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Dr Emily L WilliamsPhD, BSc (Hons)

Senior Research Associate

Emily Williams

Dr Emily L WilliamsPhD, BSc (Hons)

Senior Research Associate

Member of

Research interests

Current research:

  • Developing an antibody drug conjugate for selective calcineurin inhibition of T-cells for the treatment of corticosteroid resistant autoimmune diseases.
  • Investigating the role of monocyte subsets in human inflammatory disease and response to synthetic glucocorticoid steroids.
  • Facilitating other research projects meeting the research objectives of the National Institute of Health Research (NIHR) Biomedical Research Centre (BRC) for Ophthalmology and the UNITE human ocular immunology consortium. 

Antibody-drug conjugate:

Building on our previous published research (https://www.pnas.org/content/112/13/4080) where we have discovered a key subset of immune cells that are not only key to the development of autoimmune disorders, but are specifically resistance to conventional, systemic treatments. We have discovered a key cell-surface protein that can identify these cells and alongside this, we have shown clinically approved drugs (calcineurin inhibitors) can suppress their pathogenic activity. We aim to bring these two elements together to design a targeted drug delivery system, known as an antibody-drug-conjugate (ADC), to specifically bind to these cells (via an antibody against the cell surface protein) and deliver the drug only to these cells, thus avoiding systemic side-effects. The cells we are targeting are part of long-term immune memory and our therapy aims to disarm and render inactive these cells and potentially delete them entirely, whilst retaining an individual’s ability to mount new immune responses to infection. Using this method, we aim to reset the disease causing arm of a patient’s immune system. To achieve this with have partnered with experts in both antibody production (LifeArc) and drug conjugation (Abzena Plc and UCL, School of Pharmacy) and are currently well on our way to generating a functional antibody-drug conjugate to test in our optimised cell culture platforms.

 Human Monocyte Subsets: 

Circulating monocytes are part of the innate immune system and primarily detect, capture and process invading non-self-pathogens and as such can interact with parts of the adaptive immune system, such as T helper cells. By acting as antigen presenting cells to activate T cells during inflammatory conditions and by secreting cytokines which shape T cell differentiation monocytes may contribute to the detrimental immune skew observed in many autoimmune conditions. Monocyte heterogeneity has long been recognised and a specific subset of these (the, CD14++CD16+ intermediate monocytes) are of clinical interest as they are expanded in many inflammatory and autoimmune conditions, including, as we have recently reported, in non-infectious uveitis (http://www.jimmunol.org/content/194/11/5150.long). Glucocortociods (or steroids) are the first line therapeutic for many autoimmune and autoinflammatory diseases.  In vitro steroid treatment of monocytes from healthy donors induces an up-regulation of transcripts associated with an anti-inflammatory phenotype. Alongside this, in the context of inflammatory conditions, steroid treated ex-vivo monocytes have shown enhanced survival, phagocytosis and chemotaxis and displayed an anti-inflammatory phenotype. However, the in vivo action of steroids on human monocytes in autoimmunity, and the consequences of this for T-cell responses, has not yet been fully investigated. This project aims to delineate the processes of steroid-responsiveness in human monocyte subsets and investigate how dysfunction in this could contribute to steroid resistance in autoimmune patients.

 

 

 

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Postal address:
Biomedical Sciences Building
University Walk
Bristol
United Kingdom