Faculty of Medical Sciences

Staff Profile

Professor Derek Mann

Dean of Research & Innovation (Non-Clin)

Background

Introduction

I am Dean of Research and Innovation in the Faculty of Medical Sciences and Head of the Newcastle Fibrosis Research Group (NFRG). My main research interests are the transcriptional control of inflammation, epigenetic control of fibrosis and the role of age-related chronic inflammation in ageing and cancer. Through my investigations on the functions of the transcription factor p50, a subunit of NF-kB, my group have shown that inflammation results in telomere damage and ageing.We have also discovered that p50 is an important tumour suppressor, since mice lacking p50 develop spontaneous age-related liver cancer and this is predominantly driven by neutrophils. Ongoing work funded by a CRUK programme grant is determining the mechanisms by which neutrophils promote liver cancer with the aim of designing therapeutic strategies that manipulate neutrophil behaviours. Biochemical studies in the lab are determining the mechanisms by which p50 operates as an anti-inflammatory factor and our current hypothesis is that this function is a property of a transcription repressor complex comprising p50:p50 homodimers complexed with the histone deactylase HDAC1. Our latest work suggests that p50:p50:HDAC1 complexes suppress inflammatory gene expression by promoting a repressed state of chromatin at promoters and this of particular importance at genes controlling neutrophil migration. My work on fibrosis is focussed on cross-talk between the stressed epithelium and neighbouring fibroblast/myofibroblast lineages. This work has recently identified the alarming IL-1alpha as an epithelial-derived stimulator of fibroblast expression of the monocyte chemokine CCL2, the latter a mediator of inflammation and fibrosis. Our fibrosis research works across multiple tissues and disease types including liver, lung, kidney, heart, skin and joints. The aim of the work is to identify pathways such as the IL-1/CCL2 pathway that are able to be targeted with drugs currently in clinical development. Additional studies are determining epigenetic changes that occur in hepatocytes and liver myofibroblasts in non-alcoholic fatty liver disease (NAFLD) with the aim of identifying biomarkers of disease progression to cirrhosis and cancer. Fibrosis research in the NFRG is funded by an MRC MICA Programme Grant in collaboration with GSK. In June 2017 I was elected a Fellow of the Academy of Medical Sciences and in 2019 was selected as Regional Champion for the Academy.

Lab website https://research.ncl.ac.uk/fibrosislab/

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Research

Research Interests

Tissue fibrosis, Inflammation, Ageing, Cancer.

Gene regulation (epigenetic and transcriptional)

Cell biology of myofibroblasts and neutrophils.

Current Work

Discovery of therapies for the prevention and treatment of chronic liver disease and cancer.

Discovery of biomarkers and therapeutic targets for tissue fibrosis.

Understanding the basic regulatory mechanisms that control cell phenotype, function and fate with the emphasis on events at the level of gene transcription.

Research Roles

Group Leader

Postgraduate Supervision

Currently supervise several PhD students

Esteem Indicators

Fellow of the Academy of Medical Sciences (2017)

Funding

GSK Programme.

8-year pre-clinical research programme aimed at discovering biomarkers of fibrosis and advancing anti-fibrotics into clinical studies. £1.4M. 2011 – 2019. Mann is PI.  

  

 NIAAA (NIH) UO1 Collaborator Programme Grant.

Epigenetic regulation of alcoholic liver fibrosis. $2M. 2016 - 2021. Mann is joint PI.

 

MRC/Newcastle Lifelong Health and Wellbeing Centre for Ageing and Vitality. £3,500,000. 2015-2020. Mann is Co-Director (Sir Doug Turnbull is Director).

 

EU Collaborative Grant.

Elucidating Pathways of Steatohepatitis. Euros 6M. 2015-2019. Mann named

investigator.

 

Abbvie. Collaborative research investigating mechanisms of fibrosis in non-alcoholic fatty liver disease. 2016-2018. £594,195. Mann is PI.

 

Abbvie. Collaborative research aimed at identifying biomarkers that predict fibrosis progression in non-alcoholic fatty liver disease. 2016-2018. £597,701. Mann is Co-I.

 

Cancer Research UK (CRUK) Programme Grant.

Towards targeting neutrophils in hepatocellular carcinoma. 2017-2021. £1,740,000. Mann is joint PI.


MRC MICA Programme Grant (in collaboration with GSK).

Molecular drivers of fibrosis at the hepatic epithelial-mesenchymal barrier. circa-£2M.

2018-2022. Mann is PI.

Industrial Relevance

Funded collaborations with GSK and Abbvie.

Patents

US200519130
WO2004019921
W02006072783
EP1531825

Publications