Professor Daniel Hodson

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Professor Daniel Hodson

Deciphering the genomics of B cell lymphomas

Email: djh1002@cam.ac.uk     |     Departmental Affiliation: Haematology

Research 

Research Focus: 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. The Hodson Group is developing novel cell culture models to study the effects of these genetic alterations in human lymphocytes. In particular, they are interested in studying how these genetic alterations lead to changes at the level of mRNA translation and how these posttranscriptional changes then contribute to lymphomagenesis.

The lab uses a variety of techniques including exome and RNA sequencing, ribosome profiling, iCLIP and single cell perturbational transcriptomics 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.

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Hodson Group photo

The unique and dangerous life of the B cell

Key Publications

• Gong C, Krupka JA, Gao J, Grigoropoulos NF, Giotopoulos G, Asby R, Screen M, Usheva Z, Cucco F, Barrans S, Painter D, Zaini NBM, Haupl B, Bornelöv S, Ruiz De Los Mozos I, Meng W, Zhou P, Blain AE, Forde S, Matthews J, Khim Tan MG, Burke GAA, Sze SK, Beer P, Burton C, Campbell P, Rand V, Turner SD, Ule J, Roman E, Tooze R, Oellerich T, Huntly BJ, Turner M, Du MQ, Samarajiwa SA, Hodson DJ. Sequential inverse dysregulation of the RNA helicases DDX3X and DDX3Y facilitates MYC-driven lymphomagenesis. Mol Cell. 2021 Oct 7;81(19):4059-4075. PMID: 34437837

• Morin RD, Arthur SE, Hodson DJ. Molecular profiling in diffuse large B-cell lymphoma: why so many types of subtypes? Br J Haematol. 2021 Aug 31. PMID: 34467527

• Gao J, Sidiropoulou E, Walker I, Krupka JA, Mizielinski K, Usheva Z, Samarajiwa SA, Hodson DJ. SGK1 mutations in DLBCL generate hyperstable protein neoisoforms that promote AKT independence. Blood. 2021 Sep 16;138(11):959-964. PMID: 33988691

• Caeser R, Gao, J, Di Re M, Gong J & Hodson DJ.  Genetic manipulation and immortalized culture of ex vivo primary human germinal center B cells.  Nature Protocols. 2021 Apr 9. doi: 10.1038/s41596-021-00506-4. Online ahead of print. PMID: 33837304
   
• 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 May 14;135(20):1759-1771. 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