Dr Daniel Hodson
Mutation timing in lymphomagenesis
Laboratory: Cambridge Stem Cell Institute, Clifford Albutt Building, Cambridge Biomedical Campus
Departmental Affiliation: Haematology
Dr Hodson studied Medicine at Cambridge University and then clinical medicine at Oxford University. He subsequently trained as a clinical haematologist with a special interest in lymphoid malignancies. During his haematology training he undertook a PhD in molecular immunology at the Babraham Institute in Cambridge under the supervision of Dr Martin Turner, where he studied the contribution of post-transcriptional regulation to the normal lymphocyte development. In 2010 he moved to the National Cancer Institute, USA, as a post-doctoral fellow in the lab of Dr Lou Staudt, where he developed expertise in the application of functional genomics to the study of B cell lymphomas. In 2015 he returned to Cambridge as a Medical Research Council Clinician Scientist and group leader in the SCI and the Department of Haematology. His group researches the molecular mechanisms that underlie lymphomagenesis. Dr Hodson also holds an honorary consultant contract in the Haematology Department at Addenbrooke’s Hospital.
The unique and dangerous life of the B cell
Normal B lymphocytes progress through a series of developmental stages that begin with the haematopoietic stem cell. Progression through each of these stages is tightly controlled at both the transcriptional and post-transcriptional levels. Genetic alterations and mutations, which can occur at any stage from the haematopoietic stem cell to the post-germinal centre B cell, can lead to loss of this normal regulation and subsequently to the development of lymphoid malignancies such as non-Hodgkin Lymphoma (NHL), which is the 6th commonest form of human cancer. Understanding how these genetic alterations corrupt cell fate choices at each stage of lymphocyte development will be the key to identifying cellular pathways that can be therapeutically targeted. My group is developing novel cell culture models to study the effects of these genetic alterations in human lymphocytes. In particular, we are interested to study how these genetic alterations lead to changes at the level of mRNA translation and how these post-transcriptional changes then contribute to lymphomagenesis. We use a variety of techniques including exome and RNA sequencing, ribosome profiling, iCLIP and xenografts to identify the developmental timing of these genetic alterations, their mechanistic contribution to lymphomagenesis and the implications this has for the treatment and monitoring of patients.
Rebecca Caeser, Miriam Di Re, Jane Gao, Jade Gong.
- Galloway A, Saveliev A, Lukasiak S, Hodson DJ ... and Turner M. RNA binding proteins ZFP36L1 and ZFP36L2 promote cell quiescence. Science 2016; 352 (6284):453-9 PMID: 27102483
- 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. PMCID: PMC4833274
- Schmitz R, Young RM, Ceribelli1 M, Jhavar S, Xiao W, Zhang M, Wright G, Shaffer A, Hodson DJ, Buras E, Liu X, Powell J, Yang Y, Xu W, ZhaoH, 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, Staudt LM. Burkitt Lymphoma Pathogenesis and Therapeutic Targets from Structural and Functional Genomics. Nature 2012: 490: 116-120. PMCID:PMC3609867
- Turner M, Hodson DJ. An emerging role of RNA-binding proteins as multifunctional regulators of lymphocyte development and function. Advances in Immunology 2012 May; (115): 161-185. PMID:22608259
- Turner M, Hodson D. Regulation of lymphocyte development and function by RNA binding proteins. Curr Opin Immunol. 2012 Apr;24(2):160-5. PMID:22326859
- 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. PMCID:PMC2953641
- 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. PMCID:PMC2892362