMID:25731751) (PMCID:PMC4552607)

2014

Maddocks, O. D.K. , Labuschagne, C. F. and Vousden, K. H. (2014) Localization of NADPH production: a wheel within a wheel. Molecular Cell, 55(2), pp. 158-160. (doi: 10.1016/j.molcel.2014.07.001)

Labuschagne, C. F., Van Den Broek, N. J.F., Mackay, G. M., Vousden, K. H. and Maddocks, O. D.K. (2014) Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. Cell Reports, 7(4), pp. 1248-1258. (doi: 10.1016/j.celrep.2014.04.045)

Hock, A. K., Lee, P., Maddocks, O. D. , Mason, S. M., Blyth, K. and Vousden, K. H. (2014) iRFP is a sensitive marker for cell number and tumor growth in high-throughput systems. Cell Cycle, 13(2), pp. 220-226. (doi: 10.4161/cc.26985)

2013

Berkers, C. R., Maddocks, O. D.K. , Cheung, E. C., Mor, I. and Vousden, K. H. (2013) Metabolic regulation by p53 family members. Cell Metabolism, 18(5), pp. 617-633. (doi: 10.1016/j.cmet.2013.06.019) (PMID:23954639) (PMCID:PMC3824073)

Maddocks, O. D. K. , Scanlon, K. M. and Donnenberg, M. S. (2013) An Escherichia coli effector protein promotes host mutation via depletion of DNA mismatch repair proteins. mBio, 4(3), e00152-13. (doi: 10.1128/mBio.00152-13) (PMID:23781066) (PMCID:PMC3684829)

Maddocks, O.D.K. , Berkers, C.R., Mason, S.M., Zheng, L., Blyth, K. , Gottlieb, E. and Vousden, K.H. (2013) Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature, 493(7433), pp. 542-546. (doi: 10.1038/nature11743)

2012

Chaneton, B. et al. (2012) Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature, 491(7424), pp. 458-462. (doi: 10.1038/nature11540)

2011

Maddocks, O.D.K. and Vousden, K.H. (2011) Metabolic regulation by p53. Journal of Molecular Medicine, 89(3), pp. 237-245. (doi: 10.1007/s00109-011-0735-5)

2009

Maddocks, O. D.K. , Short, A. J., Donnenberg, M. S., Bader, S. and Harrison, D. J. (2009) Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans. PLoS ONE, 4(5), e5517. (doi: 10.1371/journal.pone.0005517) (PMID:19436735) (PMCID:PMC2677459)

2008

Patek, C. E. et al. (2008) Effects on kidney disease, fertility and development in mice inheriting a protein-truncating Denys-Drash syndrome allele (Wt1tmT396). Transgenic Research, 17(3), pp. 459-475. (doi: 10.1007/s11248-007-9157-0) (PMID:18040647)

This list was generated on Thu Sep 17 02:14:27 2020 BST.
Jump to: Articles | Book Sections
Number of items: 27.

Articles

Papalazarou, V., Zhang, T., Paul, N. R., Juin, A., Cantini, M. , Maddocks, O. D.K. , Salmeron-Sanchez, M. and Machesky, L. (2020) The creatine-phosphagen system is mechanoresponsive in pancreatic adenocarcinoma and fuels invasion and metastasis. Nature Metabolism, 2(1), pp. 62-80. (doi: 10.1038/s42255-019-0159-z)

Greenwood, H. E. et al. (2019) Measurement of tumor antioxidant capacity and prediction of chemotherapy resistance in preclinical models of ovarian cancer by positron emission tomography. Clinical Cancer Research, 25(8), pp. 2471-2482. (doi: 10.1158/1078-0432.CCR-18-3423) (PMID:30651275)

Scopelliti, A., Bauer, C. , Yu, Y., Zhang, T., Kruspig, B., Murphy, D. J. , Vidal, M., Maddocks, O. D.K. and Cordero, J. B. (2019) A neuronal relay mediates a nutrient responsive gut/fat body axis regulating energy homeostasis in adult Drosophila. Cell Metabolism, 29(2), 269-284.e10. (doi: 10.1016/j.cmet.2018.09.021) (PMID:30344016) (PMCID:PMC6370946)

McCormick, P. N. et al. (2019) Assessment of tumor redox status through (S)-4-(3-[18F]fluoropropyl)-L-glutamic acid positron emission tomography imaging of system xc- activity. Cancer Research, 79(4), pp. 853-863. (doi: 10.1158/0008-5472.CAN-18-2634) (PMID:30401715) (PMCID:PMC6379064)

Humpton, T. J., Hock, A. K., Maddocks, O. D.K. and Vousden, K. H. (2018) p53-mediated adaptation to serine starvation is retained by a common tumour-derived mutant. Cancer and Metabolism, 6, 18. (doi: 10.1186/s40170-018-0191-6) (PMID:30524726) (PMCID:PMC6276204)

Oakey, L. A. et al. (2018) Metabolic tracing reveals novel adaptations to skeletal muscle cell energy production pathways in response to NAD+ depletion. Wellcome Open Research, 3, 147. (doi: 10.12688/wellcomeopenres.14898.1) (PMID:30607371) (PMCID:PMC6305244)

Newman, A. C. and Maddocks, O. D.K. (2017) Serine and functional metabolites in cancer. Trends in Cell Biology, 27(9), pp. 645-657. (doi: 10.1016/j.tcb.2017.05.001) (PMID:28601431)

Carroll, B. et al. (2017) Persistent mTORC1 signaling in cell senescence results from defects in amino acid and growth factor sensing. Journal of Cell Biology, 216(7), pp. 1949-1957. (doi: 10.1083/jcb.201610113) (PMID:28566325) (PMCID:PMC5496614)

Newman, A. C. and Maddocks, O. D.K. (2017) One-carbon metabolism in cancer. British Journal of Cancer, 116(2), pp. 1499-1504. (doi: 10.1038/bjc.2017.118) (PMID:28472819) (PMCID:PMC5518849)

Maddocks, O. D.K. et al. (2017) Modulating the therapeutic response of tumours to dietary serine and glycine starvation. Nature, 544(7650), pp. 372-376. (doi: 10.1038/nature22056) (PMID:28425994)

Meiser, J. et al. (2016) Serine one-carbon catabolism with formate overflow. Science Advances, 2(10), e1601273. (doi: 10.1126/sciadv.1601273) (PMID:27819051) (PMCID:PMC5091358)

Carroll, B. et al. (2016) Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity. eLife, 5, e11058. (doi: 10.7554/eLife.11058) (PMID:26742086) (PMCID:PMC4764560)

Maddocks, O. D.K. , Labuschagne, C. F., Adams, P. D. and Vousden, K. H. (2016) Serine metabolism supports the methionine cycle and DNA/RNA methylation through de novo ATP synthesis in cancer cells. Molecular Cell, 61(2), pp. 210-221. (doi: 10.1016/j.molcel.2015.12.014) (PMID:26774282) (PMCID:PMC4728077)

Deschoemaeker, S. et al. (2015) PHD1 regulates p53-mediated colorectal cancer chemoresistance. EMBO Molecular Medicine, 7(10), pp. 1350-65. (doi: 10.15252/emmm.201505492) (PMID:26290450) (PMCID:PMC4604688)

Buescher, J. M. et al. (2015) A roadmap for interpreting 13C metabolite labeling patterns from cells. Current Opinion in Biotechnology, 34, pp. 189-201. (doi: 10.1016/j.copbio.2015.02.003) (PMID:25731751) (PMCID:PMC4552607)

Maddocks, O. D.K. , Labuschagne, C. F. and Vousden, K. H. (2014) Localization of NADPH production: a wheel within a wheel. Molecular Cell, 55(2), pp. 158-160. (doi: 10.1016/j.molcel.2014.07.001)

Labuschagne, C. F., Van Den Broek, N. J.F., Mackay, G. M., Vousden, K. H. and Maddocks, O. D.K. (2014) Serine, but not glycine, supports one-carbon metabolism and proliferation of cancer cells. Cell Reports, 7(4), pp. 1248-1258. (doi: 10.1016/j.celrep.2014.04.045)

Hock, A. K., Lee, P., Maddocks, O. D. , Mason, S. M., Blyth, K. and Vousden, K. H. (2014) iRFP is a sensitive marker for cell number and tumor growth in high-throughput systems. Cell Cycle, 13(2), pp. 220-226. (doi: 10.4161/cc.26985)

Berkers, C. R., Maddocks, O. D.K. , Cheung, E. C., Mor, I. and Vousden, K. H. (2013) Metabolic regulation by p53 family members. Cell Metabolism, 18(5), pp. 617-633. (doi: 10.1016/j.cmet.2013.06.019) (PMID:23954639) (PMCID:PMC3824073)

Maddocks, O. D. K. , Scanlon, K. M. and Donnenberg, M. S. (2013) An Escherichia coli effector protein promotes host mutation via depletion of DNA mismatch repair proteins. mBio, 4(3), e00152-13. (doi: 10.1128/mBio.00152-13) (PMID:23781066) (PMCID:PMC3684829)

Maddocks, O.D.K. , Berkers, C.R., Mason, S.M., Zheng, L., Blyth, K. , Gottlieb, E. and Vousden, K.H. (2013) Serine starvation induces stress and p53-dependent metabolic remodelling in cancer cells. Nature, 493(7433), pp. 542-546. (doi: 10.1038/nature11743)

Chaneton, B. et al. (2012) Serine is a natural ligand and allosteric activator of pyruvate kinase M2. Nature, 491(7424), pp. 458-462. (doi: 10.1038/nature11540)

Maddocks, O.D.K. and Vousden, K.H. (2011) Metabolic regulation by p53. Journal of Molecular Medicine, 89(3), pp. 237-245. (doi: 10.1007/s00109-011-0735-5)

Maddocks, O. D.K. , Short, A. J., Donnenberg, M. S., Bader, S. and Harrison, D. J. (2009) Attaching and effacing Escherichia coli downregulate DNA mismatch repair protein in vitro and are associated with colorectal adenocarcinomas in humans. PLoS ONE, 4(5), e5517. (doi: 10.1371/journal.pone.0005517) (PMID:19436735) (PMCID:PMC2677459)

Patek, C. E. et al. (2008) Effects on kidney disease, fertility and development in mice inheriting a protein-truncating Denys-Drash syndrome allele (Wt1tmT396). Transgenic Research, 17(3), pp. 459-475. (doi: 10.1007/s11248-007-9157-0) (PMID:18040647)

Book Sections

Newman, A. C., Labuschagne, C. F., Vousden, K. H. and Maddocks, O. D.K. (2019) Use of 13C315N1-serine or 13C315N1-methionine for studying methylation dynamics in cancer cell metabolism and epigenetics. In: Haznadar, M. (ed.) Cancer Metabolism: Methods and Protocols. Series: Methods in molecular biology (1928). Humana Press ; Springer: New York, NY, pp. 55-67. ISBN 9781493990269 (doi:10.1007/978-1-4939-9027-6_4)

Zhang, T., Labuschagne, C. F., Vousden, K. H. and Maddocks, O. D.K. (2018) Direct estimation of metabolic flux by heavy isotope labeling simultaneous with pathway inhibition: metabolic flux inhibition assay. In: Fendt, S.-M. and Lunt, S. Y. (eds.) Metabolic Signalling: Methods and Protocols. Series: Methods in molecular biology (1862). Humana Press: New York, pp. 109-119. ISBN 9781493987689 (doi:10.1007/978-1-4939-8769-6_8)

This list was generated on Thu Sep 17 02:14:27 2020 BST.

Grants

Grants and Awards listed are those received whilst working with the University of Glasgow.

  • Increasing the susceptibility of neuroblastoma cells to radiotherapy by targeting glycolysis and lipogenesis
    Children with Cancer UK
    2021 - 2024
     
  • Mattia Falcone Fellowship
    European Molecular Biology Organization
    2019 - 2021
     
  • Targeting Tumour Metabolism for Cancer Therapy and Diagnosis
    Cancer Research UK
    2018 - 2021
     
  • Metabolic drivers of pancreatic cancer cell migration and metastasis
    Medical Research Council
    2018 - 2020
     
  • Targeting Tumour Metabolism for Cancer Therapy and Diagnosis.
    Cancer Research UK
    2015 - 2018
     

Research datasets

Jump to: 2019 | 2018
Number of items: 2.

2019

Scopelliti, A., Bauer, C., Yu, Y., Zhang, T., Kruspig, B., Murphy, D. , Vidal, M., Maddocks, O. and Cordero, J. (2019) A Neuronal Relay Mediates a Nutrient Responsive Gut/Fat Body Axis Regulating Energy Homeostasis in Adult Drosophila. [Data Collection]

2018

Maddocks, O. , Athineos, D., Cheung, E. C., Lee, P., Zhang, T., van den Broek, N. J.F., Mackay, G., Labuschagne, C. F., Gay, D., Kruiswijk, F., Blagih, J., Vincent, D., Campbell, K., Ceteci, F., Sansom, O. , Blyth, K. and Vousden, K. (2018) Modulating the therapeutic response of tumours to dietary serine and glycine starvation. [Data Collection]

This list was generated on Tue Jun 15 16:54:59 2021 BST.

Dr Oliver Maddocks