Optimal brain functioning relies on the central nervous system (CNS) maintaining a meticulously regulated environment, free from toxins and pathogens. This is achieved through the coordination function of brain barriers; The specialized CNS vasculature referred to as the blood-brain barrier (BBB), and the blood-cerebrospinal fluid (CSF) barrier located in brain ventricles.  Similar to the BBB endothelium, the choroid plexus (CP) epithelium dictates the selectivity of the blood-CSF barrier (BCSFB). Immune cells continuously traverse our body, crossing vascular and epithelial barriers from the blood into various tissues for surveillance or to fight infection. However, the brain has long been considered an immune-privileged organ. Barriers protecting the brain against infection were also thought to block entry of immune cells. This dogma was recently overturned when it became clear that immune cells cross, mainly for surveillance, especially at the BCSFB. Harmful immune cell trafficking is a hallmark of brain autoimmunity such as in Neuro-Lupus and in Multiple sclerosis. Previous studies in our lab have investigated BCSFB dysfunction in Lupus and discovered a brain lymphoid structure with enhanced immune cell trafficking. Dominant transepithelial leukocyte migration enables us to catch the trafficking events ‘red-handed’ and to identify molecular and cellular trafficking mechanisms. Throughout Ron’s research, he will harness innovative methodologies involving single cell RNAseq, Super-Resolution microscopy, Imaging cytometry, and genetic/pharmacological interventions, aiming to decipher the fundamental question of how leukocytes enter the brain. He will classify specialized immune and epithelial barrier cell types, identify trafficking molecular pathways, and develop approaches to regulate the process.

Supervisor: Prof. Ayal Ben Zvi