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News: EAS Academy - Lecture of the week

System-level analyses of inflammatory and repair macrophages reveal an integrated circuitry of lip

Monday 11 May 2020   (0 Comments)
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About the presenter: Professor László Nagy

László Nagy is Professor of Biochemistry and Molecular Biology, University of Debrecen (since 2006),
Head of the Center for Clinical Genomics and Personalized Medicine Hungary (since 2000) and Director of Genomic Control of Metabolism Program and Professor of the Diabetes & Obesity, Research Center Sanford Burnham Prebys Medical Discovery Institute at Lake Nona (since 2013).
After completing his medical degree and PhD at the University Medical School, Debrecen, Hungary he undertook postdoctoral research at the University of Texas Medical School, Houston, USA (1992 – 1995).

Subsequent appointments included International Research Scholar of the Howard Hughes Medical Institute (2001-2011), a Wellcome Trust International Senior Research Fellow (2005-2010), and a Fulbright Scholar Visiting Scientist, The Salk Institute for Biological Studies (2010-2011).

His affiliations include the Endocrine Society (USA), American Society of Biochemistry and Molecular Biology, American Association of Immunologists, and the American Physiological Society. He is a founding member of the Hungarian Society for Bioinformatics. 

Professor Nagy is the recipient of numerous awards, most recently the ESCI Award for Excellence in Biomedical Investigation (2008), Academia Europaea (2012), Scientist of the Year 2012 (City of Debrecen, Dehir), and the Béla Tankó prize (2014).

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About the topic

Systems biology provides a holistic collaborative approach when investigating complex cellular processes, integrating data from many scientific areas to predict how these systems change over time and under varying conditions.
A combination of high-throughput, multiplexed, quantitative methods with computational modelling and statistical approaches is required, especially relevant in the context of macrophage function, given the versatility, plasticity and multiple roles of macrophages in the innate immune system.

The rapid re-programming required for the plasticity of macrophage function depends on the changing microenvironment and metabolic processes.
Understanding the transcriptional regulation of macrophage-specific responses to environmental cues has been aided by recent progress in genomics, both for transcriptional activation and, more recently, transcriptional repression.
Mechanistic models that explain how transcription factors control macrophage activation and function provide an interpretative framework for the impact of genetic variability on macrophage-specific gene expression.
Future systems analysis of the regulation of specific genes involved in macrophage activation in response to different stimuli is likely to represent the next frontier for this field.

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Key references
  • Czimmerer Z, Daniel B, Horvath A, Rückerl D, Nagy G, Kiss M, Peloquin M, Budai MM, Cuaranta-Monroy I, Simandi Z, Steiner L, Nagy B Jr, Poliska S, Banko C, Bacso Z, Schulman IG, Sauer S, Deleuze JF, Allen JE, Benko S, Nagy L. The Transcription Factor STAT6 mediates direct repression of inflammatory enhancers and limits activation of alternatively polarized macrophages. Immunity 2018;48:75-90.
  • Czimmerer Z, Horvath A, Daniel B, Nagy G, Cuaranta-Monroy I, Kiss M, Kolostyak Z, Poliska S, Steiner L, Giannakis N, Varga T, Nagy L. Dynamic transcriptional control of macrophage miRNA signature via inflammation responsive enhancers revealed using a combination of next generation sequencing-based approaches. Biochim Biophys Acta 2018;1861:14-28.
  • Czimmerer Z, Nagy ZS, Nagy G, Horvath A, Silye-Cseh T, Kriston A, Jonas D, Sauer S, Steiner L, Daniel B, Deleuze JF, Nagy L. Extensive and functional overlap of the STAT6 and RXR cistromes in the active enhancer repertoire of human CD14+ monocyte derived differentiating macrophages. Mol Cell Endocrinol 2018;471:63-74.

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