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Project
SBO Project : LipoMacs: functional Lipidomics to unlock Macrophage-mediated therapy (FWOSBO48)
Macrophages are increasingly recognized as key regulators of common
diseases such as neurodegeneration, cancer and liver disease. Central to
macrophage functionality is their ability to attain different activation
states, ranging from inflammation-inducing to inflammation-resolving
and healing states. The precise phenotype and functions adopted are
highly context dependent and have been shown to be driven by the local
microenvironment in which the macrophages reside. Emerging evidence
indicates that many pathological conditions are associated with
alterations in macrophage phenotypes/functions due to a shift in their
activation state, however whether this is a result of true macrophage
plasticity or the recruitment of a phenotypically distinct macrophage
population is also disease-specific. Crucially, recent studies have
demonstrated a role for lipids and altered lipid metabolism in regulating
the phenotypes and functions of disease-associated macrophages. In
this project, we bring together unique complementary expertise from
both academia and industry to design strategies for the functional
reprogramming of macrophages by interfering with lipid metabolism. To
this end, and instructed by the real-world needs of the industrial
partners, we will set up a comprehensive technology pipeline involving
state-of-the-art lipidomics approaches to map the heterogeneous
landscape of macrophage phenotypes in terms of lipid metabolism in
healthy and diseased tissue. Using gold-standard preclinical models, we
will identify and validate key enzymes in lipid metabolism as potential
targets and will provide proof of concept of pharmacological and/or
nutraceutical approaches to regulate macrophage functions. This
pipeline can be used for unbiased discovery but also offers multiple
entry points to validate predefined targets in a hypothesis-driven
manner..
diseases such as neurodegeneration, cancer and liver disease. Central to
macrophage functionality is their ability to attain different activation
states, ranging from inflammation-inducing to inflammation-resolving
and healing states. The precise phenotype and functions adopted are
highly context dependent and have been shown to be driven by the local
microenvironment in which the macrophages reside. Emerging evidence
indicates that many pathological conditions are associated with
alterations in macrophage phenotypes/functions due to a shift in their
activation state, however whether this is a result of true macrophage
plasticity or the recruitment of a phenotypically distinct macrophage
population is also disease-specific. Crucially, recent studies have
demonstrated a role for lipids and altered lipid metabolism in regulating
the phenotypes and functions of disease-associated macrophages. In
this project, we bring together unique complementary expertise from
both academia and industry to design strategies for the functional
reprogramming of macrophages by interfering with lipid metabolism. To
this end, and instructed by the real-world needs of the industrial
partners, we will set up a comprehensive technology pipeline involving
state-of-the-art lipidomics approaches to map the heterogeneous
landscape of macrophage phenotypes in terms of lipid metabolism in
healthy and diseased tissue. Using gold-standard preclinical models, we
will identify and validate key enzymes in lipid metabolism as potential
targets and will provide proof of concept of pharmacological and/or
nutraceutical approaches to regulate macrophage functions. This
pipeline can be used for unbiased discovery but also offers multiple
entry points to validate predefined targets in a hypothesis-driven
manner..
Date:1 Oct 2022 → Today
Keywords:Neurological and neuromuscular diseases, Cancer biology, Inflammation, Hepatology (incl. pancreas), Lipids
Disciplines:Neurological and neuromuscular diseases
Project type:Collaboration project