Dr Dimitris Lagos

Senior Lecturer in Immunology

Overview

Non-coding RNA Immunobiology Group

Non-coding RNA (ncRNA) transcripts are remarkably more prevalent in mammalian genomes when compared to other species. It has been proposed that this is functionally linked to the increased complexity of mammals. This increased complexity is undoubtedly also reflected in the mammalian immune system. Our work is built around the central proposition that studying the function of non-coding RNAs in the immune system can provide critical insight into both immunity and non-coding RNA biology. The overarching working hypothesis of our work is that modulation of immune responses is a key function of non-coding RNAs in mammals and that coordination of the machineries that control non-coding and coding RNA metabolism is required for optimal mammalian immunity. Currently, there are three main themes of research in the group:

1. ncRNA functions in the immune system: What do ncRNAs do?


The ultimate demonstration of physiological relevance for any gene is genetic testing of its function at the whole organism level. The central driver of our work is to test the function of miRNAs and lncRNAs in vivo. Recent findings and current work focus on the role of individual miRNAs or lncRNAs in T cell activation and effector functions and myeloid cell activation in models of pathogen induced chronic inflammation. In parallel, we are investigating the role of the non-coding genome in the function of immune checkpoints in a wide range of cellular contexts.

2. ncRNA mechanism of action: How do ncRNAs work?

We investigate mechanisms of RNA/protein interaction that are responsible for the function of small and long ncRNAs (miRNAs and lncRNAs, respectively) in the immune system. Recent discoveries include signalling pathways that regulate miRNA biogenesis and silencing complex formation. Current studies focus on RNA-binding proteins that associate with miRNAs and lncRNAs in cells responding to infectious or inflammatory stimuli.

3. ncRNAs as disease biomarkers: How can we use ncRNAs in the clinic?

The group is developing pipelines that translate functional genomics into routine blood tests used for patient stratification and rational use of antibiotics and biologics. Recent and current work focuses on skin inflammation.

pipelines that translate functional genomics into routine blood tests

 

‌Recent research highlights

Yee et al., MicroRNA-155 induction via TNF-α and IFN-γ suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells. Journal of Biological Chemistry. 2017 Dec 15;292(50):20683-20693.

Heyam et al., Conserved asymmetry underpins homodimerization of Dicer-associated double-stranded RNA-binding proteins. Nucleic Acids Research. 2017 Dec 1;45(21):12577-12584.

Bridge et al., Argonaute Utilization for miRNA Silencing Is Determined by Phosphorylation-Dependent Recruitment of LIM-Domain-Containing Proteins. Cell Reports. 2017 Jul 5;20(1):173-187.

Warner et al., S6K2-mediated regulation of TRBP as a determinant of miRNA expression in human primary lymphatic endothelial cells. Nucleic Acids Research. 2016 Nov 16;44(20):9942-9955. 

 

Funding

The group is funded by The Medical Research Council, The Wellcome Trust (CIDCATS PhD Training Program and Centre for Chronic Diseases and Disorders), and The BBSRC (DTP in Mechanistic Biology). 

Research Group

NameStatusProject
Nidhi Dey PDRA funded by MRC/GCRF (with Paul Kaye and Pegine Walrad) Leishmaniasis digital pathology network (https://leishpathnet.org/)
Mia Shandell PDRA funded by MRC Confidence in Concept Award (with Will Brackenbury) Immune checkpoint regulation
Daniel Yee BBSRC DTP PhD Student MicroRNAs in lymphatic endothelial cell responses to inflammation.
Shoumit Dey CIDCATS/Wellcome Trust PhD Student ncRNAs in trained immunity
Miles Evans MRes student

Skin inflammation

Sophie Hawkins MRes student miRNA mechanisms of action
Euan Mitchell MRes student lncRNAs in immunity

Teaching and Scholarship

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My teaching in the Hull York Medical School and Department of Biology is inherently connected to my research interests including gene expression regulation in the immune system, host pathogen interactions, and the fundamental principles of molecular cell biology. I am the HYMS Phase 1 Lead for the Scholarship and Special Interest Programme and member of several committees overseeing curriculum development and delivery in both Biology and HYMS.

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Stage 2 Immunology, Stage 3 Principles of Molecular Virology, Stage 3 Mechanisms to Therapies, HYMS Block 1, 4, 9.

 

 

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Basic skills in biological sciences (Stage 1). HYMS SSIP on Host/Pathogen interactions (Phase 1)

 

 

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MicroRNA biology: from mechanism to function 

 

 

Publications


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Contact details

Dr Dimitris Lagos
Senior Lecturer in Immunology
Centre for Immunology and Infection
University of York
Heslington
York
YO10 5DD

Tel: 01904 328930
Fax: 01904 328844