The focus of my research is the biology and pathobiology of the blood-brain barrier (BBB) and the role of the cerebral endothelium in inflammatory diseases of the central nervous system (CNS). The development of immune reactions in the CNS is different from other organs mainly due to the presence of the BBB that normally restricts the entry of leukocytes into the brain. A central question relates to the mechanisms by which immune cells gain access to the brain and spinal cord in infectious and inflammatory diseases. My laboratory has developed an in vitro model of the human blood-brain barrier (BBB) in which cerebral endothelial cells retain important morphological and functional characteristics of their in vivo counterparts. Over the last several years we have used this model reproducibly to study the molecular mechanisms that mediate and direct the traffic of inflammatory cells from blood into brain across the BBB in infectious, inflammatory, and autoimmune demyelinating diseases of the CNS and the factors responsible for the opening of the BBB in these disorders.
Specifically, we have addressed certain aspects of the BBB unique to human inflammatory CNS diseases:
Casiraghi C, Dorovini-Zis K, Horwitz MS. Epstein-Barr virus infection of human brain microvessel endothelial cells: A novel role in multiple sclerosis. J Neuroimmunol. 2011 Jan;230(1-2):173-7.
Chui R, Dorovini-Zis K. Regulation of CCL2 and CCL3 expression in human brain endothelial cells by cytokines and lipopolysaccharide. J Neuroinflammation. 2010 Jan 4;7:1.
Arjmandi A, Liu K, Dorovini-Zis K. Dendritic cell adhesion to cerebral endothelium: role of endothelial cell adhesion molecules and their ligands. J Neuropathol Exp Neurol. 2009 Mar;68(3):300-13.
Liu KK, Dorovini-Zis K. Regulation of CXCL12 and CXCR4 expression by human brain endothelial cells and their role in CD4+ and CD8+ T cell adhesion and transendothelial migration. J Neuroimmunol. 2009 Oct 30;215(1-2):49-64.
Yeung SN, Paton KE, Dorovini-Zis K, Chew JB, White VA. Histopathologic features of multiple myeloma involving the optic nerves. J Neuroophthalmol. 2008 Mar;28(1):12-6.
Wong D, Prameya R, Dorovini-Zis K. Adhesion and migration of polymorphonuclear leukocytes across human brain microvessel endothelial cells are differentially regulated by endothelial cell adhesion molecules and modulate monolayer permeability. J Neuroimmunol. 2007 Mar;184(1-2):136-48.