Congratulations to David C. Lyden, MD, PhD, Stavros S. Niarchos Professor in Pediatric Cardiology at Weill Cornell Medicine, who, together with Drs. Linnie Golightly, Associate Professor of Clinical Medicine, Shahin Rafii, Professor of Medicine and Raphael Lis, Assistant Professor of Reproductive Medicine in Medicine, received an R61 award titled, "In vitro modeling of brain blood barrier dysfunction on a chip to elucidate the pathogenesis of cerebral malaria."
Current limitations in understanding the pathogenesis of cerebral malaria stem from the lack of models that accurately reflect the human brain-blood barrier and how it is affected by malaria infection. Brain microvascular endothelial cells (BMECs) line the vascular network of the central nervous system along with the perivascular cells and form a specialized barrier called blood-brain barrier (BBB). The BBB regulates the traffic of select molecules in and out of the central nervous system, which can be altered if the BBB is disrupted. Studies of BBB dysfunction have been hampered by an inability to perform direct testing in patients and a lack of in vitro models. However, Drs. Rafii and Lis have developed a reprogramming strategy that allows them to develop durable and functionally true endothelial cells with BBB traits. The award will enable the application of this technology to the study of cerebral malaria. Specifically, the scientists developed a novel, state-of-the-art "chip" device that mimics the cell interface between the blood and the brain, and will reprogram circulating cells derived from children with or without cerebral malaria into BMECs to study their function. The chip will now help Drs. Lyden, Golightly and the team understand how malaria, a disease that kills and causes brain damage in children world-wide, communicates with the brain blood vessels through exosomes, particles surrounded by membranes that are involved in communication between cells. The team will analyze the contents of plasma exosomes isolated from Ghanaian children with cerebral malaria and evaluate their effect on the BBB endothelial cells in the "chip" to identify new ways to prevent or predict the brain damage caused by the parasite.
The award relies on ongoing collaborations with internationally recognized scientist and co-investigator, Dr. Ben Gyan, Associate Professor, Noguchi Memorial Institute for Medical Research, University of Ghana, for his expertise in malaria research and treatment, and will provide valuable resources for the wider community to pursue a multitude of studies that have not previously been possible due to the current limitations of existing humans model of human BBB dysfunction.