A joint venture between the Department of Biology and The Hull York Medical School

Profile

Biography

Dimitris Lagos joined the Centre for Immunology and Infection as a Lecturer in Immunology in January 2011. He obtained his BSc in Chemical Engineering from the National Technical University of Athens (Greece) and his PhD in Immunology from the University of Sheffield (UK). During his PhD, which was part of a Training and Mobility for young Researchers (TMR) European Union Programme, he worked in AstraZeneca (UK) and the Biochemical Institute in the University of Zurich (Switzerland). After his PhD, he joined as a post-doctoral fellow the Cancer Research UK Viral Oncology Group at the Wolfson Institute for Biomedical Research in University College London. In 2008, he became a co-principal investigator and moved with the rest of the Group to UCL Cancer Institute where he developed a strong interest in the complex mechanisms that govern gene expression and the emerging field of non-coding RNAs.

Career

• National Technical University of Athens
  BSc in Chemical Engineering

• University of Sheffield
  PhD in Immunology

• University College London
  Post-doctoral researcher

• University of York
  Lecturer in Immunology

Research

Overview

• MicroRNA and RNA-binding protein expression and function in health and disease
• Endothelial cell biology 
• Gene networks in immunity and cancer

Current projects

MicroRNA Biology

Our laboratory investigates fundamental molecular mechanisms underlying cellular responses to infectious, oncogenic, and differentiation stimuli, focussing on microRNAs, a class of small non-coding RNAs, which predominantly suppress expression of protein-coding genes. Studying the role of microRNAs holds great promise with regards to discovering novel therapeutics and diagnostics for the treatment of infectious diseases, immunopathologies and cancer.

The common theme between the above-mentioned responses is the induction of a dynamic, temporally regulated gene expression programme that is controlled at multiple levels resulting in the formation of complex networks. Our overarching hypothesis is that microRNAs and their associated RNA-binding proteins are essential components of these regulatory networks.

To achieve our goals, we follow an approach that combines the use of human primary cell culture models with studies in experimental disease models. In particular, we use the endothelial cell as our archetypical cellular system, making our findings relevant to a wide range of diseases characterised by aberrant function of the lymphatic and/or vascular system, such as cancer and chronic inflammatory conditions. Our experimental portfolio encompasses hypothesis-driven functional genomic screens, in-depth molecular and cellular biology mechanistic studies, and computational biology approaches (see York Computational Immunology Lab).

The group is funded by The Wellcome Trust (CIDCATS PhD Training Program and Centre for Chronic Diseases and Disorders), The Royal Society, and Yorkshire Cancer Research.

Research group(s)

• Lagos research group (Immunology)

Dimitris Lagos

Matthew Warner

Johnny Leonov

Publications

Selected publications

• Bridge G, Monteiro R, Henderson S, Emuss V, Lagos D, Georgopoulou D, Patient R, Boshoff C. Blood (2012) The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis [Epub ahead of print].
• Westrop SJ, Lagos D, Boshoff C, Bowe M, Imami (2012) African ancestry and innate immunity contribute to the incidence of multicentric Castleman's disease in HIV-1/Kaposi's sarcoma herpesvirus-coinfected individuals, Future Virology, Volume 7, Number 7, July, pp. 729-734(6).
• Gooding M, Tudzarova S, Worthington RJ, Kingsbury SR, Rebstock AS, Dube H, Simone MI, Visintin C, Lagos D, Quesada JM, Laman H, Boshoff C, Williams GH, Stoeber K, Selwood DL. (2011) Exploring the Interaction Between siRNA and the SMoC Biomolecule Transporters: Implications for Small Molecule-Mediated Delivery of siRNA. Chem Biol Drug Des. Oct 8. doi: 10.1111/j.1747-0285.2011.01249.x.

• Yogev O, Lagos D. (2011) Noncoding RNAs and cancer. Silence. Sep 29;2(1):6.
• Lagos D, Pollara G, Henderson S, Gratrix F, Fabani M, Milne RS, Gotch F, Boshoff C (2010) miR-132 regulates antiviral innate immunity through suppression of the p300 transcriptional co-activator Nature Cell Biology May;12(5):513-9.
• James V, Zhang Y, Foxler DE, de Moor CH, Kong YW, Webb TM, Self TJ, Feng Y, Lagos D, Chu CY, Rana TM, Morley SJ, Longmore GD, Bushell M, Sharp TV (2010) LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-mediated gene silencing Proc Natl Acad Sci U S A. Jul 13;107(28):12499-504.
• Hansen A, Henderson S, Lagos D, Nikitenko L, Coulter E, Roberts S, Gratrix F, Plaisance K, Renne R, Bower M, Kellam P, Boshoff C (2010) KSHV-encoded miRNAs target MAF to induce endothelial cell reprogramming Genes Dev. Jan 15;24(2):195-205.
• Emuss V, Lagos D, Pizzey A, Gratrix F, Henderson SR, Boshoff C (2009) KSHV manipulates Notch signaling by DLL4 and JAG1 to alter cell cycle genes in lymphatic endothelia PLoS Pathog. Oct;5(10):e1000616.
• Lagos D, Vart RJ, Gratrix F, Westrop SJ, Emuss V, Wong PP, Robey R, Imami N, Bower M, Gotch F, Boshoff C (2008) Toll-like receptor 4 mediates innate immunity to Kaposi sarcoma herpesvirus Cell Host Microbe Nov 13;4(5):470-83.
• Lagos D, Trotter MW, Vart RJ, Wang HW, Matthews NC, Hansen A, Flore O, Gotch F, Boshoff C (2007) Kaposi sarcoma herpesvirus-encoded vFLIP and vIRF1 regulate antigen presentation in lymphatic endothelial cells Blood Feb 15;109(4):1550-8.
• Wang HW, Trotter MW, Lagos D, Bourboulia D, Henderson S, Mäkinen T, Elliman S, Flanagan AM, Alitalo K, Boshoff C (2004) Kaposi sarcoma herpesvirus-induced cellular reprogramming contributes to the lymphatic endothelial gene expression in Kaposi sarcoma Nature Genetics Jul;36(7):687-93.
• Bourboulia D, Aldam D, Lagos D, Allen E, Williams I, Cornforth D, Copas A, Boshoff C (2004) Short- and long-term effects of highly active antiretroviral therapy on Kaposi sarcoma-associated herpesvirus immune responses and viraemia AIDS Feb 20;18(3):485-93.
• Cesaro-Tadic S, Lagos D, Honegger A, Rickard JH, Partridge LJ, Blackburn GM, Plückthun A (2003) Turnover-based in vitro selection and evolution of biocatalysts from a fully synthetic antibody library Nature Biotechnology Jun;21(6):679-85.

External activities

Memberships

• British Society for Immunology (BSI)
  Member
• Biochemical Society
  Early Career Member

Teaching

Undergraduate

• Hull York Medical School
  Block 1 Lead
  Two plenary lectures (Block 1) in gene expression
  SSC in Infectious Diseases (Year 2 only)
• Biology/Biochemistry
  Three lectures in virology (Year 1)
  Term 2/3 tutorial module on RNA in Disease (Year 1)
  Project student (Final Year) supervision

Postgraduate

• PhD student supervision
  
• CIDCATS PhD Training Programme
  Term 1 core project coordinator
  Tutorial on gene expression regulation
• MSc in Post Genomic Biology
  Internal project supervisor