Dr Eksteen is a MRC Clinician Scientist and PI in the MRC Centre for Immune Regulation and the NIHR Biomedical Liver Research Unit at the University of Birmingham. His research and clinical interests are focused on chronic inflammatory liver diseases such as Primary Sclerosing Cholangitis (PSC) and the immune processes that underpin them. At present Dr Eksteen hold a joint appointment with the University of Birmingham and the University of Calgary to advance research into PSC. Dr Eksteen has held major research grants from the MRC, Wellcome Trust, CORE charity and the British Liver Foundation.
His work has acknowledged by several awards including the the Medical Research Society/Academy of Medical Sciences/RCP Young Investigators Award, Royal College of Physicians in 2006, the Dame Sheila Sherlock Research prize from the British Association for the Study of the Liver (BASL) in 2007 and in 2010 the Sir Francis Avery Jones Research Medal from the British Society of Gastroenterology. He is the 2011 Association of National European and Mediterranean Societies of Gastroenterology (ASNEMGE) rising Star recipient.
Certificate of completion of specialist training (CCT) in Gastroenterology and Internal Medicine 2009 - Postgraduate Medical and Training Board, UK
PhD Medicine – 2007 University of Birmingham
Membership of the Royal College of Physicians (MRCP) 1999
MBChB 1996 University of Pretoria
Dr Eksteen graduated from the medical school at the University of Pretoria in South Africa before moving to the Liver Unit in Birmingham, UK to pursue his training in clinical hepatology and research into autoimmune liver disease. He obtained a PhD in 2007 and was awarded a prestigious MRC Clinician Scientist Fellowship in 2008. He is a PI in the MRC Centre for Immune Regulation and an honorary consultant hepatologist at the Queen Elizabeth Hospital Birmingham. His research program extends to the University of Calgary where he holds a joint appointment.
He has pioneered studies into the pathogenesis of Primary sclerosing cholangitis (PSC). PSC is an auto-immune liver disease that occurs as an extra-intestinal manifestation of inflammatory bowel disease (IBD). To explain this link between the gut and the liver, he proposed the existence of an entero-hepatic pathway of lymphocyte trafficking in which lymphocytes activated in the gut migrate to the liver and contribute to liver inflammation. In support of this hypothesis, he was the first to show that ectopic expression of the gut restricted chemokine, CCL25 outside of the gut and the presence mucosal CCR9+ α4β7+ T cells in the PSC liver. . Eksteen B et al. J Exp Med 2004. Eksteen B et al. J Immunol 2006. Adams DH, Eksteen B. Nat Rev Immunol 2006. Eksteen B et al. Gastroenterology 2009.
In order to define how mucosal homing lymphocytes are generated and adaptive immune responses are targeted to the gut he initiated collaborations with Dr Mora and Prof von Andrian in Harvard and Prof Agace in Sweden and were able to show that expression of gut homing receptors are retinoic acid dependent and only imprinted on T and IgA secreting B cells during activation by specific CD103+ dendritic cells (DC) in the gut. Mora, Iwata M, Eksteen B et al. Science 2006. Jaensson E et al. J Exp Med 2008.
Having defined the molecules that control entero-hepatic lymphocyte trafficking and the central role of retinoic acid, I reported the how regulatory T cells are recruited to the liver and exploited this knowledge by setting up a phase 1 clinical trial in Birmingham in patients with PSC and IBD that uses autologous gut tropic regulatory T cells and aims to reduce hepatic inflammation. Eksteen B et al. J Immunol 2006. Oo YH et al. J Immunol. 2010.
His work has been acknowledged by some of the most prestigious research awards in the UK. They include the Medical Research Society/Academy of Medical Sciences/RCP Young Investigators Award, Royal College of Physicians in 2006, the Dame Sheila Sherlock Research prize from the British Association for the Study of the Liver (BASL) in 2007 and in 2010 the Sir Francis Avery Jones Research Medal from the British Society of Gastroenterology. He is the 2011 Association of National European and Mediterranean Societies of Gastroenterology (ASNEMGE) rising Star recipient.
Immunology module (MBChB year 2)
Liver and Immunology modules (MSc)
Liver module (BMedSci)
Areas of research
Mechanisms that regulate adaptive immune responses in the liver and the gut.
Regulation of entero-hepatic lymphocyte recruitment.
Experimental models of hepatitis and gut inflammation
Translational studies in man in Inflammatory Bowel Disease and Primary Sclerosing Cholangitis.
CLINICAL ACTIVITY / NHS AFFILIATION
Honorary Consultant Hepatologist – Liver Transplant Unit, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust.
- Clinical interests: Primary Sclerosing Cholangitis, Liver Transplantation, Phase 1/2 clinical studies
- Joint research programme at the snyder institute of immunology, infection and inflammation at the university of calgary, calgary, canada.
- Imaging of immune cells in the liver, models of liver disease.
Eksteen B, Mora JR, Haughton EL et al. Gut homing receptors on CD8 T-cells ARE retinoic acid dependent and not maintained by Liver dendritic or stellate cells. Gastroenterology 2009.
Miles A, Liaskou E, Eksteen B, Lalor PF, Adams DH. CCL25 and CCL28 promote alpha4 beta7-integrin-dependent adhesion of lymphocytes to MAdCAM-1 under shear flow. Am J Physiol Gastrointest Liver Physiol 2008;294(5):G1257-G1267.
Jaensson E, Uronen-Hansson H, Pabst O et al. Small intestinal CD103 dendritic cells display unique functional properties that are conserved between mice and humans. J Exp Med 2008;205(9):2139-2149.
Adams DH, Eksteen B. Aberrant homing of mucosal T cells and extra-intestinal manifestations of inflammatory bowel disease. Nat Rev Immunol 2006;6(3):244-251.
Eksteen B, Miles A, Curbishley SM et al. Epithelial Inflammation Is Associated with CCL28 Production and the Recruitment of Regulatory T Cells Expressing CCR10. J Immunol 2006;177(1):593-603.
Mora JR, Iwata M, Eksteen B et al. Generation of gut-homing IgA-secreting B cells by intestinal dendritic cells. Science 2006;314(5802):1157-1160.
Curbishley SM, Eksteen B, Gladue RP, Lalor P, Adams DH. CXCR3 Activation Promotes Lymphocyte Transendothelial Migration across Human Hepatic Endothelium under Fluid Flow. Am J Pathol 2005;167(3):887-899.
Eksteen B, Grant AJ, Miles A et al. Hepatic endothelial CCL25 mediates the recruitment of CCR9 gut-homing lymphocytes to the liver in primary sclerosing cholangitis. J Exp Med 2004;200(11):1511-7.