Liver and Blood-Related Cell Therapy

Area Academic Contact: Professor Jon Frampton, Director of Research and Knowledge Transfer, College of Medical and Dental Sciences, j.frampton@bham.ac.uk

Although representing very distinct organ systems, research into diseases affecting the liver and blood is linked through common experimental and clinical approaches, including an understanding of basic stem cell biology, the development of cell-based therapeutic approaches, and transplantation medicine.  

This area incorporates groups from the Research Domains of Genetics & Development, Cancer, and Immunity & Infection.  Prominent centres that attract considerable recognition and income are associated with both of the aligned clinical disciplines, namely the NIHR Liver Biomedical Research Unit (BRU) and the Leukaemia Centre.

Specific Research Themes

Immune regulation in liver disease

  • Understanding the role of specific adhesion molecules and chemokines in the regulation of lymphocyte recruitment to the liver and gut.
  • The role of dendritic cells in regulating local immune responses in the liver
  • Hepatitis virology and immune evasion
  • Primary liver cancer
  • Gene therapy and novel therapeutic interventions in hepatitis and non-hepatitis associated primary liver cancer
  • Immune responses to hepatocellular carcinoma and cholangiocarcinoma and biomarkers for these cancers.
  • Tissue Injury and Transplantation Immunity and cell-mediated injury in the liver.
  • Molecular regulation of ischemia reperfusion and pre-conditioning in the liver.
  • Regulation of inflammation in the liver.

Haematology research

  • Identification of the molecular basis of dysregulated haematopoiesis characterizing myeloid malignancies
  • Developing immunotherapeutic strategies aimed at optimizing a graft-versus-leukaemia effect after allogeneic transplantation
  • Biological and clinical activity of epigenetic therapies in acute myeloid leukaemia and myelodysplasia
  • Integration of target therapies such as imatinib into novel conditioning regimens in allogeneic stem cell transplantation
  • Development of novel therapies in myeloma and chronic lymphocytic leukaemia

Key Investigators

Recent Research Grants 

  • NIHR Biomedical Research Unit, Department of Health
  • Vascular Adhesion Protein-1: A Multi-Functional Enzyme Providing a Link Between Fibrogenesis and Inflammation, Wellcome Trust
  • Pre-Clinical Study of Hepatocyte Transplantation Using Human Embryonic Stem Cell-Derived Hepatocytes, MRC
  • Mesenchymal Stem Cell Homing to the Chronically Injured Liver, MRC
  • Recruitment and Immunomodulatory Effects of Mesenchymal Stem Cells Investigated in Multicellular, in vitro Models of Inflamed Vasculature, British Heart Foundation
  • Stem Cell Sorting Facility, Wellcome Trust
  • Therapy Acceleration Programme, Leukaemia & Lymphoma Research
  • United Kingdom Acute Lymphoblastic Leukaemia Trial 2010 (UKALL2010), Leukaemia & Lymphoma Research
  • A Randomized Phase II Trial CMV Specific Adoptive Immunotherapy After Stem Cell Transplantation”, Leukaemia & Lymphoma Research
  • Study of the Mechanisms Underlying the Graft Versus Leukaemia Effect in Stem Cell Transplantation, Leukaemia & Lymphoma Research
  • ATM Pathways in CLL: The Development of Targeted Treatment, Leukaemia & Lymphoma Research and Kudos Pharmaceuticals

Recent Publications

  • Hay DC, et al (2008) Highly efficient differentiation of hESCs to functional hepatic endoderm requires ActivinA and Wnt3a signaling. Proc Natl Acad Sci, 105: 12301-6.
  • Eksteen B, et al (2009) Gut Homing Receptors on CD8 T Cells Are Retinoic Acid Dependent and Not Maintained by Liver Dendritic or Stellate Cells. Gastroenterol, 137: 320-9.
  • Holt AP, et al (2009) Liver Myofibroblasts Regulate Infiltration and Positioning of Lymphocytes in Human Liver. Gastroenterol, 136: 705-14.
  • Weston VJ, et al (2010). The PARP inhibitor olaparib induces significant killing of ATM-deficient lymphoid tumor cells in vitro and in vivo. Blood, 116: 4578-87.
  • Oo YH, et al (2010) Distinct Roles for CCR4 and CXCR3 in the Recruitment and Positioning of Regulatory T Cells in the Inflamed Human Liver. J Immunol, 184: 2886-98.
  • Morgan GJ, et al (2010) First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet, 376: 1989-99.
  • Goodyear OC, et al (2010) Induction of a CD8(+) T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Blood, 116: 1908-18.
  • Lamprecht B, et al (2010) Derepression of an endogenous long terminal repeat activates the CSF1R proto-oncogene in human lymphoma. Nature Med, 16: 571-9.
  • Dowman JK, et al (2011) Liver transplantation from donors with acute intermittent porphyria. Ann Intern Med, 154: 571-2.
  • Goardon N, et al (2011) Coexistence of LMPP-like and GMP-like Leukemia Stem Cells in Acute Myeloid Leukemia. Cancer Cell, 19: 138-52.