Characterising the cellular contribution to COVID related immunity and immunopathology

Cellular Immunity Team

Menna Clatworthy

Professor Clatworthy’s group research is focused on understanding the regulation of antibody generation and effector function, novel methods of targeting humoral immunity in transplantation and autoimmunity and the role of tissue-environment in shaping resident immune cell activation and function.

The Professor is also an active participant in the Human Cell Atlas Project, utilizing single cell technologies to better understand the cellular landscape of the human kidney.

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Christoph Hess

We aim to understand the molecular metabolic underpinnings of immune cell (dys-)function, and how the metabolic environment impacts on immune cell metabolism and function.

Immune cells defend the body against invading microbes, including SARS-CoV-2. Overshooting immune cell activation can, however, be detrimental – which has been suggested to cause severe COVID-19. In this project we wish to investigate whether dysregulated cellular metabolism elicits disease by driving inadequate inflammation in severe COVID-19. To that end we will examine how metabolic gene variants, plasma metabolites and immune cell dysfunction relate at the molecular level in severe vs. non-severe COVID-19. This work has potential to identify the immunometabolic underpinning of severe COVID-19 – and thereby pinpoint new therapeutic targets.

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James Lee

CD8 T-cells are critical for clearing viral infections, and are specifically depleted in COVID-19 – with the extent of depletion directly correlating with worse outcomes. In an animal model of previous severe respiratory coronavirus infection, infusion of virus-specific T cells was able to protect from lethal viral infection.

Moreover, the recovery of CD8 T cells in patients’ blood has been shown to immediately precede clinical recovery. Our group is employing methods that we have previously optimised for CRISPR-editing primary immune cells to investigate whether it is possible to engineer a CD8 T cell that can recognise SARS-CoV-2 and could form the basis of a novel cell-based therapy to prevent severe disease in high risk patients.

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Paul Lyons

My long-term research interest has been in understanding the genetic and molecular underpinnings of chronic immune disease. More recently, together with Ken Smith, we have run a translational research programme that uses an integrative analytical approach to gain insight into the drivers of disease manifestation and progression across a broad range of immune-mediated diseases.

Ken Smith

The Smith Lab works on the regulation of the human immune system in the context of immune-mediated disease. The hypothesis-generating resources that they have developed include a large transcriptomic dataset from patients with a range of autoimmune and inflammatory diseases, a Europe-wide vasculitis cohort (through foundation of the European Vasculitis Genetics Consortium), and a nationwide collaboration focussed on Primary Immunodeficiency.

Recent discoveries include new pathways underpinning prognosis in immune-mediated diseases (leading to prognostic tests used in the clinic), the genetic definition of subsets of systemic vasculitis, and the discovery of a number of new genetic causes of Primary Immune Deficiency.

James Thaventhiran

Inhibitors of immune checkpoints (ICP) have revolutionised cancer treatment, leading to durable treatment responses in a proportion of patients suffering from previously incurable cancers. The efficacy of this class of drugs is dependent on their ability to trigger the patient’s cytolytic CD8+ T cells targeting tumour cells. However, the broad immune stimulatory capacity of ICP-blockade is associated with a high rate of immune related (irAE).

The unpredictability of both efficacy and AEs in response to these agents is a growing concern. There are limited data relating to this heterogeneity of response and the development of irAE following administration of these agents.

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