Translational Neuroimmunology

Dr. Róisín McManus

Areas of investigation/research focus

Unlike peripheral organs, the brain and the cells within are very sensitive to inflammation, therefore any immune response must be tightly controlled. Microglia are highly phagocytic immune cells that express an array of pattern recognition receptors (PRRs) to detect pathogen- or danger-associated molecular patterns (PAMPs or DAMPs respectively) and quickly respond to threat or injury in the central nervous system (CNS). However, in aging or in neurodegenerative conditions like Alzheimer’s disease, microglial signalling becomes impaired. This affects neighbouring neurons and astrocytes, leading to chronic inflammation that ultimately causes disease acceleration. We have previously shown an important role for the microglial NLRP3 inflammasome in this process.

The focus of the McManus lab is to better understand how microglial metabolic changes and immune signalling converge to alter disease progression. Using a combination of preclinical models (transgenic animal models, primary cultures and human iPSCs) and clinical samples we perform an experimental and multi-omic approach to understand the following topics:

  1. Microglial innate immune response in the development of neurodegenerative disease
  2. Microglial immunometabolism in regulating cellular function
  3. The role of environmental factors like Western diet in driving neuroinflammation

There is currently no way to prevent the development of neurodegenerative diseases such as Alzheimer’s disease. The insights generated are crucial for the identification of novel immune-targeted therapies to provide better, patient-specific options for individuals with inflammatory or neurodegenerative conditions.

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