Dr Daniel Hodson
Position: Clinical Consultant
Personal home page: http://www.haem.cam.ac.uk/staff/senior-staff/dr-daniel-hodson/
PubMed journal articles - click here
Dr Daniel Hodson is pleased to consider applications from prospective PhD students.
Pathogenesis of Germinal Centre Derived B Cell Lymphomas. Many of the commonest human lymphomas (including follicular, diffuse large B cell and Burkitt lymphomas) develop from a specific stage of B lymphocyte differentiation termed the Germinal Centre. Normal B lymphocytes form part of our adaptive immune system. B cells encountering a foreign antigen in the context of T cell help initiate the formation of transient microanatomical structures termed germinal centres. Within germinal centres B cells undergo multiple rounds of intense proliferation coupled with somatic hypermutation of the immunoglobulin genes that alter the affinity for antigen. Those with greater affinity for antigen successfully compete for T cell help before exiting the germinal centre as immunoglobulin secreting plasma cells or memory B cells, whereas less competitive B cells default to apoptosis. Rapidly changing, but tightly controlled, programmes of gene expression determine successive cell fate choices during the germinal centre reaction. It is the loss of this tight control and the resulting corruption of cell fate choices within the germinal centre that results in the development of malignant lymphoma and that forms the focus of my group?s research. The networks of transcription factors that regulate the germinal centre reaction have been well characterised in recent years. Their importance is underscored by the finding of recurrent somatic mutation in these transcriptional regulators in next generation sequencing studies of GC derived lymphomas. It has recently become clear that a major tier of regulation is also imposed in a highly dynamic fashion at the level of translation. Importantly, translation control is invisible to conventional gene expression profiling techniques such as microarray or RNA-seq and so the contribution of translational regulation to the control of either normal or malignant gene expression remains poorly studied. A particular focus of our group is the use of transcriptome wide translational profiling to understand how normal gene expression becomes corrupted at the level of translation during the development of lymphoma. Furthermore, we wish to reveal how this corruption of translation is brought about by somatic mutation of RNA-binding proteins that control translation (translation factors) and by the activation of oncogenic signalling pathways that regulate the activity of these translation factors. Finally we wish to characterise how new therapeutic agents that are entering trials for lymphoma may exert some of their effect though changes in translation and conversely how resistance to these agents may arise by feedback mechanisms acting at the level of mRNA translation.
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Galloway A, Saveliev A, Lukasiak S, Hodson DJ, Bolland D, Ahlfors H, Monzón-Casanova E, Ciullini Mannurita S, Bell LS, Andrews S, Díaz-Muñoz MD, Corcoran A, and Turner M. RNA binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence. Science 2016; 352 (6284):453-9
Hodson DJ, Shaffer AL, Xiao W, Wright GW, Schmitz R, Phelan JD, Yang Y, Webster DE, Rui L, Kohlhammer H, Nakagawa M, Waldmann TA, Staudt LM. Regulation of normal B-cell differentiation and malignant B-cell survival by OCT2. Proc Natl Acad Sci U S A. 2016 Mar 18.
Schmitz R, Young RM, Ceribelli M, Jhavar S, Xiao W, Zhang M, Wright G, Shaffer A, Hodson DJ, Buras E, Liu X, Powell J, Yang Y, Xu W, Zhao H, Kohlhammer H, Rosenwald A, Kluin P, Müller-Hermelink HK, Ott G, Gascoyne RD, Connors JC, Rimsza LM, Campo E, Jaffe E, Delabie J, Smeland EB, Ogwang MD, Reynolds SJ, Fisher RI, Braziel RM, Tubbs RR, Cook JR, Weisenburger DD, Chan WC, Pittaluga S, Wilson W, Waldmann TA, Rowe M, Mbulaiteye SM, Rickinson AB, and Staudt LM. Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics. Nature 2012; 490:116-120
Turner M, Hodson DJ. An emerging role of RNA-binding proteins as multifunctional regulators of lymphocyte development and function. Immunology Reviews 2012 May; (115):161-185.
Turner M, Hodson D. Regulation of lymphocyte development and function by RNA-binding proteins. Curr Opin Immunol 2012 Apr; 24(2):160-5.
Hodson DJ, Janas ML, Galloway A, Bell SE, Andrews S, Li CM, Pannell RP, Siebel CW, MacDonald HR, De Keersmaecker K, Adolfo A, Ferrando AA, Grutz G and Martin Turner M. Deletion of the RNA-binding proteins Zfp36l1 and Zfp36l2 leads to perturbed thymic development and T-lymphoblastic leukaemia. Nature Immunology 2010 Aug; 11(8):717-24.
Gururajan M, Haga CL, Das S, Leu CM, Hodson D, Josson S, Turner M, Cooper MD. MicroRNA 125b inhibition of B cell differentiation in germinal centers. Int Immunol Jul; 22(7):583-92.
Hodson DJ, Turner M. The role of PI3K signaling in the B cell response to antigen. Adv Exp Med Biol 2009; 633:43-53.
Hussain N, Hodson D, Marcus R, Baglin T, Luddington R. The biphasic transmittance waveform: an early marker of sepsis in patients with neutropenia. Thromb Haemost 2008 Jul; 100(1):146-8.
Janas ML, Hodson D, Stamataki Z, Hill S, Welch K, Gambardella L, Trotman LC, Pandolfi PP, Vigorito E, Turner M. The effect of deleting p110delta on the phenotype and function of PTEN deficient B cells. Journal of Immunology 2008 Jan 15; 180(2):739-46.
Hodson DJ, Bowles KM, Cooke LJ, Kläger SL, Powell GA, Laing RJ, Grant JW, Williams MV, Burnet NG, Marcus RE. Primary Central Nervous System Lymphoma (PCNSL): A single centre experience of 55 unselected cases. Clinical Oncology 2005; 17(3):185–191.