My research interests revolve around the host-pathogen interaction between bacterial pathogens and the human blood-brain barrier. Specifically how the blood-brain barrier fails to protect the brain during disease.
The human brain is an extremely demanding organ in the body. While only representing about 2% of the total body mass, it requires up to 20% of the total nutrients and oxygen. The primary role of the capillaries in the brain is to serve the brain’s needs by transporting beneficial substrates into the brain while restricting potentially harmful compounds and pathogens. Collectively the endothelial cells that comprise the lining of these brain capillaries are called the blood-brain barrier (BBB). The highly specialized brain endothelial cells (BECs) possess unique characteristics that greatly differ from blood vessels of peripheral tissues. These BECs cooperate in a number of ways to promote proper central nervous system homeostasis and brain function. However in many disease states the BBB is compromised leading to a number of complications and neuropathologies. Using human induced pluripotent (iPSC) stem cell technologies, we are able to derive BECs from iPSC sources that better mimic BBB phenotypes when compared to many other in vitro models. This allows us to interrogate the host-pathogen interaction with the BBB and examine barrier function and physiology during infection with meningeal pathogens.
Bacterial meningitis is a serious infection of the CNS that occurs when bacteria are able to gain access to the CNS by crossing or disrupting the BBB. When left untreated, bacterial meningitis is a uniformly fatal disease. Modern medical interventions have transformed bacterial meningitis into an often curable condition, however many survivors may still experience long lasting neurological problems such as deafness, blindness, seizures, and others. My research focuses primarily on the clinically relevant meningeal pathogens Streptococcus agalactiae (Group B Streptococcus, GBS), and Neisseria meningitidis (meningococcus, Nm) and how they are able to subvert the BBB’s defenses and gain access to the CNS.
