Staff profile
Professor Adam Benham
Director of PG Studies
Affiliation | Telephone |
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Director of PG Studies in the Department of Biosciences | +44 (0) 191 33 41259 |
Biography
I graduated from St. Catherine's College, Oxford, with first class honours in Biochemistry and obtained my PhD in transplantation immunology with Prof. John Fabre at the Institute of Child Health, University College, London. I received an EU postdoctoral fellowship to study the biochemistry of antigen presentation with Prof. Jacques Neefjes at the Netherlands Cancer Institute in Amsterdam and then joined Prof. Ineke Braakman's laboratory at Utrecht University, Netherlands, to research mechanisms of protein quality control in the endoplasmic reticulum (ER).
Since establishing my laboratory at Durham University, I have been investigating both the quality control of proteins involved in antigen presentation and the machinery that controls oxidative protein folding in various cells and tissues. My laboratory is interested in how these fundamentally important biological pathways underpin human and animal health. For example, we have discovered a novel member of the Protein Disulfide Isomerase (PDI) family called PDILT that is required for sperm:egg binding (in collaboration with Osaka University, Japan). This work may lead to the development of new tests and cures for unexplained male infertility and has been covered extensively by the media. We are also working with colleagues at UNIFESP-EPM, Sao Paulo, to understand the role of the PDI family in the development and function of the male epididymis.
Our work on immune molecules (the Major Histocompatibility Complex, MHC) seeks to explain how these proteins are loaded with their peptide cargo and how oxidative protein folding and ER chaperones contribute to their quality control. This has applications in understanding neoantigen presentation and in the design of cancer vaccines. In BBSRC funded work, we have worked with Scancell, Nottingham and partners to determine the trafficking of MHC-neoantigen complexes.
Other studies in my laboratory have revealed links between the ER quality control machinery and gastrointestinal disease (in collaboration with James Cook University Hospital, Middlesbrough). We are also harnessing new microscopy and quantitative proteomics technologies (SWATH) to explore the biology of proteostasis and stress responses in the skin (in collaboration with P&G), including extracellular matrix proteins such as collagen, and pigment trafficking in melanocytes.
Alongside my research activities, I am Postgraduate Director for the Department of Biosciences, module leader for undergraduate Level 2 Immune Systems and contributer to Biology of Disease undergrauate teaching at Level 3. I am on the editorial board of the journals "Antioxidants and Redox Signaling" and "Biology Direct" and I serve on the Biochemical Society Training Theme Panel. I have been appointed as an external examiner for various undergraduate degree courses and postgraduate training programmes.
My research has been funded by the BBSRC, MRC, Wellcome Trust, Arthritis Research UK, Leverhulme Trust, Royal Society, European Union, JGWP Foundation, IBM and FAPESP (Brazil) and the support of these organisations is gratefully acknowledged.
A selection of our peer-reviewed research publications can be found below.
Research interests
- cell biology and biochemistry
- immune system
- oxidative folding of proteins in the Endoplasmic Reticulum
Publications
Chapter in book
Journal Article
- Fernandes, S. G., Ferreira, L. G. A., Benham, A. M., & Avellar, M. C. W. (online). Epididymal mRNA expression profiles for the protein disulfide isomerase gene family: Modulation by development and androgens. Andrology, https://doi.org/10.1111/andr.13700
- Tan, C. Y. R., Morenc, M., Setiawan, M., Lim, Z. Z. Y., Soon, A. L., Bierman, J. C., Vires, L., Laughlin, T., DeAngelis, Y. M., Rovito, H., Jarrold, B. B., Nguyen, T. Q. N., Lim, J. S. Y., Kent, O., Määttä, A., Benham, A. M., Hawkins, T. J., Lee, X. E., Ehrman, M. C., Oblong, J. E., …Bellanger, S. (2024). Para-Hydroxycinnamic Acid Mitigates Senescence and Inflammaging in Human Skin Models. International Journal of Molecular Sciences, 25(15), Article 8153. https://doi.org/10.3390/ijms25158153
- Young, N., Gui, Z., Mustafa, S., Papa, K., Jessop, E., Ruddell, E., Bevington, L., Quinlan, R. A., Benham, A. M., Goldberg, M. W., Obara, B., & Karakesisoglou, I. (2024). Inhibition of PDIs Downregulates Core LINC Complex Proteins, Promoting the Invasiveness of MDA-MB-231 Breast Cancer Cells in Confined Spaces In Vitro. Cells, 13(11), Article 906. https://doi.org/10.3390/cells13110906
- Fang, B., Card, P. D., Chen, J., Li, L., Laughlin, T., Jarrold, B., Zhao, W., Benham, A. M., Määttä, A. T., Hawkins, T. J., & Hakozaki, T. (2022). A Potential Role of Keratinocyte-Derived Bilirubin in Human Skin Yellowness and Its Amelioration by Sucrose Laurate/Dilaurate. International Journal of Molecular Sciences, 23(11), Article 5884. https://doi.org/10.3390/ijms23115884
- Hunter-Featherstone, E., Young, N., Chamberlain, K., Cubillas, P., Hulette, B., Wei, X., Tiesman, J. P., Bascom, C. C., Benham, A. M., Goldberg, M. W., Saretzki, G., & Karakesisoglou, I. (2021). Culturing Keratinocytes on Biomimetic Substrates Facilitates Improved Epidermal Assembly In Vitro. Cells, 10(5), https://doi.org/10.3390/cells10051177
- Worfolk, J., Bell, S., Simpson, L., Carne, N., Francis, S., Engelbertsen, V., Brown, A., Walker, J., Viswanath, Y., & Benham, A. (2019). Elucidation of the AGR2 interactome in esophageal adenocarcinoma cells identifies a redox sensitive chaperone hub for the quality control of MUC-5AC. Antioxidants and Redox Signaling, 31(15), 1117-1132. https://doi.org/10.1089/ars.2018.7647
- Carne, N., Brown, A., Bell, S., Maatta, A., Flagler, M., & Benham, A. (2019). Reductive stress selectively disrupts collagen homeostasis and modifies growth factor-independent signalling through the MAPK/Akt pathway in human dermal fibroblasts. Molecular and Cellular Proteomics, 18(6), 1123-1137. https://doi.org/10.1074/mcp.ra118.001140
- Benham, A. M. (2019). Endoplasmic Reticulum redox pathways: in sickness and in health. The FEBS Journal, 286(2), 311--321. https://doi.org/10.1111/febs.14618
- Schorr-Lenz, A., Alves, J., Hence, N., Seidel, P., Benham, A., & Bustamante-Filho, I. (2016). GnRH immunization alters the expression and distribution of protein disulfide isomerases in the epididymis. Andrology, 4(5), 957-963. https://doi.org/10.1111/andr.12205
- Tokuhiro, K., Satouh, Y., Nozawa, K., Isotani, A., Fujihara, Y., Hirashima, Y., Matsumura, H., Takumi, K., Miyano, T., Okabe, M., Benham, A., & Ikawa, M. (2015). Calreticulin is required for development of the cumulus oocyte complex and female fertility. Scientific Reports, 5, https://doi.org/10.1038/srep14254
- Tarran, W., Freeman, G., Murphy, L., Benham, A., Kataky, R., & Williams, J. (2014). Platinum(II) Complexes of N^C^N‑Coordinating 1,3-Bis(2-pyridyl)benzene Ligands: Thiolate Coligands Lead to Strong Red Luminescence from Charge-Transfer States. Inorganic Chemistry, 53(11), 5738-5749. https://doi.org/10.1021/ic500555w
- Battle, D., Dias-Gunasekara, S., Watson, G., Mohamed Ahmed, E., Saysell, C., Altaf, N., Sanusi, A., Munipalle, P., Scoones, D., Walker, J., Viswanath, Y., & Benham, A. (2013). Expression of the Endoplasmic Reticulum Oxidoreductase Ero1α in gastro-intestinal cancer reveals a link between homocysteine and oxidative protein folding. Antioxidants and Redox Signaling, 19(1), 24-45. https://doi.org/10.1089/ars.2012.4651
- Benham, A., van Lith, M., Sitia, R., & Braakman, I. (2013). Ero1-PDI interactions, the response to redox flux and the implications for disulfide bond formation in the mammalian endoplasmic reticulum. Philosophical Transactions of the Royal Society B: Biological Sciences, 368(1617), Article 20110403. https://doi.org/10.1098/rstb.2011.0403
- Tokuhiro, K., Ikawa, M., Benham, A., & Okabe, M. (2012). Protein disulfide isomerase homolog PDILT is required for quality control of sperm membrane protein ADAM3 and male fertility. Proceedings of the National Academy of Sciences, 109(10), 3850-3855. https://doi.org/10.1073/pnas.1117963109
- Benham, A. (2012). The protein disulfide isomerase family: key players in health and disease. Antioxidants and Redox Signaling, 16(8), 781-789. https://doi.org/10.1089/ars.2011.4439
- Pekovic, V., Gibbs-Seymour, I., Markiewicz, E., Alzoghaibi, F., Benham, A., Edwards, R., Wehnert, M., von Zlignicki, T., & Hutchison, C. (2011). Conserved cysteine residues in the mammalian lamin A tail are essential for cellular responses to ROS generation. Aging Cell, 10(6), 1067-1079. https://doi.org/10.1111/j.1474-9726.2011.00750.x
- Ikawa, M., Tokuhiro, K., Yamaguchi, R., Benham, A., Tamura, T., Wada, I., Satouh, Y., Inoue, N., & Okabe, M. (2011). Calsperin is a testis-specific chaperone required for sperm fertility. Journal of Biological Chemistry, 286(7), 5639-5646. https://doi.org/10.1074/jbc.m110.140152
- Ikawa, M., Inoue, N., Benham, A., & Okabe, M. (2010). Fertilization: a sperm's journey to and interaction with the oocyte. Journal of Clinical Investigation, 120(4), 984-994. https://doi.org/10.1172/jci41585
- van Lith, M., McEwen-Smith, R., & Benham, A. (2010). HLA-DP, HLA-DQ and HLA-DR have different requirements for invariant chain and HLA-DM. Journal of Biological Chemistry, 285(52), 40800-40808. https://doi.org/10.1074/jbc.m110.148155
- Benham, A. (2009). Protein folding and disulfide bond formation in the eukaryotic cell. The FEBS Journal, 276(23), 6905-11. https://doi.org/10.1111/j.1742-4658.2009.07409.x
- van Lith, M., Karala, A., Bown, D., Gatehouse, J., Ruddock, L., Saunders, P., & Benham, A. (2007). A developmentally regulated chaperone complex for the endoplasmic reticulum of male haploid germ cells. Molecular Biology of the Cell, 18(8), 2795-2804. https://doi.org/10.1091/mbc.e07-02-0147
- Lemin, A., Saleki, K., van Lith, M., & Benham, A. (2007). Activation of the unfolded protein response and alternative splicing of ATF6α in HLA-B27 positive lymphocytes. FEBS Letters, 581(9), 1819-1824. https://doi.org/10.1016/j.febslet.2007.03.069
- van Lith, M., & Benham, A. (2006). The DM and DM chain cooperate in the oxidation and folding of HLA-DM1. The Journal of Immunology, 177(8), 5430-5439
- Dias-Gunasekara, S., van Lith, M., Williams, J., Kataky, R., & Benham, A. (2006). Mutations in the FAD binding domain cause stress-induced misoxidation of the endoplasmic reticulum oxidoreductase Ero1b. Journal of Biological Chemistry, 281(35), 25018-25025. https://doi.org/10.1074/jbc.m602354200
- Saleki, K., Hartigan, N., van Lith, M., Bulleid, N., & Benham, A. (2006). Differential oxidation of HLA-B2704 and HLA-B2705 in lymphoblastoid and transfected adherent cell lines. Antioxidants and Redox Signaling, 8(3-4), 292-299. https://doi.org/10.1089/ars.2006.8.292
- Dias-Gunasekara, S., Gubbens, J., van Lith, M., Dunne, C., Williams, J., Kataky, R., Scoones, D., Lapthorn, A., Bulleid, N., & Benham, A. (2005). Tissue-specific expression and dimerization of the endoplasmic reticulum oxidoreductase Erolb. Journal of Biological Chemistry, 280(38), 33066-33075. https://doi.org/10.1074/jbc.m505023200
- van Lith, M., Hartigan, N., Hatch, J., & Benham, A. (2005). PDILT, a divergent testis-specific protein disulfide isomerase with a non-classical SXXC motif that engages in disulfide-dependent interactions in the endoplasmic reticulum. Journal of Biological Chemistry, 280(2), 1376-1383. https://doi.org/10.1074/jbc.m408651200
- Dixon, D., van Lith, M., Edwards, R., & Benham, A. (2003). Cloning and initial characterization of the Arabidopsis thaliana Endoplasmic Reticulum Oxidoreductins. Antioxidants and Redox Signaling, 5(4), 389-396. https://doi.org/10.1089/152308603768295122
- Mezghrani, A., Fassio, A., Benham, A., Simmen, T., Braakman, I., & Sitia, R. (2001). Manipulation of oxidative protein folding and PDI redox state in mammalian cells. The EMBO Journal, 20(22), 6288-6296. https://doi.org/10.1093/emboj/20.22.6288
- Benham, A., Cabibbo, A., Fassio, A., Bulleid, N., Sitia, R., & Braakman, I. (2000). The CXXCXXC motif determines the folding, structure and stability of human Ero1-La. The EMBO Journal, 19(17), 4493-4502. https://doi.org/10.1093/emboj/19.17.4493
- Benham, A., Grommé, M., & Neefjes, J. (1998). Allelic differences in the relationship between proteasome activity and MHC class I peptide loading. The Journal of Immunology, 161(1), 83-89
- Benham, A., Tulp, A., & Neefjes, J. (1995). Synthesis and assembly of MHC-peptide complexes. Immunology today (Amsterdam. Regular ed.), 16(7), 359-362. https://doi.org/10.1016/0167-5699%2895%2980157-x