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The research focuses on:
Research includes:
• development of innovative therapy for liver disease, including new surgical techniques;
• use of marginal livers and isolated human hepatocytes to increase the organ pool;
• novel surgical and medical managements of biliary atresia;
• liver gene therapy, cancer therapy by exploiting allogeneic immune recognition;
• supportive management for liver failure, including the liver role in controlling growth hormone/insulin-like growth factor axis;
• insulin resistance in chronic liver disease and acute liver failure; muscle and adrenal dysfunction in critically ill patients;
• influence of cirrhotic cardiomyopathy and intrathoracic volume on renal function and haemodynamic status;
• pathophysiology of cerebral edema;
• impact of defective monocyte function on the outcome of liver failure; extra-corporeal liver support devices;
• immunopathology of liver damage, including immuno pathogenic aspects of autoimmune and viral induced liver disease; rejection and tolerance in liver transplantation
• molecular basis of cholestasis and bile formation, including genetic characterisation of progressive familial intrahepatic cholestasis type 1 (BSEP deficiency), type 2 (PFC1 disease), type 3 (MDR3 deficiency), neonatal sclerosing cholangitis, intestinal microvillus atrophy.
Liver Sciences
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DESCRIPTION
The Institute of Liver Studies mission is to produce research that impacts directly on patient care by perfecting surgical techniques and supportive management of the failing liver and elucidating mechanisms of liver damage to develop specific and more efficient modes of treatment. The research focuses on:
- Hepatocyte Biology: developing hepatocyte transplantation for children with liver-based metabolic disorders
- Liver Immunopathology: investigating immune mechanisms involved in autoimmune hepatitis; primary biliary cirrhosis; viral hepatitis; and acute liver failure
- Liver Molecular Genetics: investigating the molecular basis of cholestasis and bile formation
Research includes:
• development of innovative therapy for liver disease, including new surgical techniques;
• use of marginal livers and isolated human hepatocytes to increase the organ pool;
• novel surgical and medical managements of biliary atresia;
• liver gene therapy, cancer therapy by exploiting allogeneic immune recognition;
• supportive management for liver failure, including the liver role in controlling growth hormone/insulin-like growth factor axis;
• insulin resistance in chronic liver disease and acute liver failure; muscle and adrenal dysfunction in critically ill patients;
• influence of cirrhotic cardiomyopathy and intrathoracic volume on renal function and haemodynamic status;
• pathophysiology of cerebral edema;
• impact of defective monocyte function on the outcome of liver failure; extra-corporeal liver support devices;
• immunopathology of liver damage, including immuno pathogenic aspects of autoimmune and viral induced liver disease; rejection and tolerance in liver transplantation
• molecular basis of cholestasis and bile formation, including genetic characterisation of progressive familial intrahepatic cholestasis type 1 (BSEP deficiency), type 2 (PFC1 disease), type 3 (MDR3 deficiency), neonatal sclerosing cholangitis, intestinal microvillus atrophy.
Associated research programmes
Associated staff research interests
Interests:
Pathogenesis of autoimmune and viral liver disease and of liver transplant rejection/tolerance.
Email:
Website:
Interests:
Bile duct specific autoantigen in primary biliary cirrhosis; role of molecular mimicry
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Interests:
Paediatric hepatology; autoimmune liver disease; liver transplantation; biliary atresia; aplha-1 antitrypsin deficiency.
Tel:
020 3299 4643
Fax:
020 3299 4224
Email:
Website:
Interests:
Gene therapy for single gene disorders of the liver, for type 1 diabetes, and for immunoregulation, especially in transplantation. Development of a new class of peptide nanoparticle for drug delivery
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Interests:
Intensive care; mechanisms of severe liver injury; multi-organ failure - clinical and basic aspects.
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Interests:
Immunotherapy of liver tumours; pathophysiology and immunopathology of viral hepatitis; non-invasive assessment of liver fibrosis
Tel:
020 3299 3369
Fax:
020 3299 3167
Email:
Website:
Interests:
Genetics of cholestatic liver disease
Email:
Website:
Interests:
The Hepatocyte Transplantation & Biology Group is developing hepatocyte transplantation as a treatment for patients with liver disease. There are a number of advantages of cell transplantation over whole organ transplantation. Eight patients with liver-based metabolic defects have received human hepatocytes prepared in our GMP laboratory. The laboratory research is focussed on overcoming the barriers to wider use of hepatocyte transplantation. Currently this includes investigation of methods to improve the quality of hepatocytes isolated from fatty livers, which are often rejected for transplantation. In the future it is hoped that liver stem cells can be used to replace cells isolated from donor liver and this area is being investigated in collaborative studies. Isolated hepatocytes need to be cryopreserved to give good function on thawing, so that they are available for immediate clinical use when needed. Although progress has been made in our laboratory to improve cryopreservation protocols and understand the mechanisms of cryopreservation-induced damage, there is still scope for further improvement. There are also studies on-going to develop methods of cell therapy for patients with acute liver failure and to track cells once they have been administered to the patient.
Tel:
020 3299 3137
Email:
Website:
Interests:
Immune responses and development of cell therapy for tolerance induction in organ transplantation
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Interests:
My main research interests are defining autoantigens in childhood autoimmune liver diseases (AILD), characterising the defects leading to immunotolerance breaks down in AILD, and defining the genetic association with AILD, including HLA and non-HLA immunoregulatory genes. I am also interested in characterising anti-viral immune response. In addition to isolating and identifying new autoantigens (alcohol dehydrogenage and soluble liver antigen) in the past, I have recently defined immunodominant epitopes on one of the major autoantigens, cytochrome P450 2D6 (CYP2D6) for CD4 and CD8 T cells. These epitopes will be used to isolate and expand antigen specific CD4+CD25+ regulatory T cells (T-regs), which are numerically and functionally defected in AILD. The immunoregulatory genes, FOXP3 and LAG3 (in controlling the suppressive function of T-regs) and AIRE (in controlling central immunotolerance) are currently under investigation. The final goal of my research is to facilitate the development of novel immunoregulatory therapies to replace the currently used toxic immunosuppressive treatment for AILD and to boost anti-viral immunity in viral hepatitis.
Tel:
020 3299 4104
Fax:
020 3299 3760
Email:
Website:
CONTACTS FOR FURTHER INFORMATION
Professor Giorgina Mieli-Vergani
Email
Website