Research
Microglia are the brain’s resident immune cells
Understanding Microglial States
Originally considered a homogenous cell type, recent work has revealed that microglia can adopt discrete, co-existing transcriptional 'states', both in mouse and humans. Advances in single-cell and spatial transcriptomics have provided a glimpse into this diversity, revealing that microglia adopt distinct gene expression programs in different contexts such as development, injury and aging. However, the dynamics, formation and, critically, the functions of these microglial states remain poorly understood, representing a poorly explored frontier of neuroscience.
Our goal is to address these fundamental questions and leverage these insights to precisely modulate neuroinflammation during aging and neurodegeneration. We aim to define the principles that govern microglial plasticity. Understanding microglial states at a mechanistic level will not only provide fundamental insights into brain immunity but also lay the foundation for therapeutic interventions targeting microglia in neurodegenerative and neuroinflammatory diseases.
Our lab combines in vitro and in vivo models with cutting-edge single cell and spatial genomics technologies to address the following questions:
How are microglial states formed?
We investigate the molecular mechanisms that drive microglial state transitions, focusing on intercellular signaling pathways, transcription factors and epigenetic regulation.
What are the functions of different microglial states?
We dissect if and how microglial states subserve distinct neurobiological functions. We examine how these microglial subtypes interact with other brain cells, in addition to the immune periphery in neurodegeneration and repair.
Can we develop better tools to study and manipulate microglia?
To overcome technical challenges of studying microglia, we develop new molecular and genomic tools to monitor and manipulate their function with high precision. This includes novel genomic technologies that integrate multiomic measurements and next-generation viral vectors to genetically access microglia and their subtypes.
Microglia, the resident immune cells of the central nervous system (CNS), are key regulators of brain function and dysfunction. Human genetic studies have placed microglia at the center of neurodegenerative and neuroinflammatory diseases, including Alzheimer’s disease (AD) and multiple sclerosis (MS). Moreover, microglia activation is a hallmark of numerous neuropathologies, including epilepsy and traumatic brain injury. Microglia also have critical beneficial functions, playing an essential role in brain repair, in particular the regeneration of white matter, which degenerates in disease and aging. Yet, how microglia contribute to brain function, pathology and repair remains poorly understood.