Matthew Brook
Principal Investigator (UoE/CVS) and Lecturer (UoE/ZJE)

Address
- Street
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Centre for Cardiovascular Science
Queen's Medical Research Institute
University of Edinburgh
Edinburgh Bioquarter
47 Little France Crescent
Edinburgh - City
- Post code
- EH16 4TJ
Qualifications
BSc Biochemistry: University of Essex
MPhil Biochemistry: University of Manchester (Regulation of proliferation and differentiation of the rat intestinal epithelium)
PhD Molecular Biochemistry: Imperial College London (Regulation of TNF-alpha gene expression by p38 mitogen-activated protein kinase)
Responsibilities & affiliations
Biochemical Society - Member of Research Area I (Genes) panel & Local Ambassador for University of Edinburgh
Centre for Cardiovascular Sciences - Research Integrity Academic Lead
Undergraduate teaching
Assistant Professor at Zhejiang University-University of Edinburgh (ZJE) Institute, lecturing on the Biomedical Sciences Joint Honours degree program.
Joint Coordinator of Years 3&4 for the Integrated Biomedical Sciences (BMS) and Biomedical Bioinformatics (BMI) degree programmes.
Course Organiser for "Integrated Biomedical Science 4 (IBMS4)" and "Future Perspectives" 4th year courses.
Open to PhD supervision enquiries?
Yes
Current PhD students supervised
Natasha Arzoo (PhD Student - Co-Supervised by Dr. Robert Young (Usher Institute, UoE) [Pakistan HEC Scholarship]
Honglin Yu (PhD Student ZJE Institute, China - Co-Supervisor with Dr. Di Chen (ZJE Institute)
Qizhe Shao (PhD Student ZJE Institute, China - Co-Supervisor with Dr. Di Chen (ZJE Institute)
Junping Shi (PhD Student ZJE Institute, China - Co-Supervisor with Dr. Xianghua Li (ZJE Institute) and Dr. Robert Young (Usher Institute, UoE)
Hongling Liu (PhD Student - Co-Supervisor with Prof. Nik Morton (PI) (UoE/Nottingham-Trent University), Prof. Kei Sakamoto (CBMR, Uni. Copenhagen)
Triin Ounapuu (PhD Student - Co-Supervisor with Prof. Nicola Gray (PI))
Past PhD students supervised
Shiyang He (MSc)
Ana Ingels (MSc)
Saidiburkhaniddin Adikhanov (MSc)
Lara Scheer (MSc)
Yan Xu (MSc)
Yanjing Zhao (MSc)
Co-Supervised with Prof. Nicola Gray:
Mathias Lorbeer (PhD)
Hristina Gyurova (PhD)
Tajekesa Blee (PhD)
Lenka Hrabalkova (PhD)
Jessica Scanlon (PhD)
Sarah Howard (MSc)
Maria Casacao (MSc)
Huanting Chi (MSc)
Emily Walshe (MSc)
Melina Michael (BSc)
Rachael Smith (BSc)
Research summary
I am fascinated by the molecular 'circuitry' that underpins a cell's ability to produce all the proteins it requires for its viability and correct function. Without this 'circuitry' there would be nothing to ensure that proteins are made at the right time, in the correct location and in the correct amounts, therefore it is essential for life. However, the combinations of intracellular signalling and responsive gene expression that comprise the molecular 'circuits' do not always work perfectly, e.g. due to gene mutations and/or environmental influences (such as diet) and this can lead to morbidity/disease (e.g. cancer, metabolic and cardiovascular disease, neurodegenerative disease, reproductive disorders etc.....).
It is therefore crucial that we first determine the normal cellular mechanisms that control protein synthesis. By identifying the mechanistically-required protein and RNA factors and, critically, by delineating the way in which signals from outside and inside the cell are relayed to these factors, we build a platform from which to begin understanding how protein synthesis becomes dysregulated in disease/morbidity.
Unfortunately, vast proportions of the molecular circuitry of normal metabolic and cardiovascular health remain to be uncovered and we are therefore unable to fully understand the mechanisms by which metabolic and cardiovascular diseases arise and/or progress. We aim to change this.
Current research interests
In the lab, we take complementary approaches to deciphering post-transcriptional regulation: 1) We take a targeted approach and simultaneously work to understand i) how specific RNA-binding proteins (RBPs) function to coordinate gene expression, ii) how specific RNA-binding protein functions are regulated by post-translational modifications (such as phosphorylation, acetylation and methylation) in response to specific cellular signals and iii) what signalling pathways and effector enzymes carry out these specific post-translational modifications. 2) We take an agnostic approach and aim to elucidate the post-transcriptional molecular circuitry of disease/morbidity by identifying expression and/or post-translational modification changes in the total cellular RBP-ome and changes in the RNA-binding status of all expressed RBPs (general and substrate-specific). These are multidisciplinary investigations that require both routine and cutting-edge methodologies and expertise (e.g. site-specific post-translational modification of recombinant proteins using codon extension/unnatural amino acids, surface plasmon resonance, X-ray crystallography, quantitative mass spectrometry, RBP interactome capture) and which range from in vitro methods using purified components through to in vivo physiology……and all in between. 3) Working with key collaborators at University of Edinburgh and The Centre for Basic Metabolic Research (CBMR), University of Copenhagen, Denmark, we employ population genetics approaches combined with genome-wide gene expression dataset analyses to identify human genetic variants that directly or indirectly affect post-transcriptional regulation of gene regulatory networks underpinning cardiometabolic health and disease.Past research interests
My previous projects have primarily centred around specific RNA-binding proteins such a Tristetraprolin (TTP) or members of the poly(A)-binding protein (PABP) family. I remain actively involved in understanding the molecular and physiological functions of PABPs and how they are regulated.Project activity
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Identification and characterization of heart RNA-binding protein-mediated gene expression and its dysregulation in obesity-induced Diabetic Cardiomyopathy (DCM). (Collab. with Dr. Robert Young (Usher Institute, UoE)
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Quantification and mechanistic characterisation of the extensive post-transcriptional regulation underpinning adipogenesis in human health and obesity. [Collab. with Dr. Tuomas Kilpelainen (CBMR, Uni. Copenhagen), Prof. Roland Stimson (CVS, UoE) and Dr. Alex Von Kriegsheim (IGC, UoE)
Current project grants
"Identifying mRNA 3’UTR and 5’UTR region cardiometabolic GWAS variants and quantifying their effect on the post-transcriptional regulation of gene expression underpinning human adipogenesis."
Awarded amount: £21,724
British Heart Foundation REA3 Pump Prime grant
"In vivo, genome-wide identification of the post-transcriptional regulation in heart that underpins the life-course of obesity-induced diabetic cardiomyopathy."
Awarded amount: £5,000
British Heart Foundation REA3 Pump Prime grant
Past project grants
"In vivo, genome-wide identification of the post-transcriptional regulation in heart and skeletal muscle that underpins the life-course of obesity-induced diabetes and cardiovascular disease"
Awarded amount: £28,632
British Heart Foundation REA3 Pump Prime grant
“Does PABP4 control diet-induced obesity, by acting as a master regulator of metabolism-related gene expression?”
Awarded amount: £545,841
BBSRC Project Reference: BB/R004668/1 [Dec 2017 - Dec 2020]
Lead author and Co-I (PI, Prof. Nicola Gray; Co-I, Prof. Nik Morton)
"Can histone code-like 'switches' govern the multi-functionality of RNA-binding proteins?"
Awarded amount: £723,957
BBSRC Project Reference: BB/P022065/1 [Sep 2017 - Sep 2020]
Lead author/Co-Investigator (PI, Prof. Nicola Gray; Co-I, Dr. Atlanta Cook)
“Poly(A)-binding proteins highlight the importance of regulated mRNA translation and stability in determining a functional maternofetal interface”
Awarded amount: £1.4M
MRC Program Grant [2012-2017]
Joint Co-Author (PI, Prof. Nicola Gray)
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Neutrophil-derived alpha defensins control inflammation by inhibiting macrophage mRNA translation
(6 pages)
In:
Proceedings of the National Academy of Sciences (PNAS), vol. 113, pp. 4350-4355
DOI: https://doi.org/10.1073/pnas.1601831113
Research output: Contribution to Journal › Article (Published) -
Modulation of the cytoplasmic functions of mammalian post‐transcriptional regulatory proteins by methylation and acetylation: a key layer of regulation waiting to be uncovered?
In:
Biochemical Society Transactions, vol. 43, pp. 1285-95
DOI: https://doi.org/10.1042/BST20150172
Research output: Contribution to Journal › Article (Published) -
The role of mammalian poly(A)-binding proteins in co-ordinating mRNA turnover
(9 pages)
In:
Biochemical Society Transactions, vol. 40, pp. 856-64
DOI: https://doi.org/10.1042/BST20120100
Research output: Contribution to Journal › Article (Published) -
A Molecular Doorstop Ensures a Trickle through Translational Repression
(3 pages)
In:
Cell, vol. 149, pp. 13-15
DOI: https://doi.org/10.1016/j.cell.2012.03.010
Research output: Contribution to Journal › Editorial (Published) -
The multifunctional poly(A)-binding protein (PABP) 1 is subject to extensive dynamic post-translational modification, which molecular modelling suggests plays an important role in co-ordinating its activities
(10 pages)
In:
Biochemical Journal, vol. 441, pp. 803-812
DOI: https://doi.org/10.1042/BJ20111474
Research output: Contribution to Journal › Article (Published) -
DAZAP1, an RNA-binding protein required for development and spermatogenesis, can regulate mRNA translation
(14 pages)
In:
RNA, vol. 17, pp. 1282-1295
DOI: https://doi.org/10.1261/rna.2717711
Research output: Contribution to Journal › Article (Published) -
Poly(A)-binding proteins are functionally distinct and have essential roles during vertebrate development
(6 pages)
In:
Proceedings of the National Academy of Sciences (PNAS), vol. 108, pp. 7844-7849
DOI: https://doi.org/10.1073/pnas.1017664108
Research output: Contribution to Journal › Article (Published) -
Cytoplasmic mRNA: move it, use it or lose it!
(5 pages)
In:
Biochemical Society Transactions, vol. 38, pp. 1495-9
DOI: https://doi.org/10.1042/BST0381495
Research output: Contribution to Journal › Article (Published) -
Poly(A)-binding protein 1 partially relocalizes to the nucleus during herpes simplex virus type 1 infection in an ICP27-independent manner and does not inhibit virus replication
(10 pages)
In:
Journal of Virology, vol. 84, pp. 8539-8548
DOI: https://doi.org/10.1128/JVI.00668-10
Research output: Contribution to Journal › Article (Published) -
Themis2/ICB1 is a signaling scaffold that selectively regulates macrophage Toll-like receptor signaling and cytokine production
In:
PLoS ONE, vol. 5, pp. e11465
DOI: https://doi.org/10.1371/journal.pone.0011465
Research output: Contribution to Journal › Article (Published) -
The DAZL and PABP families: RNA-binding proteins with interrelated roles in translational control in oocytes
(23 pages)
In:
Reproduction, vol. 137, pp. 595-617
DOI: https://doi.org/10.1530/REP-08-0524
Research output: Contribution to Journal › Literature review (Published) -
Posttranslational regulation of tristetraprolin subcellular localization and protein stability by p38 mitogen-activated protein kinase and extracellular signal-regulated kinase pathways
(11 pages)
In:
Molecular and Cellular Biology, vol. 26, pp. 2408-18
DOI: https://doi.org/10.1128/MCB.26.6.2408-2418.2006
Research output: Contribution to Journal › Article (Published) -
Mitogen-activated protein kinase-activated protein kinase 2 regulates tumor necrosis factor mRNA stability and translation mainly by altering tristetraprolin expression, stability, and binding to adenine/uridine-rich element
(9 pages)
In:
Molecular and Cellular Biology, vol. 26, pp. 2399-407
DOI: https://doi.org/10.1128/MCB.26.6.2399-2407.2006
Research output: Contribution to Journal › Article (Published) -
The stability of tristetraprolin mRNA is regulated by mitogen-activated protein kinase p38 and by tristetraprolin itself
(8 pages)
In:
Journal of Biological Chemistry, vol. 279, pp. 32393-400
DOI: https://doi.org/10.1074/jbc.M402059200
Research output: Contribution to Journal › Article (Published) -
Mitogen-activated protein kinase p38 controls the expression and posttranslational modification of tristetraprolin, a regulator of tumor necrosis factor alpha mRNA stability
(9 pages)
In:
Molecular and Cellular Biology, vol. 21, pp. 6461-9
Research output: Contribution to Journal › Article (Published) -
Dexamethasone destabilizes cyclooxygenase 2 mRNA by inhibiting mitogen-activated protein kinase p38
(10 pages)
In:
Molecular and Cellular Biology, vol. 21, pp. 771-80
DOI: https://doi.org/10.1128/MCB.21.3.771-780.2001
Research output: Contribution to Journal › Article (Published) -
Regulation of tumour necrosis factor alpha mRNA stability by the mitogen-activated protein kinase p38 signalling cascade
(5 pages)
In:
FEBS Letters, vol. 483, pp. 57-61
Research output: Contribution to Journal › Article (Published) -
p38 mitogen-activated protein kinase regulates cyclooxygenase-2 mRNA stability and transcription in lipopolysaccharide-treated human monocytes
(6 pages)
In:
Journal of Biological Chemistry, vol. 274, pp. 264-9
Research output: Contribution to Journal › Article (Published) -
A p38 MAP kinase inhibitor regulates stability of interleukin-1-induced cyclooxygenase-2 mRNA
(6 pages)
In:
FEBS Letters, vol. 439, pp. 75-80
Research output: Contribution to Journal › Article (Published)
Organiser
Translation UK 2010: Biochemical Society Focussed meeting