Dr Adam Benham, BA (Oxon), PhD
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. My laboratory is particularly 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 (see for example http://www.itv.com/news/tyne-tees/2012-05-01/scientists-discover-fertility-gene/). 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 or 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 are working with Scancell, Notingham and Liverpool University 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 clinical colleagues at 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.
Along with my research commitments, I am Postgraduate Director for the Department of Biosciences, lead the ACAS Departmental research grouping, am module co-ordinator for undergraduate Level 2 Immune Systems and contribute to Biology of Disease 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 committee for the Society for Experimental Biology (Cell section). I have been appointed as an external examiner for various undergraduate degree courses, most recently for the Cardiff University School of Biosciences undergraduate degree schemes (Biomolecular).
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.
- Federal University of São Paulo, Brazil
- Osaka University, Japan
- Procter & Gamble, Cincinnati, US
- Animal Cells and Systems
- Antigen processing and presentation
- Cell biology and biochemistry
- Oxidative folding of proteins in the Endoplasmic Reticulum
- 1: Worfolk, JC, Bell, S, Simpson, LD, Carne, NA, Francis, SL, Engelbertsen, V, Brown, AP, Walker, J, Viswanath, YK & Benham, AM (2019). Elucidation of the AGR2 interactome in esophageal adenocarcinoma cells identifies a redox sensitive chaperone hub for the quality control of MUC-5AC. Antioxidants & Redox Signaling 31(15): 1117-1132.
- 2: Carne, NA, Bell, S, Brown, AP , Maatta, A, Flagler MJ & Benham AM (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.
- 3: Benham, Adam M. (2019). Endoplasmic Reticulum redox pathways: in sickness and in health. The FEBS Journal 286(221): 311-321.
- 4: Schorr-Lenz, A., Alves, J., Hence, N.A., Seidel, P.M., Benham, A.M. & Bustamante-Filho, I.C. (2016). GnRH immunization alters the expression and distribution of protein disulfide isomerases in the epididymis. Andrology 4(5): 957-963.
- 5: Tokuhiro, K., Satouh, Y., Nozawa, K., Isotani, A., Fujihara, Y., Hirashima, Y., Matsumura, H., Takumi, K., Miyano, T., Okabe, M., Benham, A.M. & Ikawa, M. (2015). Calreticulin is required for development of the cumulus oocyte complex and female fertility. Scientific Reports 5: 14254.
- 6: Tarran, W. A., Freeman, G. R., Murphy, L., Benham, A. M., Kataky, R. & Williams, J. A. G. (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.
- 7: Battle, D.M., Dias-Gunasekara, S., Watson, G.R. , Mohamed Ahmed, E., Saysell, C.G., Altaf, N., Sanusi, A.L., Munipalle, P., Scoones, D., Walker, J., Viswanath, Y. & Benham, A.M. (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.
- 8: Benham, A.M., 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): 20110403.
- 9: Tokuhiro, K., Ikawa, M., Benham, AM. & 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 of the United States of America 109(10): 3850-3855.
- 10: Benham, A.M (2012). Protein secretion and the endoplasmic reticulum. In Protein Synthesis and Translational Control. Hershey, JWB, Sonenberg, N & Mathews, MB Cold Spring Harbor Press. 4: 147-162.
- 11: Benham, A.M. (2012). The protein disulfide isomerase family: key players in health and disease. Antioxidants & Redox Signaling 16(8): 781-789.
- 12: Ikawa, M., Tokuhiro, K., Yamaguchi, R., Benham, AM., 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.
- 13: Pekovic, V., Gibbs-Seymour, I.D., Markiewicz, E., Alzoghaibi, F., Benham, A.M., Edwards, R., Wehnert, M., von Zlignicki, T. & Hutchison, C.J. (2011). Conserved cysteine residues in the mammalian lamin A tail are essential for cellular responses to ROS generation. Aging Cell 10(6): 1067-1079.
- 14: van Lith, M., McEwen-Smith, RM. & Benham, AM. (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.
- 15: Ikawa, M., Inoue, N., Benham, A.M. & Okabe, M. (2010). Fertilization: a sperm's journey to and interaction with the oocyte. Journal Clinical Investigation 120(4): 984-994.
- 16: Benham, A.M. (2009). Protein folding and disulfide bond formation in the eukaryotic cell. FEBS Journal 276(23): 6905-11.
- 17: van Lith, M., Karala, A., Bown, D., Gatehouse, J., Ruddock, L., Saunders, P & Benham, AM. (2007). A developmentally regulated chaperone complex for the endoplasmic reticulum of male haploid germ cells. Molecular Biology of the Cell 18(8): 2795-2804.
- 18: Lemin, A., Saleki, K., van Lith, M. & Benham, A.M. (2007). Activation of the unfolded protein response and alternative splicing of ATF6α in HLA-B27 positive lymphocytes. FEBS Letters 581(9): 1819-1824.
- 19: Dias-Gunasekara, S., van Lith, M., Williams, J.A.G., Kataky, R. & Benham, A.M. (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.
- 20: Saleki, K., Hartigan, N., van Lith, M., Bulleid, N. & Benham, A.M. (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.
- 21: van Lith, M. & Benham, A.M. (2006). The DMalpha and DMbeta chain co-operate in the oxidation and folding of HLA-DM. Journal of Immunology 177(8): 5430-5439.
- 22: van Lith M, Hartigan N, Hatch J & Benham AM (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.
- 23: Dias-Gunasekara S, Gubbens J, van Lith M, Dunne C, Williams JA, Kataky R, Scoones D, Lapthorn A, Bulleid NJ & Benham AM (2005). Tissue-specific expression and dimerization of the endoplasmic reticulum oxidoreductase Erolb. Journal of Biological Chemistry 280(38): 33066-33075.
- 24: Dixon, DP., van Lith, M., Edwards, R. & Benham, A.M. (2003). Cloning and initial characterization of the Arabidopsis thaliana Endoplasmic Reticulum Oxidoreductins. Antioxidants and Redox Signaling 5(4): 389-396.
- 25: Mezghrani, A., Fassio, A., Benham, A.M., Simmen, T., Braakman, I. & Sitia, R. (2001). Manipulation of oxidative protein folding and PDI redox state in mammalian cells. EMBO Journal 20(22): 6288-6296.
- 26: Benham, A.M., Cabibbo, A., Fassio, A., Bulleid, N., Sitia, R. & Braakman, I. (2000). The CXXCXXC motif determines the folding, structure and stability of human Ero1-La. EMBO Journal 19(17): 4493-4502.
- 27: Benham, A.M., Grommé, M. & Neefjes, J. (1998). Allelic differences in the relationship between proteasome activity and MHC class I peptide loading. Journal of Immunology 161(1): 83-89.
- 28: Benham, A., Tulp, A. & Neefjes, J. (1995). Synthesis and assembly of MHC-peptide complexes. Immunology Today 16(7): 359-362.