Independent Research Fellow inToxicology (Immunology Grouping), Faculty of Life Sciences
My first degree was Biochemistry (BSc 1st Class; 1980-1984) at Bath University, followed by a PhD in Immunochemistry at Southampton University with Professor George Stevenson focused on developing methods to enhance targetting and destruction of tumour (leukemia) cells by antibody. In 1988 I began my first Post Doc position at the ICI Central Toxicology Laboratory (CTL) at Alderley Edge (funded by Unilever) investigating the immunological mechanisms of allergic reactions caused by chemicals. Although CTL was an industrial laboratory, it had a very academic approach and commitment to basic research and as the company evolved from ICI, to Zeneca, to AstraZeneca and finally to Syngenta, I remained, expanding my role from Post Doc to Head of Immunology with a continued interest in mechanisms of allergic responses. With the closure of CTL, in October 2007 I relocated to the University of Manchester to join a new Toxicology grouping with continued interests in chemical and protein allergy, dendritic cell biology and inflammatory diseases.
In 2003 I was awarded "Young Investigator of the Year" by the Immunotoxicology Specialty Section of the Society for Toxicology and in 2004 I became a member of the Department of Health Committee on the Toxicity of Chemicals in Food, Consumer Products and the Environment. I am on the editorial board of the journals "Food and Chemical Toxicology", "Toxicological Sciences" and "Biomarkers".
My research interests are at the interface between immunology (how our body protects us from infection), allergy (when our immune system is overprotective and causes harm) and toxicology (adverse health effects caused by foreign materials). Allergy is an important disease affecting up to 1 in 10 individuals, and is increasing. Allergy is also the most frequent form of adverse health effect (toxicology) impacting on the immune system. Small reactive chemicals can cause allergic reactions in skin or lung and some proteins can cause asthma or food allergy. The research goals are to understand why only some chemicals and proteins cause allergy, what drives the different types of allergic responses and the cells and molecules involved, including whether preferences for the type of allergic responses can be imprinted on the immune system. One example is whether the pattern of sugar molecules on proteins plays a key role in promoting an allergic response. This research should lead to the development of new and improved methods for the identification and characterisation of allergens, and also provide information about which cells and molecules are important, providing opportunities for new treatments of immune and inflammatory diseases.
My main research interests are at the interface between immunology,allergy and toxicology.
Toxicology is currently within the Immunology Grouping in the Faculty of Life Sciences
Toxicology is the study of the adverse health effects caused by foreign materials (xenobiotiocs); so immunotoxicology is the study of adverse health effects of xenobiotics on the immune system. These adverse effects can suppress the normal ability of the immune system to respond to infection/disease (immunosuppression) or may cause a specific immune response (allergic or hypersensitivity reaction) that itself causes the disease. My research interests are focused on understanding the role of immune cells and molecules in shaping the polarization of allergic responses to chemicals and proteins.
Chemicals are able to cause various forms of allergic disease in susceptible individuals: skin sensitization or chemical respiratory allergy. Using reference skin and respiratory allergens we have demonstrated that different classes of chemical allergen stimulate divergent immune responses characteristic of the development of polarized type 1 and type 2 T lymphocyte subsets; cells that ensure the response is tailored to fit the type of immune challenge experienced. The roles of epidermal Langerhans cells (LC) and other skin dendritic cells (DC), the epidermal cytokine microenvironment and cells of the innate immune system such as Natural Killer cells and gammadelta T cells in determining the quality of immune response induced by chemical allergens is a continuing interest. The site of first interaction of chemical with protein (soluble or membrane-associated) may play a decisive role. For protein allergens, the key question is why is it that only a small minority of proteins that are recognized as foreign (immunogenic) cause allergic reactions? That is, what are the qualities that confer on proteins the ability to cause allergic (generally IgE-mediated) reactions. Two areas of particular interest here are the role of glycosylation and the role of resistance to proteolytic digestion, both extracellularly and intracellularly. There is also increasing evidence that the routes of exposure may play a key role in whether an individual develops food allergic responses or instead becomes "tolerant". Here it is hypothesized that if first exposure is through the skin rather than the gastrointestinal tract, the interactions of LC and other DC with T cells (including Tregulatory cells) predisposes to the development of IgE responses.
A further area of interest the devlopment of novel therapeutics for the treatment of immune and inflammatory skin diseases. The study of the cytokine regulation of LC and dermal DC migration in man and mouse has revealed that there are several endogenous proteins that have immunomodulatory (down-regulatory) effects on cytokine production and hence LC migration. Current investigations are directed towards understanding the molecular bases of these effects and defining the smallest peptide that can recapitulate the effects of the whole protein.