Marta Polak - Fellowship Sir Henry Dale Fellowship Targeting human langerhans cells to induce long-lasting tlearance in alleargy

Project overview

Skin is the largest body organ, and a major site for allergic disease, such as atopic dermatitis. We and other have demonstrated, that skin contact with allergens can induce and worsen allergic responses. In contrast, 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 understan d better how the immune responses are regulated in human skin. Recent findings point to the critical role of a subset of immune cells in the outermost layer of the skin, called Langerhans' cells (LCs), in the orchestration of immune responses. It is proposed, to investigate the molecular mechanism of immune regulation by human LCs isolated from allergic and healthy individuals. Identified candidate molecular regulators will then be switched off using small molecular inhibitors, to investigat e their suitability as therapeutic targets. By focusing on a key control element in human skin this comprehensive approach will lead to identification of novel therapeutic strategies for induction of long-lasting tolerance in allergy.

Research outputs

Potential biomarker identification by RNA-seq analysis in antibiotic-related drug reaction with eosinophilia and systemic symptoms (DRESS)

Ying Xin Teo, Wei Yann Haw, Andreas Vallejo, Carolann McGuire, Jeongmin Woo, Peter Simon Friedmann, Marta Ewa Polak & Michael Roger Ardern-Jones, 2022, Toxicological Sciences, 189(1), 20-31

DOI: 10.1093/toxsci/kfac062

Type: article

Integrated transcriptomic analysis of human tuberculosis granulomas and a biomimetic model identifies therapeutic targets

Michaela T. Reichmann, Liku Bekele Tezera, Andres Vallejo Pulido, Milica Vukmirovic, Rui Xiao, James Reynolds, Sanjay Jogai, Susan Wilson, Benjamin Marshall, Mark Jones, Alasdair Leslie, Jeanine M. D'Armiento, Naftali Kaminski, Marta Polak & Paul Elkington, 2021, Journal of Clinical Investigation, 131(15), 1-16

DOI: 10.1172/JCI148136

Type: article

Dual Dean entrainment with volume ratio modulation for efficient droplet co-encapsulation: extreme single-cell indexing

Jack Harrington, Luis Blay Esteban, Jonathan Butement, Andres F. Vallejo, Simon I.R. Lane, Bhavwanti Sheth, Maaike S.A. Jongen, Rachel Parker, Patrick S. Stumpf, Rosanna C.G. Smith, Ben D. MacArthur, Matthew J.J. Rose-Zerilli, Marta E. Polak, Tim Underwood & Jonathan West, 2021, Lab on a Chip, 17(21), 3378-3386

DOI: 10.1039/d1lc00292a

Type: article

An IRF1-IRF4 toggle-switch controls tolerogenic and immunogenic transcriptional programming in human Langerhans cells

James Davies, Andres F. Vallejo, Sofia Sirvent, Gemma Porter, Kalum Clayton, Yamkela Qumbelo, Patrick Stumpf, Jonathan West, Clive Gray, Nyaradzo Chigorimbo-Murefu, Benjamin Macarthur & Marta Polak, 2021, Frontiers in Immunology, 12

DOI: 10.3389/fimmu.2021.665312

Type: article

Machine learning applied to atopic dermatitis transcriptome reveals distinct therapy‐dependent modification of the keratinocyte immunophenotype

Kalum Clayton, Andres Vallejo Pulido, Sofia Sirvent Bernal, James David Davies, Gemma Douilhet, Isabel Reading, Fei Ling Lim, Michael Ardern-Jones & Marta Polak, 2021, British Journal of Dermatology, 184(5), 913–922

DOI: 10.1111/bjd.19431

Type: article

Resolving cellular systems by ultra-sensitive and economical single-cell transcriptome filtering

Andres F. Vallejo, James Davies, Amit Grover, Ching-hsuan Tsai, Robert Jepras, Marta E. Polak & Jonathan West, 2021, iScience, 24(3), 102147

DOI: 10.1016/j.isci.2021.102147

Type: article

Ileal transcriptomic analysis in paediatric Crohn's disease reveals IL17- and NOD-signalling expression signatures in treatment-naïve patients and identifies epithelial cells driving differentially expressed genes

James John Ashton, Konstantinos Boukas, James David Davies, Imogen Sian Stafford, Andres Vallejo, Rachel Haggarty, Tracy Antonio Francisco Coelho, Akshay Batra, Nadeem A. Afzal, Bhumita Vadgama, Anthony Williams, R. Mark Beattie, Marta Polak & Sarah Ennis, 2020, Journal of Crohn's and Colitis, 15(5), 774-786

DOI: 10.1093/ecco-jcc/jjaa236

Type: article