Dr Daniel Hodson

Mutation timing in lymphomagenesis

Email: djh1002@cam.ac.uk

Laboratory: Cambridge Stem Cell Institute, Jeffrey Cheah Biomedical Centre

Departmental Affiliation: Haematology

Biography

Daniel 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.

Funding

MRC, Bloodwise, Cancer Research UK, Gilead

The unique and dangerous life of the B cell

Research

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 6^th 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. 　

Group Members

Rebecca Caeser, Miriam Di Re, Jane Gao, Jade Gong, Joanna Krupka, Hendrik Runge, Eirini Siridopoulou, Zelvera Usheva                

Key Publications

• Gong C, Krupka JA, Gao J, Grigoropoulos NF, Screen M, Usheva Z, Cucco F, Barrans S, Painter D, Mohammed M, Haupl B, Bornelöv S, Ruiz De Los Mozos I, Meng W, Zhou P, Blain AE, Forde S, Matthews M, Tan Guet Khim M, Burke GAA, Siu Kwan N, Beer P, Burton C,  Campbell P, Rand R, Turner S, Ule J, Roman R, Tooze R, Oellerich T, Turner M, Du MQ, Samarajiwa S & Hodson DJ. Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis. Cell Press Sneak Peek doi.org/10.2139/ssrn.3520953.

• Lacey S, Barrans S, Beer P, Painter D, Smith A, Roman E, Cooke S, Ruiz C, Glover P, Van Hoppe S, Webster N, Campbell P, Tooze R, Patmore R, Burton C, Crouch S & Hodson DJ. Targeted sequencing in DLBCL, molecular subtypes and outcomes: a Haematological Malignancy Research Network report. Blood. 2020 Mar 18. PMID: 32187361

• Caeser R, Di Re M, Krupka JA, Gao J, Lara-Chica M, Dias J, Cooke S, Fenner R, Usheva Z, Runge H, Beer PA, Eldaly H, Pak HK, Park CS, Vassiliou G, Huntly BJP, Mupo A, Bashford-Rogers RJM & Hodson DJ. Genetic modification of primary human B cells generates translationally-relevant models of high-grade lymphoma. Nature Communications. 2019 Oct 4;10(1):4543. PMID: 31586074

• Schmitz R, Wright GW, Huang DW, Johnson CA, Phelan JD, Wang JQ, Roulland S, Kasbekar M, Young RM, Shaffer AL, Hodson DJ, Xiao W, Yu X, Yang Y, Zhao H, Xu W, Liu X, Zhou B, Du W, Chan WC, Jaffe ES, Gascoyne RD, Connors JM, Campo E, Lopez-Guillermo A, Rosenwald A, Ott G, Delabie J, Rimsza LM, Tay Kuang Wei K, Zelenetz AD, Leonard JP, Bartlett NL, Tran B, Shetty J, Zhao Y, Soppet DR, Pittaluga S, Wilson WH and Staudt LM. Genetics and Pathogenesis of Diffuse Large B-Cell Lymphoma. New England Journal of Medicine. 2018 Apr 12;378(15):1396-1407. PMID: 29641966

• 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. Proceedings of the National Academy of Sciences U S A. 2016 Apr 5;113(14):E2039-46. PMID: 26993806