Professor Brian Huntly
Leukaemia stem cell biology and leukaemogenesis
Cambridge Institute for Medical Research, Cambridge Biomedical Campus
Prof Brian Huntly is a clinical academic who combines running a laboratory group with his practice as a Consultant Haematologist in Addenbrooke’s Hospital. He studied Medicine at Edinburgh, trained in Haematology in Dundee and Cambridge and is a member of the Royal College of Physicians and a Fellow of the Royal College of Pathologists. He studied for his PhD in Cambridge and performed post-doctoral work at Harvad, prior to returning to Cambridge to set up his own research group.
European Research Council, Kay Kendall Leukaemia Fund, Worldwide Cancer Research, Leukaemia Lymphoma Research Programme, Medical Research Council
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 AML and the development of an inhibitor of these proteins that has already entered early phase clinical trials in relapsed blood cancers.
Ann Sopihie Bach
Our group are interested in the interface between normal and malignant haematopoietic stem cell biology. Comparisons of these systems will allow us to determine how normal regulatory mechanisms are corrupted to generate haematological malignancies. We use experimental model systems and patient sample to answer these questions. This information will provide the basis for targeted therapies to improve the dismal treatment outcomes for haematological cancers.
- Giotopoulos G, Van der Weyden L, Osaki H, Rust A, Meduri E, Chan WI, Paul D, Horton SJ, Gallipoli P, Pimanda JE, Prinjha R, Tenen DG, Vassiliou GS, Koschmieder S, Adams DJ, Huntly BJP. A novel murine model identifies cooperating mutations and therapeutic targets critical for the progression of chronic myeloid leukemia (CML). J Exp Med.2015 Aug 24. pii: jem.20141661. PMCID:PMC4577832
- Dawson MA, Prinjha RK, Dittmann A, Giotopoulos G, Bantscheff M, Chan WI, Robson SC, Chung CW, Hopf C, Savitski MM, Huthmacher C, Gudgin E, Lugo D, Beinke S, Chapman TD, Roberts EJ, Soden PE, Auger KR, Mirguet O, Doehner K, Delwel R, Burnett AK, Jeffrey P, Drewes G, Lee K, Huntly BJ*, Kouzarides T*. Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. Nature. 2011 478(7370):529-33 *joint senior authors PMCID:PMC3679520
- Anand S, Stedham FE, Beer PA, Gudgin E, Bench AJ, Green AR, Huntly BJP. Increased basal intracellular signaling patterns do not correlate with JAK2 genotype in human myeloproliferative neoplasms. Blood. 2011 Aug 11;118(6):1610-21. PMID:21653937
- Bansal D, Scholl C, Frohling S, McDowell E, Lee BH, Dohner K, Ernst P, Davidson A, Daley GQ, Zon LI, Gilliland DG, Huntly BJP. Cdx4 upregulates Hox gene expression and generates acute myeloid leukemia alone and in cooperation with Meis1a in a murine model. Proc Natl Acad Sci U S A. 2006 103:16924-9. PMCID:PMC1636555
- Huntly BJP, Shigematzu H, Deguchi K, Lee BH, Mizuno S, Duclos N, Rowan R, Amaral S, Curley D, Williams IR, Akashi K, Gilliland DG. MOZ-TIF2, but not BCR-ABL, confers properties of leukaemic stem cells to committed murine haematopoietic progenitors. Cancer Cell. 2004; 6: 586-595 PMID:15607963