Selasi Dankwa

Biological Sciences in Public Health, Harvard University, 2015

Endothelial cells that line the inner walls of blood vessels play a crucial role in maintaining blood vessel and organ function, and systemic health. Consequently, dysfunction of the endothelial barrier can have dire consequences in wide-ranging diseases like diabetes, sepsis and cerebral malaria.

In cerebral malaria, red blood cells infected with Plasmodium falciparum parasites accumulate in brain microvessels. This leads to endothelial activation and ultimately, dysfunction, characterized by disruption of the blood-brain barrier, clotting dysregulation, and brain swelling. The molecular underpinnings of brain pathology in cerebral malaria are not well understood, nor are there drugs that can reverse deadly brain swelling. 

• Our research aims to deepen our understanding of the molecular mechanisms that drive brain endothelial dysfunction and repair in cerebral malaria. We seek to:
• Investigate how endothelial cells respond to P. falciparum and other inflammatory stimuli;
• Define endothelial barrier-disruptive and barrier-restorative signaling pathways;
• Investigate the crosstalk between brain endothelial cells and perivascular cells that either potentiate barrier dysfunction or promote barrier function;
• Identify candidate barrier-strengthening therapeutics.

The knowledge gained from these studies will provide valuable insights into the complex regulation of endothelial barrier integrity in healthy and disease settings, leading to interventions that reduce complications and mortality associated with cerebral malaria and other vascular pathologies.