Róisín McManus studied natural science with a specialization in neuroscience for her undergraduate degree in Trinity College Dublin, Ireland, where she graduated with a first class honours (2010). Following this, she did a PhD under the joint supervision of Prof. Marina Lynch and Prof. Kingston Mills in Trinity College Dublin, Ireland, studying the effect of infection on the brain with age and in Alzheimer’s disease (2010-2015). Róisín worked as a post doc in the Lynch lab on biomarker development in dementia (2015), before joining Prof. Michael Heneka’s lab at the DZNE in Bonn, Germany (2015-2021). During her post doc with Prof. Heneka, Róisín investigated new roles for the NLRP3 inflammasome in contributing to Alzheimer’s disease, in addition to developing novel methods to inhibit NLRP3 inflammasome activation. Róisín joined Prof. Eicke Latz’s group at the DZNE and the III in 2021, where she was a senior postdoctoral researcher and an Alzheimer Forschung Initiative (AFI) project leader, overseeing a team of scientists together with Prof. Latz. In 2024 Róisín was awarded a Fellowship from the DZNE to establish her own research group. Her work examines how immune signalling influences microglial metabolic reprogramming, and looks to the role of metaflammation in driving neurodegenerative disease.
The focus of the McManus lab is to better understand how microglial metabolic changes and immune signalling converge to alter disease progression.
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.
