Dr Simon Afford PhD, FRCPath

Dr Simon Afford

Institute of Immunology and Immunotherapy
Reader in Liver Immunopathology
Head of the Birmingham Machine Perfusion Research Group

Contact details

Address
Center for Liver Research
Institute of Immunology and Immunotherapy
Institute of Biomedical Research
University of Birmingham
Edgbaston
Birmingham
B15 2TT
UK

Simon Afford holds a Readership in Liver Immunopathology within the Institute of Immunology and Immunotherapy. He is Scientific Lead of the Birmingham Machine Perfusion Research Group, and Senior Academic Tutor.

Simon has published extensively in scientific journals as well as reviews and book chapters in the fields of cellular and molecular mechanisms of hepatic inflammation. He has received major grants from the Wellcome Trust, Medical Research Council, Biological and Biological Science Research Council and NIHR Birmingham Liver Biomedical Research Unit. He is also actively engaged with industry and has a number of substantive funded research projects. He sits on the editorial board of several prestigious international journals and he has served on many national and international scientific advisory boards and international meeting organising committees.

He is an enthusiastic communicator on his specialist research theme at national and international scientific and biomedical research meetings as well as to various lay groups in the broader community.

Qualifications

  • Fellow of Royal College of Pathologists, 2008
  • Member of the Royal College of Pathologists, 2000
  • PhD in Immunology, University of Birmingham, 1988
  • C Biol. MI Biol. Institute of Biology, 1984
  • Fellow of the Institute of Medical laboratory Sciences, 1983

Biography

Simon studied for a PhD in Immunology and subsequently obtained a personal career development award from the Chest Heart and Stroke Foundation. He then joined the Department of Medicine and the Liver Research Laboratories as a post doctoral fellow continuing to work in Birmingham. In recognition of his published contributions to the field of liver immunopathology, he was awarded an honorary MRC Path in 2000 his Readership in 2006 and FRC Path in 2008.

Teaching

Postgraduate supervision

Simon is interested in supervising doctoral research students in the following areas:

  • The role of TNF/TNFR family members in the development of chronic inflammatory and malignant liver disease.
  • Enhancement of the liver cancer patients immune system.
  • The effects of oxidative stress on liver epithelial cell biology.
  • The use of whole liver normothermic machine perfusion for assessment of donor liver viability, and preclinical studies of targeting of cellular and small molecule therapeutics.

If you are interesting in studying any of these subject areas please contact Simon on the contact details above, or for any general doctoral research enquiries, please email: dr@contacts.bham.ac.uk or call +44 (0)121 414 5005.

For a full list of available Doctoral Research opportunities, please visit our Doctoral Research programme listings   

Research

Research theme

Chronic Inflammatory Liver Disease, Cancer Cell Biology, Clinical Trials, Tumour Immunology and Immune/Gene Therapy, Regenerative Medicine. 

Research activity

Chronic inflammation which fails to resolve is a characteristic feature of many life threatening liver diseases including primary biliary cirrhosis, primary sclerosing cholangitis, hepatitis, alcoholic liver disease, liver allograft rejection and liver cancer. Severe inflammation can lead to permanent tissue damage including fibrosis, loss of organ function and in some cases malignant disease including hepatocellular and cholangiocarcinoma. Simon's group focuses predominantly on the cell and molecular mechanisms which control primary liver cell survival including the intracellular signalling pathways which direct cholagiocyte and hepatocyte survival, apoptosis, autophagy, and cellular transition.

Their access to human liver tissue via the clinical transplant program enables us to carry out detailed molecular and cell biological studies on isolated characterised populations of primary liver cells including epithelium (hepatocytes and cholangiocytes), intrahepatic endothelium, liver derived tumour and inflammatory cells. A better understanding of the pathways which regulate hepatic inflammation is a crucial step which offers the potential to identify new molecular targets and design more specific and effective therapeutic treatments for chronic inflammatory liver disease.

His group has extensive expertise in primary human liver cell isolation and culture and associated immunobiochemical technologies for molecular analysis of cell phenotype and function.

A major focus of their basic molecular research has been determine how activation of tumour necrosis factor receptor (TNFr) superfamily members, particularly CD40 and Fas regulate cell function and survival during inflammation. Most widely known as a costimulatory molecule, CD40 is critical for several aspects of T cell B cell interactions. CD40 is also widely expressed on non haematopoietic cells in the liver where its function is different. Simon's group has shown that CD40 is upregulated in inflammatory liver disease on liver epithelium (hepatocytes and cholangiocytes) and endothelium. It may well have roles in modulation of leukocyte recruitment via endothelium. It also has a profound effect on epithelial cell survival and endothelial cell proliferation.

As a major priority, we are pursuing studies designed to test the hypothesis that TNFR family members including CD40, Fn14, and ROS mediated mechanisms contribute to a tissue microenvironment which promotes chronic inflammation and development of liver pathobiology.

We are also pushing forward rapidly with the NIHR BRU initiative which involves targeting the CD40 system with novel therapeutic agents to stimulate antitumour immune responses in patients with hepatocellular and cholangiocarcinoma. To date this programme has identified and patented a novel biomarker of disease progression in primary sclerosing cholangitis. A recent MRC project grant award has enabled the establishment of a major collaboration between the UoB (Afford and Jarayaman groups), University of Bristol (The Gaston group) and The University of Thailand to investigate the role of a transcription factor PRH in development of Cholangiocarcinoma.

We have over the last two years established a major collaboration with the clinical transplant team to evaluate and develop Normothermic Machine Liver Perfusion (NMLP) for resuscitation of donor organs deemed not to to meet current criteria for transplantation and for a number of further translational research projects. This work has led to the first in man clinical transplant of a marginal donor liver and a major Wellcome Trust Funded clinical Trial.

Other activities

  • Editorial Board Membership
  • J.Hepatology
  • Transplantation
  • Liver Transplantation
  • PLoS One
  • World Journal of Gastroenterology
  • Frontiers in BioScience.
  • CNRS and INSERM International Review Panel for Post Doctoral Career Development Award Programme.
  • NIHR BRU – present theme lead and strategy board member for Liver Cancer Immunotherapy.
  • MRC UK PBC Consortium – key researcher.    

Publications

Recent publications

Article

Kitchen, P, Lee, KY, Clark, DJ, Lau, N, Lertsuwan, J, Sawasdichai, A, Satayavivad, J, Oltean, S, Afford, S, Gaston, K & Jayaraman, P-S 2020, 'A Runaway PRH/HHEX-Notch3-Positive Feedback Loop Drives Cholangiocarcinoma and Determines Response to CDK4/6 Inhibition', Cancer Research, vol. 80, no. 4, pp. 757-770. https://doi.org/10.1158/0008-5472.CAN-19-0942

Laing, RW, Stubblefield, S, Wallace, L, Roobrouck, VD, Bhogal, RH, Schlegel, A, Boteon, YL, Reynolds, GM, Ting, AE, Mirza, DF, Newsome, PN, Mergental, H & Afford, SC 2020, 'The Delivery of Multipotent Adult Progenitor Cells to Extended Criteria Human Donor Livers Using Normothermic Machine Perfusion', Frontiers in immunology, vol. 11, 1226. https://doi.org/10.3389/fimmu.2020.01226

Mergental, H, Laing, RW, Kirkham, AJ, Perera, MTPR, Boteon, YL, Attard, J, Barton, D, Curbishley, S, Wilkhu, M, Neil, DAH, Hübscher, SG, Muiesan, P, Isaac, JR, Roberts, KJ, Abradelo, M, Schlegel, A, Ferguson, J, Cilliers, H, Bion, J, Adams, DH, Morris, C, Friend, PJ, Yap, C, Afford, SC & Mirza, DF 2020, 'Transplantation of discarded livers following viability testing with normothermic machine perfusion', Nature Communications, vol. 11, no. 1, 2939. https://doi.org/10.1038/s41467-020-16251-3

Boteon, YL, Attard, J, Boteon, APCS, Wallace, L, Reynolds, G, Hubscher, S, Mirza, DF, Mergental, H, Bhogal, RH & Afford, SC 2019, 'Manipulation of Lipid Metabolism During Normothermic Machine Perfusion: Effect of Defatting Therapies on Donor Liver Functional Recovery', Liver Transplantation, vol. 25, no. 7, pp. 1007-1022. https://doi.org/10.1002/lt.25439

Boteon, YL, Laing, RW, Schlegel, A, Wallace, L, Smith, A, Attard, J, Bhogal, RH, Reynolds, G, Pr Perera, MT, Muiesan, P, Mirza, DF, Mergental, H & Afford, SC 2019, 'The impact on the bioenergetic status and oxidative-mediated tissue injury of a combined protocol of hypothermic and normothermic machine perfusion using an acellular haemoglobin-based oxygen carrier: The cold-to-warm machine perfusion of the liver', PLoS ONE, vol. 14, no. 10, e0224066. https://doi.org/10.1371/journal.pone.0224066

Longatto Boteon, Y, Wallace, L, Pinter Carvalheiro da Silva Boteon, A, Mirza, D, Mergentel, H, Bhogal, R & Afford, S 2018, 'An effective protocol for Pharmacological Defatting of Primary Human Hepatocytes which is non-toxic to Cholangiocytes or Intrahepatic endothelial cells', PLoS ONE, vol. 13, no. 7, e0201419. https://doi.org/10.1371/journal.pone.0201419

Lertsuwan, J, Lertsuwan, K, Sawasdichai, A, Tasnawijitwong, N, Lee, KY, Kitchen, P, Afford, S, Gaston, K, Jayaraman, P-S & Satayavivad, J 2018, 'CX-4945 Induces Methuosis in Cholangiocarcinoma Cell Lines by a CK2-Independent Mechanism', Cancers, vol. 10, no. 9, 283. https://doi.org/10.3390/cancers10090283

Boteon, YL, Laing, RW, Schlegel, A, Wallace, L, Smith, A, Attard, J, Bhogal, RH, Neil, DAH, Hübscher, S, Perera, MTPR, Mirza, DF, Afford, SC & Mergental, H 2018, 'Combined Hypothermic and Normothermic Machine Perfusion Improves Functional Recovery of Extended Criteria Donor Livers', Liver Transplantation, vol. 24, no. 12, pp. 1699-1715. https://doi.org/10.1002/lt.25315

Mergental, H, Stephenson, BTF, Laing, RW, Kirkham, AJ, Neil, DAH, Wallace, LL, Boteon, YL, Widmer, J, Bhogal, RH, Perera, MTPR, Smith, A, Reynolds, GM, Yap, C, Hübscher, SG, Mirza, DF & Afford, SC 2018, 'Development of Clinical Criteria for Functional Assessment to Predict Primary Nonfunction of High-Risk Livers Using Normothermic Machine Perfusion', Liver Transplantation, vol. 24, no. 10, pp. 1453-1469. https://doi.org/10.1002/lt.25291

Stephenson, B, Bonney, G, Laing, R, Bhogal, R, Marcon, F, Neil, D, Perera, MTPR, Afford, S, Mergental, H & Mirza, DF 2018, 'Proof of concept: liver splitting during normothermic machine perfusion', Journal of Surgical Case Reports, vol. 3, pp. 1-6. https://doi.org/10.1093/jscr/rjx218

Bhogal, R, Weston, C, Velduis, S, Henri GD, L, Reynolds, G, Davies, S, Luu, N-T, Alfaifi, M, Shepherd, E, Boteon, Y, Wallace, L, Oo, YH, Adams, D, Mirza, DF, Mergentel, H, Muirhead, G, Stephenson, B & Afford, S 2018, 'The ROS-Mitophagy Signalling Pathway regulates liver endothelial cell survival during ischaemia-reperfusion injury', Liver Transplantation. https://doi.org/10.1002/lt.25313

Longatto Boteon, Y, Laing, R, Mergental, H, Reynolds, G, Mirza, D, Afford, S & Bhogal, R 2017, 'Mechanisms of autophagy activation in endothelial cell and their targeting during normothermic machine liver perfusion', World Journal of Gastroenterology, vol. 23, no. 48, pp. 8443-8451.

Laing, RW, Bhogal, RH, Wallace, L, Boteon, Y, Neil, DAH, Smith, A, Stephenson, BTF, Schlegel, A, Hübscher, SG, Mirza, DF, Afford, SC, Mergental, H & Hubscher, S 2017, 'The Use of an Acellular Oxygen Carrier in a Human Liver Model of Normothermic Machine Perfusion', Transplantation, vol. 101, no. 11, pp. 2746-2756. https://doi.org/10.1097/TP.0000000000001821

Laing, RW, Mergental, H, Yap, C, Kirkham, A, Whilku, M, Barton, D, Curbishley, S, Boteon, YL, Neil, DA, Hübscher, SG, Perera, MTPR, Muiesan, P, Isaac, J, Roberts, KJ, Cilliers, H, Afford, SC & Mirza, DF 2017, 'Viability testing and transplantation of marginal livers (VITTAL) using normothermic machine perfusion: study protocol for an open-label, non-randomised, prospective, single-arm trial', BMJ open, vol. 7, no. 11, e017733. https://doi.org/10.1136/bmjopen-2017-017733

Review article

Boteon, YL, Afford, S & Mergental, H 2018, 'Pushing the Limits: Machine Preservation of the Liver as a Tool to Recondition High-Risk Grafts', Current Transplantation Reports, vol. 5, no. 2, pp. 113-120. https://doi.org/10.1007/s40472-018-0188-7

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