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Nigel Jones

Dr Nigel Jones
BSc, PhD

Programme Director - BSc Pharmacology
School of Biosciences

Research

Research Interests

My research interests lay primarily in the study of the DNA damage response (DDR) and the role that DNA repair mechanisms, in particular, protect against cancer. Specific areas of activity are the human genetic disorder Fanconi anaemia (eg: DOI: 10.1016/j.molcel.2010.03.003) and the role of the dinucleotide Ap4A in the DDR (eg: DOI: 10.1016/j.dnarep.2015.06.008).

Fanconi anaemia (FA) is characterised by bone marrow failure, genetic instability and cancer predisposition, particularly acute myeloid leukaemia (AML) and head and neck squamous cell carcinoma (HNSCC). At least twenty FA genes have now been identified and the encoded proteins operate in the DDR to interstrand cross-links (ICL). This form of damage, induced by agents such as mitomycin C and cis-platin, links the two strands of DNA and stalls the progression of DNA replication. It is now believed that the FA pathway protects cells from DNA damage arising from endogenous aldehydes such as acetaldehyde and formaldehyde. Several of the FA genes are also breast cancer susceptibility genes, most notably FANCD1/BRCA2. My research on FA has focused on the role of the proteins FANCG and FANCD2, in particular how phosphorylation modulates their activity and their protein binding partners (DOI: 10.1038/sj.onc.1211034), how they function in homologous recombination repair, potential roles they may have outside of the canonical FA pathway and how they predispose to a variety of cancers including breast and cervical cancer (DOI: 10.2353/ajpath.2010.090779).

The dinucleotide diadenosine tetraphosphate (Ap4A) is synthesised in response to a variety of stresses and has previously been implicated in DNA damage responses. We have established that Ap4A plays an important role in cellular responses to DNA damaging agents, in particular ICL agents such as mitomycin C, but also aldehydes including acetaldehyde. Research on Ap4A is focused on elucidating the role Ap4A plays in mediating cellular responses to ICL and in how Ap4A may down-regulate cancer promoting genes (DOI: 10.1371/journal.pone.0154674).

Research grants

Genetic analysis of the cancer prone syndrome Fanconi anaemia: Mitomycin C - hypersensitive Chinese hamster cell mutants as a model system.

NORTH WEST CANCER RESEARCH FUND

September 2000 - September 2003

Molecular and cellular characterisation of nitrogen mustard-hypersensitive Chinese hamster cell mutants: possible models for the human syndrome Fanconi anaemia.

THE NUFFIELD FOUNDATION (UK)

June 2002 - October 2002

Homologous recombination and BRCA1/RAD51 foci formation in mammalian cell mutants defective in the Fanconi anaemia and ataxia telangiectasia DNA damage response pathways.

NORTH WEST CANCER RESEARCH FUND

September 2003 - September 2006

Regulation of DNA replication by diadenosine nucleotides after DNA damage

NORTH WEST CANCER RESEARCH FUND

October 2013 - September 2016

Interactions of the FANCD2 protein in the Fanconi-BRCA tumour suppressor pathway

YALE SCHOOL OF MEDICINE (USA)

December 2009 - November 2010

The role of the Fanconi anaemia protein FANCG in mediating the formation of a protein complex containing homologous recombination proteins BRCA2 and XRCC3 and its role in replication fork progression.

NORTH WEST CANCER RESEARCH FUND

September 2006 - September 2009

The role of diadenosine tetraphosphate (Ap4A) in the DNA damage response

NORTH WEST CANCER RESEARCH FUND

October 2010 - September 2013

Miss Batool Almarzouq - Bench fees

ROYAL EMBASSY OF SAUDI ARABIA

November 2014 - October 2017

    Research collaborations

    Dr. Gary M. Kupfer

    Yale University School of Medicine

    Investigating the role of phosphorylation in the activity of Fanconi anaemia proteins

    Prof Sandy McLennan

    Role of Ap4A in the DNA damage response

    Dr Stefan Meyer

    University of Manchester

    Translational and clinical studies of Fanconi anaemia

    Dr Andrew Marriott

    Edge Hill University

    The role of Ap4A in the DNA damage response

    Prof. Christopher G Mathew

    King's College London

    Interactions of Fanconi anaemia proteins with homologous recombination proteins

    Dr. Larry H Thompson

    Lawrence Livermore National Laboratory

    Mammalian cell mutants defective in the Fanconi Anaemia gene pathway and homologous recombination repair.

    Dr Nikki Copeland

    University of Lancaster

    Role of Ap4A in the DNA damage response/DNA replication

    Dr Roger Barraclough

    FANCD2 and triple-negative breast cancer

    Dr Janet Risk

    The Fanconi anaemia pathway in HNSCC and cervical cancer