Biography

  • Director of Research
  • Head of the Pharmacology Section
  • Chair of the Athena SWAN committee
  • Course co-ordinator for BSc Pharmacology and Drug Discovery
  • Course co-ordinator for Science without Borders 

Maria obtained a BSc in human nutrition at Trinity College Dublin and a diploma in dietetics at Dublin Institute of Technology. She then undertook a PhD and post-doc position in Dermot Kelleher's lab at Trinity College investigating mechanisms of action of tumour necrosis factor alpha. She then moved to The Scripps Research Institute in California as an American Heart Association research fellow in Nigel Mackman's lab, studying gene regulation in inflammation.

From 1999-2006, Maria was a senior research scientist and deputy head of the Micronutrient Research Section at the Medical Research Council’s Human Nutrition Research Centre in Cambridge, working on the regulation of gene expression in inflammation and vascular disease and the role of cellular and dietary antioxidants in disease.

Research Interests

Current research interests are focused on the following areas:

  • Age-related disease and cellular antioxidants
  • Resolution of Inflammation – new targets and mechanisms of action
  • Dietary, plant and marine bioactives – mechanisms of action in inflammation and chronic disease
  • Novel therapeutics for cancer 

 

PhD positions

Click here for current PhD opportunities in PHA. But feel free to email me to discuss projects outside these areas and alternative sources of funding.

Selected publications

Anti-inflammatory effect of a cell-penetrating peptide targeting the Nrf2/Keap1 interaction.
R. Steel, J. Cowan, E. Payerne, M.A. O’Connell, M. Searcey,
ACS Med Chem Letts, 2012, 3, 407-410.
DOI: 10.1021/ml300041g

Vitamin D: potential in the prevention and treatment of lung cancer.
R. Norton, M.A. O’Connell,
Anticancer Res, 2012, 32, 211-221.

Lipopolysaccharide induced expression of NQO1 and HO-1 protects against excessive inflammatory responses
S.A. Rushworth, D.J. MacEwan and M.A. O’Connell,
J Immunol, 2008, 181, 6730–673.

Epigallocatechin activates heme oxygenase-1 expression via protein kinase Cd and Nrf2
R.M. Ogborne, S.A. Rushworth and M.A. O’Connell,
Biochem Biophys Res Commun, 2008, 373, 584-588.
DOI: 10.1016/j.bbrc.2008.06.068

Tumor necrosis factor a SNP haplotypes are associated with iron deficiency anemia in West African children
S.H. Atkinson, K. Rockett, P.A. Bejon, G. Morgan, G. Sirugo, M.A. O’Connell, N. Hanchard, D.P. Kwiatkowski and A.M. Prentice
Blood, 2008, 112, 4276-83.
DOI: 10.1182/blood-2008-06-162008

All Publications

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Williams, M., Green, A. I., Fernandez-Cestau, J., Hughes, D. L., O'Connell, M. A., Searcey, M., Bertrand, B., Bochmann, M.

(2017)

(C^Npz^C)AuIII complexes of acyclic carbene ligands: synthesis and anticancer properties,

in Dalton Transactions

46

(39)

pp. 13397–13408

Full Text UEA Repository

(Article)

(Published)


Warner, E. F., Smith, M. J., Zhang, Q., Raheem, K. S., O'Hagan, D., O'Connell, M. A., Kay, C. D.

(2017)

Signatures of anthocyanin metabolites identified in humans inhibit biomarkers of vascular inflammation in human endothelial cells,

in Molecular Nutrition & Food Research

61

(9)

article no. 1700053

Full Text UEA Repository

(Article)

(Published)


Beekman, A. M., O'Connell, M. A., Howell, L. A.

(2017)

Peptide-Directed Binding for the Discovery of Modulators of α-Helix-Mediated Protein-Protein Interactions: Proof-of-Concept Studies with the Apoptosis Regulator Mcl-1,

in Angewandte Chemie International Edition

56

(35)

pp. 10446–10450

Full Text UEA Repository

(Article)

(Published)


Reed, J., Stephenson, M. J., Miettinen, K., Brouwer, B., Leveau, A., Brett, P., Goss, R. J. M., Goossens, A., O'Connell, M. A., Osbourn, A.

(2017)

A translational synthetic biology platform for rapid access to gram-scale quantities of novel drug-like molecules,

in Metabolic Engineering

42

pp. 185–193

Full Text UEA Repository

(Article)

(Published)


Bertrand, B., Fernandez-Cestau, J., Angulo, J., Cominetti, M. M., Waller, Z. A., Searcey, M., O'Connell, M. A., Bochmann, M.

(2017)

Cytotoxicity of Pyrazine-Based Cyclometalated (C^Npz^C)Au(III) Carbene Complexes: Impact of the Nature of the Ancillary Ligand on the Biological Properties,

in Inorganic Chemistry

56

(10)

pp. 5728–5740

Full Text UEA Repository

(Article)

(Published)


Bertrand, B., Romanov, A. S., Brooks, M., Schmidt, C., Ott, I., O'Connell, M. A., Bochmann, M.

(2017)

Synthesis, structure and cytotoxicity of cyclic (alkyl)(amino) carbene and acyclic carbene complexes of group 11 metals,

in Dalton Transactions

46

pp. 15875-15887

Full Text UEA Repository

(Article)

(Published)


Beekman, A. M., O'Connell, M. A., Howell, L. A.

(2016)

Identification of small-molecule inhibitors of the antiapoptotic protein myeloid cell leukaemia-1 (Mcl-1),

in ChemMedChem

11

(8)

pp. 840–844

Full Text

(Letter)

(Published)


Warner, E. F., Zhang, Q., Raheem, K. S., O'Hagan, D., O'Connell, M. A., Kay, C. D.

(2016)

Common phenolic metabolites of flavonoids, but not their unmetabolized precursors, reduce the secretion of vascular cellular adhesion molecules by human endothelial cells,

in Journal of Nutrition

146

(3)

pp. 465-473

Full Text UEA Repository

(Article)

(Published)


Codoni, D., Cowan, J., Bradley, J., O'Connell, M., McAuley, W., Qi, S.

(2015)

Disc-shaped polyoxyethylene glycol glycerides gel nanoparticles as novel protein delivery vehicles,

in International Journal of Pharmaceutics

496

(2)

pp. 1015-1025

Full Text UEA Repository

(Article)

(Published)


Cominetti, M., Goffin, S., Raffel, E., Turner, K., Ramoutar, J., O'Connell, M., Howell, L., Searcey, M.

(2015)

Identification of a new p53/MDM2 inhibitor motif inspired by studies of chlorofusin,

in Bioorganic & Medicinal Chemistry Letters

25

(21)

pp. 4878-4880

Full Text UEA Repository

(Article)

(Published)


Stephenson, M., Howell, L., O'Connell, M., Fox, K. R., Adcock, C., Kingston, J., Sheldrake, H., Pors, K., Collingwood, S., Searcey, M.

(2015)

Solid-phase synthesis of duocarmycin analogues and the effect of C-terminal substitution on biological activity,

in The Journal of Organic Chemistry

80

(19)

pp. 9454–9467

Full Text UEA Repository

(Article)

(Published)


Di Gesso, J., Kerr, J., Zhang, Q., Raheem, S., Krishna Yalamanchili, S., O'Hagan, D., Kay, C., O'Connell, M.

(2015)

Flavonoid metabolites reduce tumor necrosis factor-α secretion to a greater extent than their precursor compounds in human THP-1 monocytes,

in Molecular Nutrition & Food Research

59

(6)

pp. 1143–1154

Full Text UEA Repository

(Article)

(Published)


Waller, Z. A. E., Howell, L. A., Macdonald, C. J., O'Connell, M. A., Searcey, M.

(2014)

Identification and characterisation of a G-quadruplex forming sequence in the promoter region of nuclear factor (erythroid-derived 2)-like 2 (Nrf2),

in Biochemical and Biophysical Research Communications

447

(1)

pp. 128-32

Full Text UEA Repository

(Article)

(Published)


Tortorici, M., Borrello, M. T., Tardugno, M., Chiarelli, L. R., Pilotto, S., Ciossani, G., Vellore, N. A., Bailey, S. G., Cowan, J., O'Connell, M., Crabb, S. J., Packham, G., Mai, A., Baron, R., Ganesan, A., Mattevi, A.

(2013)

Protein recognition by short peptide reversible inhibitors of the chromatin-modifying LSD1/CoREST lysine demethylase,

in ACS Chemical Biology

8

(8)

pp. 1677-1682

Full Text UEA Repository

(Article)

(Published)


Howell, L. A., Bowater, R. A., O'Connell, M. A., Reszka, A. P., Neidle, S., Searcey, M.

(2012)

Synthesis of Small Molecules Targeting Multiple DNA Structures using Click Chemistry,

in ChemMedChem

7

(5)

pp. 792-804

Full Text UEA Repository

(Article)

(Published)


Norton, R., O'Connell, M.

(2012)

Vitamin D: Potential in the prevention and treatment of lung cancer,

in Anticancer Research

32

pp. 211-222

UEA Repository

(Article)

(Published)


Steel, R., Cowan, J., Payerne, E., O'Connell, M., Searcey, M.

(2012)

Anti-inflammatory effect of a cell penetrating peptide targeting the Nrf2/Keap1 interaction.,

in ACS Medicinal Chemistry Letters

3

pp. 407-410

Full Text UEA Repository

(Article)

(Published)


Howell, L., Waller, Z., Bowater, R., O'Connell, M., Searcey, M.

(2011)

A small molecule that induces assembly of a four way DNA junction at low temperature,

in Chemical Communications

47

(29)

pp. 8262-8264

Full Text UEA Repository

(Article)

(Published)


Norton, R., Sexton, D. W., Clark, I. M., Wilson, A. M., Hughes, D. A., O'Connell, M. A.

(2011)

Immunomodulatory effects of 1,25(OH)(2)D-3 in normal and transformed human lung epithelium,

in Anticancer Research

31

(4)

pp. 25

UEA Repository

(Article)

(Published)


Robbins, D., Newton, A., Gignoux, C., Legeay, J., Sinclair, A., Rejzek, M., Laxon, C., Lewis, W., Yalamanchili, S., O'Connell, M., Stockman, R.

(2011)

Synthesis of natural-product-like scaffolds in unprecedented efficiency via a 12-fold branching pathway,

in Chemical Science

11

(2)

pp. 2232-2235

Full Text UEA Repository

(Article)

(Published)


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Key Research Interests

  • New therapeutic targets in the resolution of inflammation
    • Nrf2
    • TREM-2

       
  • Natural products and analogues as anti-inflammatory and anti-proliferative agents
    • Vitamin D
    • Garlic organosulfur compounds
    • Triterpenoids
    • Flavonoids and their metabolites
    • Novel leads from natural product-based libraries



Nrf2 in disease prevention and therapy

Role in inflammation
During inflammation, intracellular signalling pathways are activated to protect immune cells. The antioxidant response element (ARE) is present in the regulatory regions of several classes of antioxidant, detoxification and cytoprotective genes. The NF-E2 family of transcription factors bind to the ARE and mediate gene transcription. We are investigating the role of members of the NFE2 family, including Nrf2 and Bach1, in activation of the ARE signalling pathway in response to pro-inflammatory stimuli and examining crosstalk with other signalling pathways.

Targeting Nrf2
Over the past few years, we have identified several natural products that activate the Nrf2-anti-oxidant response pathway and have been studying their mechanisms of action and potential as future pharmaceuticals or nutraceuticals, including various flavonoids, alpha lipoic acid and novel chalcones and triterpenoids.

In addition, in collaboration with Mark Searcey (UEA), we are designing new molecules that directly interact with Nrf2 to activate this important pathway.

TREM-2 in inflammation

TREM-2 is a receptor on myeloid cells. Unlike other members of the TREM family, TREM-2 appears to exert anti-inflammatory effects in these cells. We are studying the regulation of TREM-2 in these cells and its expression and role in various cell types.

Natural products and analogues as anti-inflammatory and anti-proliferative agents

Immunomodulatory effects of vitamin D
The role of vitamin D in calcium homeostasis is well established. However, 1,25-OHD also exhibits potent antiproliferative and differentiative effects and exerts immunomodulatory effects in innate and adaptive immunity. In collaboration with David Hughes, Andrew Wilson, Darren Sexton and Ian Clark (UEA), we have been investigating the molecular mechanisms by which the active form of vitamin D modulate inflammatory mediators in human airway epithelial cells.

Cardiovascular and anti-inflammatory benefits of flavonoids and their metabolites
In collaboration with Colin Kay (UEA), we are investigating the collective beneficial activities of a series of flavonoids and their metabolites in monocytes, endothelial and smooth muscle cells and investigating their intracellular mechanisms of action.

Novel leads from natural product-based libraries
Natural products serve as a basis for developing novel therapeutic compounds. In a series of collaborations, we are identifying anti-inflammatory and anti-proliferative mechanisms of action of specific natural products and their analogues. We are studying the selective mechanisms of action of compounds from natural product-based libraries, with Mark Searcey’s group (UEA). In collaboration with Rob Stockman (Nottingham) and Sue Matthews  (UEA), we are studying analogues of marine and plant natural products and their effects on pro-inflammatory signalling pathways. With Anne Osbourn (John Innes Centre), we are studying biological effects of triterpenoids in animal cells.

 

Research Group Membership

Current

James Reed (with Anne Osbourn)

Michael Smith (with Colin Kay)

 

 

 

Past

Tyler Woodrisge

Eunice Lee

Richard Steel (with Mark Searcey)

Michael Stephenson (with Mark Searcey)

Emily Warner (with Colin Kay)

Alexandra Horton (with Phil Page)

Marco Cominetti (with Sue Matthews)

Jenna Bradley

Jonathan Cowan

Jessica Di Gesso (with Colin Kay)

Dr Ildefonso Rodriguez Ramiro

Patricia de Souza Fonseca

Dr Rosemary Norton

Dr Jason Kerr 

Dr Tony Blake

Lydia Wherry

Doroti Codoni

Krishna Yalamanchili

Gabriela Melo

Holly White

Siraj Anwar (visiting from U Messina)

Dr Adrian Churchman

Dr Stuart Rushworth

Dr Emma McCarthy

Dr David Hughes

Dr Richard Ogborne 

Katy Everett

Lindsay Bentley

Charles Charalambos

Prof Kanthi MS (Visiting Prof from U Malaya)

Prof Maria Miranda Sanz (from U CEU, Spain)

 





Lydia, Krishna, Holly, Maria and Rosemary
 

External Activities and Indicators of Esteem

Learned Societies

  • Chair of Biochemical Society's Theme Panel VI (Biological Systems) since 2013, previously Vice Chair and committee member since 2008 
  • Member of Biochemical Society Council
  • Secretary and co-founder of the British Society for Immunology's East Anglian Regional Group since 2009
  • Treasurer of the British Society for Immunology's Nutritional Affinity Group and member since 2008
  • Member of the Nutrition Society since 1989
  • Member of the Biochemical Society since 1994
  • Member of the British Society for Immunology since 2006
  • Member of the British Pharmacological Society since 2016

 

Reviewer

  • Core Member of BBSRC Committee C  and previous member of BBSRC Pool of Experts
  • Reviewer for grant awarding bodies in the UK (BBSRC, MRC, CRUK, World Cancer Research Fund, North West Cancer Research, Asthma Foundation, Biochemical Society) and in European countries including the Academy of Finland and the Portuguese Science and Technology Foundation
  • Regular referee for several international and national journals in immunology, biochemistry, pharmacology, vascular biology and nutrition

 

Conference Organiser

  • "The Keap1/Nrf2 Pathway in Health and Disease", Biochemical Society Focused Meeting, Robinson College, Cambridge, 6-8 January, 2015
  • "Protein Kinase C Signalling in Health and Disease", Biochemical Society Focused Meeting, Science Gallery, Trinity College, Dublin, Ireland, 24-25 June, 2014
  • "Nutrient Mechanisms in Inflammation, Infection and Immunity” Joint Biochemical Society/ British Society for Immunology Hot Topic Meeting, Charles Darwin House, London, January 2013
  • 2nd "Inflammation and Immunology" Early Careers Symposium, British Society for Immunology East Anglian Regional Group, University of East Anglia, Norwich, March 2013
  • “Nrf2 Signalling in Health and Disease” Biochemical Society Hot Topic Meeting, Charles Darwin House, London, December 2011
  • 1st "Inflammation and Immunology" Early Careers Symposium, British Society for Immunology East Anglian Regional Group, University of East Anglia, Norwich, June 2011
  • Inaugural East Anglian Regional Group Symposium, British Society for Immunology East Anglian Regional Group, University of East Anglia, Norwich, March 2010
  • "Norwich Research Park Inflammation and Immunology" Symposium, University of East Anglia, Norwich, December 2008

 

Expert Panels

  • Consultant for pharmaceutical companies
  • Invited member of consensus group on Micronutrient Deficiencies, University of Hohenheim, Stuttgart, Germany.
  • Expert panel member at the Dietitians Education in Genetics Workshop (part of Department of Health/Wellcome Trust Project: Education in genetics for health professionals), Wellcome Trust, London.
  • Responses to government consultations on vitamins, minerals and phytochemicals.

 

Other

  • Invited speaker to academic departments, pharmaceutical companies and conferences
  • External examiner for postgraduate PhD, MD and MSc students