Publications (link to AU profile)

Title: Targeting microglia-mediated phagocytosis in neurodegenerative diseases via the SIRP⍺-CD47 pathway

My Ph.D. project focuses on microglia, the brain’s resident macrophage, and their role in neurodegenerative diseases.

Similar to macrophages, microglial cells perform phagocytosis where they engulf and destroy foreign or harmful substances. Recent studies suggest that excessive phagocytosis of healthy neurons by stressed microglial cells might contribute to neurodegeneration in brain diseases such as Alzheimer’s disease, Parkinsons disease and Multiple Sclerosis.

Phagocytosis is normally regulated by signals that either promote or inhibit phagocytosis. One particularly important signal, and main focus of the project, is the SIRPalfa-CD47 pathway. This pathway downregulates phagocytosis, thereby protecting neurons from being mistakenly targeted.

Considering this, we have set the following primary goals of the project:

1. To reduce the amount of neurons that microglial cells mistakenly destroy by using lipid nanoparticles containing SIRPalfa-mRNA in which upregulates the neuron-protective SIRPalfa.
2. To investigate SIRPalfa and other signals that regulate phagocytosis as biomarkers to improve the diagnosis and monitoring of neurodegenerative diseases. This will involve studying blood and cerebrospinal fluid samples from individuals diagnosed with neurodegenerative diseases.

With this project, we hope to uncover new disease mechanisms and potentially identify targets for treatment. Additionally, we hope to identify biomarkers of neurodegeneration for future diagnosis and monitoring.

The project is supported by Region Midtjyllands Sundhedsvidenskabelige Forskningsfond, Scleroseforeningen, and the Independent Research Fund Denmark.