Menno de Winther

De Winther Lab

Prof. Menno de Winther; vice-Chair department

Biosketch

Menno de Winther received his PhD at Leiden University after which he had postdoctoral positions at Oxford University and Maastricht University. Since 2012 he is a full professor in Vascular Immunological Cell Biology at the University of Amsterdam.

Our research focusses on understanding the molecular regulation of monocytes and macrophages in the context of cardiovascular disease. Using state-of-the-art methods, we employ mouse models, cell systems and patient derived materials to study inflammatory regulation, signal transduction pathways and epigenetic processes in monocytes and macrophages. Small molecule drug approaches are applied to develop therapeutically relevant interventions.

In recent years Menno de Winther was a PI and workpackage leader on two large consortium grants from the Netherlands Heart Foundation (CVON-GENIUS1 and GENIUS2), an EU-funded Marie-Curie Innovative Training Network (EPIMAC) and of a transatlantic Leducq network on the role of epigenetics in atherosclerotic disease. He is currently coordinator of a ZonMW grant on epigenetics. He is also an Established Investigator of the Netherlands Heart Foundation.

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De Winther LabProf. Menno de Winther; vice-Chair department

Biosketch

De Winther Lab

Research

Epigenetics

It is increasingly being recognized that epigenetic processes (ie histone modifications, DNA methylation) are dynamically regulated in cells and critically control transcriptional responses in inflammation and immunity.
Our group is investigating the regulation of the epigenetic landscape of monocytes and macrophages in health and disease settings and is evaluating how interventions targeting epigenetic enzymes can be used to control inflammatory responses.

Cytokines and signaling pathways

Cytokines are key drivers in inflammation and immune responses. Through induction of specific signaling pathways they critically determine cellular responses and thereby dictate disease development. Cytokines such as IFNγ, IFNβ or TNF can skew macrophages towards pro-inflammatory, so-called M1, responses which are important for antiviral responses and bactericidal activity. Other cytokines such as IL-4 and IL-13 skew macrophages to a so called alternatively activated program which regulate fibrosis and wound healing. IL-10 is essential for general dampening of macrophage activation and is important for resolution of inflammation.
In our group we try to identify how we can manipulate cytokine responses and downstream signaling pathways to skew macrophages to a atherosclerosis-beneficial phenotype.

Immunometabolism

Recent data shows that cellular energy metabolism is strongly associated with macrophage inflammatory responses. While pro-inflammatory responses are driven by increased glycolysis, an anti-inflammatory macrophage thrives on oxidative phosphorylation. Specific interventions in glycolytic pathways or oxidative phosphorylation strongly influence macrophage activation patterns.
We are performing studies to identify metabolic characteristics that specify macrophage subtypes and interventions to modulate macrophage functioning in disease.

Hyperlipidemia

Atherosclerosis develops in a setting of hyperlipidemia, characterized by elevated levels of LDL- and VLDL-sized particles leading to increased plasma levels of cholesterol. A key hallmark of atherosclerosis is the intracellular accumulation of lipids in macrophages. This feature makes atherosclerosis a unique chronic inflammatory disease, since macrophages are thus functioning in a setting of dysbalanced intra- and extracellular lipid levels.
Our group is studying how lipids regulate macrophage responses in atherosclerosis and can be used to control its behavior in disease.