Head of Department and Professor of Leukaemia Stem Cell Biology
Research themes:Stem Cell, Cancer
Description of research
Leukaemias have recently been demonstrated to be wholly dependent upon a small population of so-called cancer stem cells. These cells represent the critical targets for treatment and a greater understanding of their biology and its interface with normal stem cell function is fundamental to improving treatment outcomes.
The focus of the Huntly laboratory is on this interface. We use a combination of techniques in cell line and animal models as well as confirmatory studies in primary human tissue to dissect stem cell function. Our aim is to understand how normal stem cell function is subverted in cancer and how these processes might be therapeutically targeted to improve the outcome in haematological malignancies. We are examining the role of mutations that occur in and alter the role of haematopoietic stem and progenitors as early events before leading to the subsequent development of leukaemias and lymphomas (pre-leukaemic stem cells). Many of these mutations alter epigenetic regulation, enhancer function and transcriptional programmes and these are all ongoing areas of investigation within the lab.
Therapeutically, a recent example of our work is the identification of the Bromodomain and extra terminal (BET) proteins as critical mediators of leukaemia stem cells in acute myeloid leukaemia and the development of an inhibitor of these proteins that has already entered early phase clinical trials in relapsed blood cancers.
Keywords: Leukaemogenesis, leukaemia stem cell, haematopoietic stem cell, epigenetic regulators, translation factors, CBP, SOX4, BET
Clinical conditions: Leukaemia, acute myeloid leukaemia, chronic myeloid leukaemia
Methodologies: Functional assays, genomic assays, complementary mouse models, human primary cells