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RESEARCH
Our mission
We aim at understanding the multiple phenotypes of innate immune cells, among them, macrophages. It is our
intention to elucidate biochemical signatures of macrophages during onset and resolution of inflammation and to
apprehend their multiple roles in the tumor microenvironment.
Acute and chronic inflammation as well as smoldering inflammation in the tumor microenvironment is relevant for a
number of life threatening diseases, demanding basic and translational-orientated biomedical research in the area of
Pathobiochemistry. We work towards a better understanding of the pathogenesis and therapeutic interventions of
inflammatory conditions and tumor progression.
Background
Onset and resolution of inflammation as well as the pro- versus anti-tumor microenvironment is controlled, at least to
a major extent, by resident and infiltrating immune cells, e.g. macrophages. Their extreme plasticity is shaped by the
ability to sense multiple micro-environmental incoming signals and to deliver a dynamic continuum of output
responses.
We assume that the controlled transition from a classically activated or pro-resolving to an alternatively activated
macrophage phenotype is fundamental to understand how inflammation resolves and why tumors progress towards
malignancy. Basic to this decision making process is the removal of dying cells, i.e. apoptotic cells by macrophages.
Defects in removing cellular debris by myeloid phagocytes prominently adds to the induction and propagation of
inflammation, while in the tumor context apoptotic tumor cells condition macrophages to support tumor growth and
survival.
To comprehend the full dynamic range of macrophage responses during inflammation and in the tumor context we
aim at understanding
- How various incoming signals shape the macrophage phenotype and
- How polarized macrophages communicate with their microenvironment
Specifically, our work seeks to define:
- How chronic hypoxia affects the genomic, proteomic, and metabolomic landscape of macrophages
- How apoptotic cells and signals derived from dying cells shape the macrophage phenotype. This includes
lipid mediators (sphingosine-1-phosphate), miRNAs, and cytokines (IL-38)
- How lipid metabolizing enzymes (ALOX5, ALOX15, mPGES1, PTDSS1, ACLY) regulate macrophage
biology
- How the tumor microenvironment controls translation and the ability of macrophages to store or release iron
Synopsis of Research Themes
Funding (over the last years is provided by):
- Deutsche Forschungsgemeinschaft
(Collaborative Research Centers, Graduate Schools, individual funding)
- Deutsche Krebshilfe
- Wilhelm-Sander-Stiftung
- LOEWE (Landes Offensive zur Entwicklung Wissenschaftlich-ökonomischer Exzellenz)
- Industry
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