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The University of Southampton
01722 429080

Professor Nick Cross MA, PhD, FRCPath

Professor of Human Genetics, Director, Wessex Regional Genetics Laboratory

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Professor Nick Cross is Professor of Human Genetics within Medicine at the University of Southampton.

Nick Cross read Natural Sciences at Cambridge University and stayed on to do a PhD in the Department of Genetics. He moved to the Hammersmith Hospital in 1987, where he developed an interest in leukaemia. Working initially on the development of quantitative molecular assays to determine the response of patients to therapy, he developed a research programme aimed at understanding the molecular genetics of myeloid neoplasms. This work has resulted more than 350 peer reviewed publications and is continuing in Salisbury, where he relocated in 2001 to take up Directorship of the Wessex
Regional Genetics Laboratory and a Chair of Human Genetics at the University of Southampton. In 2002 he led a successful bid to establish one of two
National Genetics Reference Laboratories (NGRL), with a focus on the development, validation and standardisation of genetic tests.


Appointments held

Research interests

Nick Cross is interested in the molecular pathogenesis of haematological malignancies, in particular chronic myeloid leukaemia (CML), myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS).

Analysis of chromosome abnormalities

Initially our work focused on the analysis of chromosome translocations which, despite being uncommon, proved to be an important route towards understanding the molecular pathogenesis of myeloid malignancies, and particular patients with unexplained eosinophilia. We have characterized more than 25 different translocations and found that the majority result in fusion genes encoding chimaeric proteins with an N-terminal region derived from a partner gene fused in frame to the C-terminal region of a tyrosine kinase such as ABL, PDGFRα, PDGFRβ, JAK2, KIT or FGFR1. Tyrosine kinases are excellent drug targets and have used a number of preclinical models to evaluate the efficacy of novel small molecule inhibitors against activated tyrosine kinases in myeloid disorders.

Genomewide genetic profiling

Our principal focus has been the use of genomewide profiling techniques to identify novel, somatically acquired genetic abnormalities. Recently our focus has been on whole exome, whole genome and RNA sequencing to identify novel mutations, particularly those found in association with acquired uniparental disomy. Notable achievements have been the finding of recurrent mutations in genes encoding the signalling regulator CBL (Grand et al. Blood 2009) the polycomb group protein EZH2 (Ernst et al. Nature Genetics 2010) and PRR14L, a gene of unknown function (Chase et al., Leukemia 2019). Other candidate abnormalities and genomic regions are currently under investigation, as is the functional analysis of novel changes.

Genetic predisposition to myeloid disorders

Many MPN are characterised by the presence of the acquired JAK2 V617F mutation. We made the remarkable finding that this mutation does not arise randomly, but rather it is seen preferentially on a common JAK2 haplotype that we have called 46/1 (Jones et al. Nature Genetics 2009). The molecular basis for this predisposition is under investigation but must presumably be a consequence of increased mutation rates (hypermutability hypothesis) or a functional difference in JAK2 that confers a selective advantage when this gene is mutated (fertile ground hypothesis). In collaboration with Dr Will Tapper we are undertaking genomewide association studies to define other genetic loci that predispose to MPN (e.g. Tapper et al., Nature Communications 2015) as well as investigating the relationship between age-related clonal haematopoiesis and the development of myeloid neoplasms.

Development and standardisation of genetic tests

We have had a long standing interest in the development of genetic tests, and one of our main areas of current activity is the standardisation of molecular monitoring of CML patients by RT-qPCR for BCR-ABL mRNA. We have developed primary, World Health Organisation approved reference reagents for BCR-ABL testing (White et al. Blood 2010) and are working with colleagues in Europe and internationally to help improve and standardise laboratories testing for minimal residual disease in CML (Cross et al., Leukemia 2012; Cross et al., Leukemia 2015).


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Professor Nick Cross
Wessex Regional Genetics Laboratory, Salisbury District Hospital, Salisbury SP2 8BJ UK

Room Number: WRGL Salisbury/4.14.04

Telephone:01722 429080

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