Dr Polak’s research interest is focused on the mechanisms of regulation of immune responses by human tissue resident dendritic cells (DCs). To be able to investigate the biology of human cutaneous DCs, she has optimized the methods for isolation of viable and functional DC subsets from different human skin compartments. Employing a variety of approaches, including in vitro analysis of DC and T cell phenotype and function, transcriptome network reconstruction and in silico modelling Dr Polak investigates the individual roles of these cell types in regulation of human cutaneous immune responses and molecular mechanisms underpinning their function.
Targeting human Langerhans cells to induce long-lasting tolerance in allergy.
Allergy is a chronic disease that is expected to affect more than 50% of all Europeans in 10 years' time. Recent studies demonstrate, that skin can be successfully used as a gateway for therapeutic interventions, aimed at improving the body's immune defences. Such interventions on the skin would create an attractive strategy in allergy treatment and prevention, but we need to understand better how the immune responses are regulated in human skin.
Applying systems immunology approaches, we aim to address the following questions:
1) Is ability to induce tolerance impaired in atopic skin?
2) How is the allergen presentation regulated in human skin during allergen exposure?
3) How can we target the transcriptional networks in human dendritic cells in order to induce long-lasting allergen tolerance?
Other areas of research –
Iterative development of an experimentally validated, in silico model of signal integration in human tissue-residing dendritic cells.
To apply the advanced computer analysis approach in investigations of complexity of the regulation of cutaneous and systemic immunity by skin DCs Dr. Polak set up collaboration with Prof Tom Freeman (Roslin Institute, Edinburgh). As part of this collaboration, she has undertaken training in a systems biology approach to microarray data analysis in Prof. Freeman laboratory. Comparative analysis of whole transcriptomes of human skin DCs matured in different microenvironmental conditions allowed her to identify molecular switches, including a network of transcription factors and protein kinases, which regulate immunostimulatory potential of DCs. The current goal is to use a systems biology approach to develop a comprehensive in silico model of the key pathways and co-regulated genes critical to cutaneous DC regulation of immune responses.
Development of novel in vitro diagnostic tests for drug hypersensitivity
Type IV hypersensitivities to medicines are the commonest type of drug allergy and severe cases can be fatal. Currently no diagnostic tests are routinely available to confirm the diagnosis or help identify which drug caused a reaction so that the medication can be avoided in the future.
Responding to the clinical need, together with Dr. Mike Ardern-Jones we are developing an in vitro test for diagnosis of acute drug hypersensitivity reactions. Our recent work demonstrated that drug stimulated expression of IL-4 and IFN-g by ELISpot is a rapid, sensitive and convenient diagnostic test for drug allergy in a clinically heterogeneous population typical of routine clinical practice. Further development of these rapid non-radioactive in vitro assays for routine use will provide a significant advancement in management of patients suffering from drug reactions.
Clinical and Experimental Sciences Academic Units
Dr Marta Ewa Polak
Tel: +44 (0)23 81 205727 Email: email@example.com
Room Number: SGH/LE59/MP813
Telephone: (023) 8120 5727