MAT, Johns Hopkins School of Education, 2013
PhD, Leiden State University, 1990
MSc, Utrecht State University, 1985
My research interests focus on the role that the blood vessels in the brain play in modulating neurological function under different stress conditions, including microbial exposure such as Plasmodium. I am specifically interested in the pathogenesis of cerebral malaria (CM) and its neurologic sequelae. Since 2004 my laboratory has been in studying the activation of the blood brain barrier (BBB) and its relation to CM. My research efforts focus on the responses of the BBB endothelial cells to Plasmodium falciparum infected erythrocytes (PRBC) (Tripathi et al publications). I find this particularly interesting as most neurotropic pathogens first invade the central nervous system before conveying neuro-dysfunction, however, PRBC don’t do this and remain INSIDE the vasculature while causing seizures and coma. Upon clearance of infection patients are often left with neurologic sequelae, such as cognitive and psychological problems, seizures and attention deficit hyperactivity disorders.
The unique lining of the blood vessels in the brain -the BBB endothelium- differs from other endothelia (such as fenestrated liver endothelium), as it possesses tight junctions that form a strong barrier and play a crucial role in protecting the brain’s homeostatic environment to allow for normal neuronal function. The position of the BBB-endothelium in between events occurring in the periphery (sequestration of PRBC) and inside the brain (neurological dysfunction), makes the BBB the target of my investigations. We have shown that the BBB-endothelium is not a passive surface only guiding blood through the brain, but an interactive "relay station", communicating between the blood and brain compartment.
The Plasmodium parasite prevents clearance by the immune system and spleen by hiding out inside red blood cells and sequestering intravascular in high endothelial venules by using Plasmodium-encoded adhesive proteins on the red blood cell surface. Clinical symptoms of the sequestered Plasmodium infected red blood cells (PRBC) include coma and seizures. Upon clearance of infection neurological sequelae persist. It is unclear as to how the intravascular parasite does this. My research is focused on the interface of binding of PRBC to the brain vasculature and the events occurring inside the CNS. I am studying the activation of the blood brain barrier endothelium by PRBC and the effects on the underlying brain cells.
I found that PRBC activation of the brain endothelium involves both soluble and adhesive factors and results in a highly inflammatory state of the brain endothelium. The release of cytokines and chemokines to both sides of the brain endothelium leads at the blood side to a recruitment of immune cells and on the brain side to an activation of astrocytes and neuronal damage. We are now focusing on the specific inflammatory factors involved and how to ameliorate the brain activation and improve clinical outcome.
- Tripathi AK, Sha W, Shulaev V, Stins MF, Sullivan DJ Jr. Plasmodium falciparum infected erythrocytes induce NF-?B regulated inflammatory pathways in human cerebral endothelium. Blood. 5;114:4243-52 2009
- Abhai K Tripathi, David J Sullivan and Monique F Stins. Plasmodium falciparum Infected Erythrocytes decreases Blood Brain Barrier function / integrity. J.Infect Dis, 195, 2007,
- Tripathi AK, Sullivan DJ, Stins MF. Plasmodium falciparum-infected erythrocytes increase intercellular adhesion molecule 1 expression on brain endothelium through NF-kappaB. I&I. 74:3262-70, 2006
- Dennis J. Grab, Srabasti J. Chakravorty, Henri van der Heyde and Monique F. Stins. How can microbial interactions with the blood brain barrier modulate astroglial and neuronal function? Cell Microbiol. 2011 Oct;13(10):1470-8.
- Midrelle E. Noumbissi, Bianca Galasso and Monique F. Stins. Brain vascular heterogeneity: implications for disease pathogenesis and design of in vitro blood–brain barrier models.
Fluids and Barriers of the CNS201815:12
See all publications by Monique F. Stins