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The William Harvey Research Institute - Barts and The London

Dr Lucy Norling

Senior Lecturer & Versus Arthritis Senior Fellow

Centre: Microvascular Research

Email: l.v.norling@qmul.ac.uk
Telephone: +44(0) 20 7882 5644

Profile

Lucy Norling graduated with a Masters in Research and PhD from the William Harvey Research Institute, Queen Mary University of London in 2008. Her research focused on galectin-1; an endogenous regulator of inflammatory resolution. Dr. Norling was then awarded a 3 year Arthritis Research UK Foundation Fellowship to study the generation and bioactions of novel lipid mediators derived from omega-3 fatty acids and spent two years training at Harvard Medical School, Boston, with the mentorship of Professor Charles Serhan.

In 2012 Dr Norling attained a 5 year Arthritis Research UK Career Development Fellowship to investigate the protective actions of omega-3 fatty acid derived specialized pro-resolving lipid mediators (SPM) in inflammatory arthritis. SPM provide a molecular mechanism for the beneficial effects of fish oil supplementation in patients with arthritis, and offer novel therapeutic approaches to treat inflammatory diseases.

In 2019 Dr Norling was awarded a 5 year Versus Arthritis Senior Fellowship entitled “Reprogramming Resolution in the Arthritic Joint”. Her current research aims to determine whether inflammatory joint diseases persist due to an inadequate synthesis of SPM and explores how SPM protect and repair joint tissue.

Research

Group members

Hannah Law, Silvia Oggero, Shani Austin-Williams, Chiara Cecconello, Michele Padaovan.

Summary 

Our understanding of how the inflammatory process is terminated has evolved, with the appreciation that protective mediators actively resolve inflammation. The discovery of omega-3 fatty acid derived specialized pro-resolving lipid mediators (SPM) provides a molecular mechanism for the beneficial effects of fish oil supplementation in patients with arthritis, and offer novel therapeutic approaches to treat inflammatory diseases. Supported by my Foundation Fellowship, I demonstrated that SPM inhibit PMN-endothelial interactions, dampen acute inflammation, and help fight infection. During my Career Development Fellowship I investigated the bioactions of SPM in experimental arthritis and found that resolvin D1 limits joint leukocyte infiltration, arthritis severity and protected from cartilage damage. We also determined that production of specific SPM including resolvin D3 is dysregulated in experimental arthritis, and that local SPM within murine joints can be modulated by omega-3 dietary supplementation.

There is a clear need to develop new innovative therapeutic agents for arthritis that can both reduce the inflammation that drives disease AND initiate tissue repair and regeneration. With the support of a Versus Arthritis Senior Fellowship I aim to establish how SPM reprogram innate immune cells and stromal cells within the joint tissue to switch on repair mechanisms that temper the aggressive and inappropriate behaviour of cells within the joint tissue to ultimately protect the cartilage from erosion. The overarching goal of our research is to establish novel leads for the restoration of joint function to ultimately limit disability and improve the lives of patients with arthritis.

Key Publications

ORCID https://orcid.org/0000-0001-5316-9115 

  • Rhys HI, Dell'Accio F, Pitzalis C, Moore A, Norling LV*, Perretti M*. Neutrophil Microvesicles from Healthy Control and Rheumatoid Arthritis Patients Prevent the Inflammatory Activation of Macrophages. EBioMedicine. 2018 Mar;29:60-69. (*share senior authorship).
  • Perretti M, Cooper D, Dalli J, Norling LV. Immune resolution mechanisms in inflammatory arthritis. Nat Rev Rheumatol. 2017 Feb;13(2):87-99.
  • Arnardottir HH, Dalli J, Norling LV, et al. Resolvin D3 is Dysregulated in Arthritis and Reduces Arthritic Inflammation. J Immunol. 2016 Sep 15;197(6):2362-8. 
  • Norling LV, Headland SE, Dalli J, Arnardottir HH, Haworth O, Jones HR, Irimia D, Serhan CN, Perretti M. Pro-resolving and cartilage-protective actions of resolvin D1 in inflammatory arthritis. JCI Insight. 2016 Apr 21;1(5):e85922.
  • Headland SE, Jones HR, Norling LV, Kim A, Souza PR, Corsiero E, Gil CD, Nerviani A, Dell’Accio F, Pitzalis C, Oliani SM, Jan LY, Perretti M. Neutrophil-derived microvesicles enter cartilage and protect the joint in inflammatory arthritis. Science Translational Medicine 2015, Nov 25;7(315):315ra190.
  • Headland SE, Jones HR, D'Sa AS, Perretti M, Norling LV*. Cutting-edge analysis of extracellular microparticles using ImageStream(X) imaging flow cytometry. Sci Rep. 2014 Jun 10;4:5237. *Senior authorship.
  • Norling LV, Dalli J, Flower RJ, Serhan CN, Perretti M. Resolvin D1 Limits Polymorphonuclear Leukocyte Recruitment to Inflammatory Loci: Receptor-Dependent Actions. Arterioscler Thromb Vasc Biol . 2012 Aug;32(8):1970-8.
  • Dalli J, Montero-Melendez T, Norling LV, et al. Heterogeneity in neutrophil microparticles reveals distinct proteome and functional properties. Mol Cell Proteomics . 2013 Aug;12(8):2205-19.
  • Norling LV, Spite M, Yang R, et al. Humanized nano pro-resolving medicines limit inflammation and enhance wound healing. J Immunol. 2011 May 15;186(10):5543.
  • Spite M, Norling LV, Summers L, et al. Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis. Nature. 2009 Oct 29;461(7268):1287-91. 

Collaborators

Internal

External

  • Prof. Charles Serhan, Brigham & Women’s Hospital & Harvard Medical School, USA
  • Dr. Daniel Irimia, Massachusetts General Hospital, Boston, USA
  • Prof. Philippa Hulley, NDORMS, University of Oxford