Maarja Andaloussi Mäe – Mechanistic studies on the blood-brain barrier

Our research aims to understand the cellular and molecular mechanisms that regulate the blood-brain barrier (BBB) and to gain insights into BBB permeability.

The BBB refers to the unique characteristics of the mammalian brain endothelium that collectively protect the brain. The BBB consists of several distinct features:

  1. it restricts passive leakage of blood-borne proteins and pathogens into the brain through tight cell junctions and low transcytosis rates,
  2. it actively facilitates nutrient delivery via numerous influx solute carrier
  3. it protects against neurotoxic substances with a range of ATP-binding cassette efflux transporters.

BBB integrity is essential for healthy neuronal signaling in a normal brain. However, this barrier also presents challenges for delivering drugs and bioactive molecules to treat brain diseases.

Links between BBB and brain conditions

Evidence increasingly links BBB disruption to various cerebrovascular conditions (e.g., stroke), multifactorial aging diseases (e.g., Alzheimer’s), and rare monogenic brain disorders (e.g., cerebral cavernous malformations, CCM). Although BBB impairment is implicated in these disorders, the underlying molecular and cellular mechanisms remain poorly understood.

Mapping characteristics of the brain vasculature

To investigate BBB permeability under physiological conditions, we use a combination of mouse genetics, single-cell RNA sequencing, proteomics, fluorescent tracers, and immunofluorescent labeling techniques. Our goal is to systematically map molecular and cellular similarities and differences in the brain vasculature across various mouse models with BBB leakage.

Comparing transcriptomic and proteomic data from these models provides a unique opportunity to examine how different types of BBB disruption may lead to both common and distinct effects on non-endothelial cells (e.g., mural cells such as pericytes and smooth muscle cells, microglia, astrocytes) as well as on the endothelium itself.

Group members

Research leader: Maarja Andaloussi Mäe
Group members: Weihan Li, Elisa Vazquez

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