• Room 01.062 - CEM

    United Kingdom

Accepting PhD Students

PhD projects

My team offers an ideal environment for students interested in signal transduction and molecular cell biology, as well as mouse models of disease and drug discovery targeting Grem1 and other proteins involved in human disease.

19942019

Research output per year

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Personal profile

Interests


PhD Supervisor Profile 

MBRU Partnership 

MBRU students - summer placement

 

Training/Positions Held

2009-present Lecturer/Senior Lecturer, Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, Northern Ireland, UK

Research Focus: Gremlin1 signalling in diabetic nephropathy and colorectal cancer

Sample Publications

  1. Dutton LR, O’ Neill CN, Medina R and Brazil DP (2019) No evidence that Gremlin1 activates VEGFR2 signalling in endothelial colony-forming cells. J Biol Chem (in press)
  2. Dutton LR, Hoare OP, McCorry AMB, Redmond KL, Adam NE, Bingham V, Mullan P, Lawler M, Dunne PD and Brazil DP (2019) Fibroblast-derived Gremlin1 localises to epithelial cells at the base of the intestinal crypt. OncoTarget 10:4630-4639
  3. Church RH,Ali I,Tate M, Lavin D, Krishnakumar A, Kok HM, Goldschmeding R, Martin F and Brazil DP (2017) Gremlin1 plays a key role in kidney development and renal fibrosis. Am J Physiol Renal Physiol 312:F1141-F1157
  4. Church RH, Kirshnakumar A, Urbanek A, Geschwinder S, Meneely JP, Bianchi A, Basta B, Monaghan S, Elliot C, Strömstedt M, Ferguson N, Martin F and Brazil DP (2015) Gremlin1 preferentially binds to Bone Morphogenetic Protein-2 (BMP-2) and BMP-4 over BMP-7. Biochem J 466:55-68

 

2003-2009 Group Leader/Lecturer, Department of Medicine, UCD Dublin, Ireland

Research Focus: Elucidating the signalling mechanisms involved in diabetic nephropathy 

Sample Publications

  1. Carew RM, BrowneMB, Hickey FB, and Brazil DP (2011) IRS2 and FoxO3a signalling are involved in E-cadherin expression and TGF-b1-induced repression in kidney epithelial cells. FEBS J 278:3370-80.
  2. Roxburgh SA, Curran S, Kattla JJ, Godson C, Martin F and Brazil DP (2009) Allelic depletion of Gremlin attenuates early nephropathy-like changes in a diabetic mouse model. Diabetes 58:1641-50
  3. Kattla JJ, Carew RM, Heljic M, Godson C and Brazil DP (2008) TGFb1-mediated activation of Protein kinase B/Akt is important for epithelial-mesenchymal transition in kidney cells. Am J Physiol Renal Physiol 295:F215-25

 

2000-2003 Postdoctoral Fellow in Friedrich Miescher Institute, Basel, Switzerland.

Supervisor: Dr. Brian Hemmings

Primary Project: Elucidating the role of Carboxy-Terminal Modulator Protein (CTMP) in Akt regulation

Sample Publications

  1. Brazil DP, Park J and Hemmings BA (2002) PKB Binding Proteins: Getting in on the Akt. Cell 111:293-303
  2. Maira S-M, Galetic I, Brazil DP, Kaech S, Ingley E, Thelen M, and Hemmings BA (2001). Carboxyl-terminal modulator protein (CTMP) a negative regulator of PKB and v-Akt at the plasma membrane. Science 294:374-380
  3. Hill MM, Andjelkovic M, Brazil DP, Ferarri S, Fabbro D and Hemmings BA (2001) Insulin-stimulated protein kinase B phosphorylation on Ser473 is independent of its activity and occurs through a staurosporine-insensitive kinase. J Biol Chem 276:25643-25646

 

1997-2000 Postdoctoral Fellow in Medicine, Joslin Diabetes Center, Harvard Medical School, Boston, USA.

Supervisor: Prof. Morris White

Projects: Role of IRS2 in brain development/role of PI3Kinase p55g isoform in insulin signalling

Sample Publications

  1. Schubert* M, Brazil DP* Burks DJ*, Kushner JA, Ye, J, Flint CL, Farhang-Fallah, J, Dikkes P, Warot XM, Rio C, Corfas G and White MF (2003). Insulin Receptor Substrate-2 deficiency impairs brain growth and promotes Tau phosphorylation. J Neurosci 23:7084-7092 (*co-first author)
  2. Fruman DA, Mauvais-Jarvis F, Pollard DA, Yballe CM, Brazil D, Bronson RT, Kahn CR and Cantley LC (2000). Hypoglycemia, liver necrosis and perinatal death in mice lacking all isoforms of phosphoinositide 3-kinase p85. Nature Genet 26:379-382
  3. Simoncini T, Hafezi-Moghadam A, Brazil DP, Ley K, Chin WW and Liao JK (2000) Interaction of Estrogen receptor with the regulatory subunit of phosphatidylinositol 3-kinase. Nature  407:538-541

 

1993-96 PhD Department of Pharmacology and Toxicology, University of Ulm, Germany

Supervisor: Prof. Peter Gierschik.

Project Title: Regulation of Phospholipase C-b2 by G-protein bg subunits

Sample Publications

  1. Kelly, J., Brazil, D., Clyne, C., McHale, N., Gierschik, P., and Keenan, A. (1996) Evidence for the presence of G proteins, adenylyl cyclase and phospholipase C activities in lymphatic smooth muscle cell membranes, Cell Signal  8, 425-432
  2. Dietrich, A., Brazil, D., Jensen ON., Meister, M., Schrader, M., Moomaw, JF, Mann, M., Illenberger, D., and Gierschik, P. (1996) Isoprenylation of the G-protein g subunit is both necessary and sufficient for bg dimer-mediated stimulation of phospholipase C, Biochemistry, 35, 15174-15182
  3. Dietrich A, Meister M, Brazil D, Camps M, Gierschik P (1994) Stimulation of phospholipase C-beta 2 by recombinant guanine-nucleotide-binding protein beta gamma dimers produced in a baculovirus/insect cell expression system. Requirement of gamma-subunit isoprenylation for stimulation of phospholipase C.. Eur. J. Biochem., 219, 171-178

 

1988-92 BSc Hons in Pharmacology (First Class) 1988-1992, UCD Dublin, Ireland

 

Research Statement

I lead an international team of postdocs, PhD students and MSc students focussed on the molecular cell biology of diabetic kidney disease. We are specifically interested the bone morphogenetic protein antagonist Gremlin1 (Grem1), which is implicated in fibrotic disorders of the diabetic kidney, lung and other tissues and organs. Grem1 is also implicated in many human cancers, particularly colorectal cancer, where we have demonstrated that Grem1 is highly expressed in the stromal, metastatic form of CRC (CMS4). In addition, we and others have demonstrated that Grem1 is a marker for poor patient prognosis in CRC. We employ a combined molecular cell biology/mouse knockout approach to defining the role of Grem1 in human disease. Our group has published several key papers identifying that Grem1 is a bona fide therapeutic target in DN and other diseases. Previous research projects have focussed on the role of IRS2 and Akt signalling in diabetic kidney disease.

 

Current Research Projects 

  1. The development of novel, small molecule inhibitors of Grem1 as therapeutic lead compounds for the treatment of DN, colorectal cancer and other conditions (funded by Invest NI).
  2. Using human induced pluripotent stem cells (iPS) to derive 3D kidney organoids as a replacement for mouse models (funded by NC3Rs).
  3. Defining novel aspects of Grem1 signalling in diabetic nephropathy and colorectal cancer (funded by China Queen’s College Scholarship)

 

Current Research Team

1 Postdoctoral research fellow

4 PhD students (1 Northern Ireland, 1 England, 2 China)

2 MSc students (1 India, 1 China)

1 BSc Honours Undergraduate student (NI)

 

Summer Student Research

My laboratory hosts both national and international summer students each year. Each student will spend 6-8 weeks in my laboratory carrying out an independent research project. I am the School of Medicine coordinator for the British Council IAESTE programme where international summer students from over 80 countries come to QUB for their summer studentships. I also coordinate the MBRU Dubai summer student placements at QUB-to date, 8 students from MBRU Dubai have completed placements in our research centre.

Teaching

I contribute to undergraduate medicine, dentistry and biomedical science teaching in the School of Medicine, Dentistry and Biomedical Sciences. I also contribute to postgraduate teaching in our centre and medical school. I also participate in international teaching at our China Queen’s College Campus in Shenyang, and Mohammed Bin Rashid University (MBRU) in Dubai.  My teaching includes a blend of large and small group contact, as well as flipped classroom teaching. I am also involved in the development of the new C25 Case-Based Learning curriculum which will start in our medical school in 2020.

The following are a list of my teaching activities:

Undergraduate Teaching

Medicine Year 1

MED1023: Principles of Disease and Treatment 1 (PODT1, Module Co-Coordinator)

MED1012: Personal Development Portfolio Tutor

MED1027: Physiological Basis of Clinical Practise (PCBP1)

Interprofessional Learning Workshop on Numeracy: Year 1 Medicine/Pharmacy

MED1026 Clinical and Professional Skills (CPS1)

 

Medicine Year 2

MED2011 Year 2 Medicine Integrated Case-Based Assessment

MED2014 Year 2 Medicine: Principles of Disease and Treatment 2

 

Dentistry Year 2

DEN2026 Year 2 Dentistry Pharmacology of Drugs and the Endocrine System 

 

Biomedical Science

BMS2015 Year 2 Biomedical Science Molecular Cell Biology

BMS3104 Year 3 Biomedical Science Molecular Markers of Disease

BMS3112 BSc Honours project

 

Postgraduate Teaching

MSc in Experimental Medicine

SCM8110 Diabetes and Cardiovascular Medicine: Biology and Disease

SCM8111 Diabetes and Cardiovascular Medicine: Clinical Translation

SCM8055 Generic Skills in Communicating Science

 

MSc in Bioinformatics and Computational Science

SCM7046 Introductory Cell Biology

 

International Teaching

China Queen’s College, Shenyang, China

BSc in Pharmaceutical Biotechnology

PMC3028 Personalised Medicine

 

Mohammed Bin Rashid University Medical School Dubai

Ad hoc guest teaching in Genetics and Pharmacology to Year 1/2 medical students for 1 week in March each year

 

4. Outreach Activities

I travel to meet patients groups from Diabetes UK regularly to discuss our research. I established the Know Your Enemy: Disease-Focussed Research at Queen’s public engagement event in our centre in 2016 as part of the Northern Ireland Science Festival (https://www.qub.ac.uk/research-centres/wwiem/EducationandTraining/Outreach/NIScienceFestival2019/). We host regular work-placement students and visits from schools from Northern Ireland, Spain and other locations. I have given talks at secondary schools, science fairs and other events aimed at encouraging students to pursue careers in science and medicine.

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Projects

Research Output

CAMKII as a therapeutic target for growth factor-induced retinal and choroidal neovascularisation

Ashraf, S., Bell, S., O'Leary, C., Canning, P., Micu, I., Fernandez, J. A., O'Hare, M., Barabas, P., McCauley, H., Brazil, D. P., Stitt, A. W., McGeown, J. G. & Curtis, T. M., 21 Mar 2019, In : JCI insight. 4, 6, 18 p., e122442.

Research output: Contribution to journalArticle

Open Access
File
  • 3 Citations (Scopus)
    207 Downloads (Pure)
    Open Access
    File
  • 3 Citations (Scopus)
    120 Downloads (Pure)

    No evidence of Gremlin1-mediated activation of VEGFR2 signaling in endothelial cells

    Dutton, L. R., O'Neill, C. L., Medina, R. J. & Brazil, D. P., 29 Nov 2019, In : The Journal of biological chemistry. 294, 48, p. 18041-18045 5 p.

    Research output: Contribution to journalArticle

    Open Access
    File
  • 3 Citations (Scopus)
    56 Downloads (Pure)
    Open Access
  • 3 Citations (Scopus)

    Uncoupled turnover disrupts mitochondrial quality control in diabetic retinopathy

    Hombrebueno, J. R., Cairns, L., Dutton, L. R., Lyons, T. J., Brazil, D. P., Moynagh, P., Curtis, T. M. & Xu, H., 29 Oct 2019, In : JCI insight.

    Research output: Contribution to journalArticle

    Open Access
  • Prizes

    Eleected Local Ambassodor of the Biochemical Society

    Brazil, Derek (Recipient), 2011

    Prize: Election to learned society

    FEBS Journal Prize for Young Scientists

    Brazil, Derek (Recipient), 2012

    Prize: Prize (including medals and awards)

  • Activities

    • 1 KTP & Consultancy in kind
    • 1 Editorial activity
    • 1 Membership of external research organisation

    AstraZeneca consultancy Gothenburg Sweden

    Derek Brazil (Advisor)

    2011

    Activity: Consultancy typesKTP & Consultancy in kind

    Frontiers in Pharmacotherapy and Inflammation (Journal)

    Derek Brazil (Reviews editor)

    2011 → …

    Activity: Publication peer-review and editorial work typesEditorial activity

    Faculty of 1000 (External organisation)

    Derek Brazil (Member)

    2010 → …

    Activity: Membership typesMembership of external research organisation