Personal profile

Biography

Dr. John Grainger obtained his BSc in Molecular Biology from University College London in 2004. Following this, he undertook his MRes and PhD at the University of Edinburgh on the Wellcome Trust funded Molecular Basis of Disease programme. The focus of his PhD work was exploring mechanisms used by gastrointestinal worms to modulate the host's adaptive immune system in order to improve their own survival. As part of these studies he identified a novel mechanism by which helminths secrete TGF-β homologues to suppress the inflammatory response. After his PhD John moved in 2009 as a visiting research fellow to the Laboratory of Parasitic Diseases at the National Institutes of Health (NIH), USA, where he developed an interest in novel functions of immune cell populations during infection. His recent studies have predominantly focused on understanding innate cell responses towards the commensal microbiota during acute pathogen infection.

Research interests

Monocytes and Intestinal Parasites

Monocytes and neutrophils are the dominant cell populations recruited to sites of infection and injury. Exploring the function of these cells and how their activities are conditioned in diverse tissue microenvironments is critical to improved understanding of inflammatory processes. Using cutting-edge in vitro and in vivo techniques I employ well-characterized infections to probe the full-spectrum of activation of these cell types with particular focus on the gastrointestinal tract. Given that aberrant activation of monocytes and neutrophils is associated with multiple inflammatory disorders improved knowledge of the cellular and molecular mechanisms modulating their functions could lead to novel therapeutic targets.

In my recent studies I have identified a previously undescribed mechanism by which monocytes are able to directly modulate neutrophil activation. In particular I have shown that during acute gastrointestinal infection monocytes produce the lipid mediator prostaglandin E2 (PGE2) that plays a critical role in limiting highly pathologic neutrophil activation and prevents life-threatening gastrointestinal inflammation. This activity was specific to the gastrointestinal tract and was in part dependent upon signals derived from the commensal flora. This finding is of particularly high clinical relevance as commonly used non-steroidal anti-inflammatory drugs (NSAIDs) act by limiting cyclooxygenase (COX) activity, a rate-limiting enzyme in PGE2 production.

A major current goal of my research is to understand how these novel regulatory features are acquired. In recent years much research has been focussed upon understanding how tissue specific signals condition the function of recruited cell populations. Intriguingly, in this setting I have found that signals released systemically are needed to condition inflammatory cells during differentiation in order to induce this regulatory phenotype. Indeed, regulatory function is acquired by these cells prior to exit from the bone marrow. This sheds light on a poorly explored process of inflammatory cell differentiation during infection in which systemic signals programme eventual function toward local cues in tissue. Better understanding of how systemic and local cues act in tandem to condition inflammatory cell function could lead to new opportunities for manipulating their function for therapeutic purposes.

 

 

 

My group

Rossana Azzoni - PhD Student

Hayley Bridgeman - Research Technician

Rufus Daw - PhD Student

Ian Prise - Postdoctoral Researcher

Tovah Shaw - Postdoctoral Researcher

Kelly Wemyss - PhD Student

Thomas Williams - PhD Student

Mehwish Younas - Postdoctoral Researcher

Kara Filbey - Postdoctoral Researcher

Verena Kaestele - Postdoctoral Researcher

Ruth Stephens - PhD Student

Office hours

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Expertise related to UN Sustainable Development Goals

In 2015, UN member states agreed to 17 global Sustainable Development Goals (SDGs) to end poverty, protect the planet and ensure prosperity for all. This person’s work contributes towards the following SDG(s):

  • SDG 2 - Zero Hunger
  • SDG 3 - Good Health and Well-being

Areas of expertise

  • QR180 Immunology

Research Beacons, Institutes and Platforms

  • Lydia Becker Institute

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