Mahalia S. Desruisseaux, MD

The focus of the Desruisseaux laboratory is on the brain microvascular and neural cell responses to parasitic infections that lead to debilitating neurological sequelae and mortality, and on the mechanisms that underlie these responses.

The Desruisseaux laboratory works on cerebral malaria, a disease in which > 25% of survivors suffer from persistent neurological and cognitive deficits, despite successful anti-parasitic treatment. The goal of the laboratory is to identify the factors that cause these adverse long-term neurological sequelae.

The Desruisseaux lab has been particularly interested in the aberrant regulation of cerebral vascular tone, inflammation, blood-brain barrier disturbances, and eventually neuronal and glial degeneration after plasmodial infection, using a mouse model of experimental cerebral malaria. Our focus is on alterations in the synthesis and activation of vasomodulatory compounds during parasitic disease, and the effects of these alterations on cerebral perfusion, inflammation and blood-brain barrier disruption, and ultimately on gliopathy, neuronal damage and long-term neurological deficits. We identified endothelin-1, a potent vasoactive peptide with mitogenic and pro-inflammatory properties, as a key contributor to endothelial remodeling, neuroinflammation, long-term neurological damage and mortality during cerebral malaria. We also demonstrated that tau protein, a protein important in the formation of neurofibrillary tangles in neurodegenerative diseases, is abnormally regulated in our experimental model, demonstrating that long term sequelae are the result of potentially reversible vascular, biochemical and physiological changes in brains of infected mice.

In collaboration with investigators at the University of Malawi College of Medicine in Blantyre Malawi and at Indiana University, our laboratory will study the mechanisms of the disease process in pediatric patients from malaria endemic regions to test the translatability of our findings in the experimental model and to potentially derive novel therapeutic targets.