Academic Rank:
Professor
Affiliation(s):
VGH/VCHRI
Short Bio:
  • KATERINA DOROVINI-ZIS, MD, FRCPC, is Professor of Pathology and Laboratory Medicine at the University of British Columbia.Dr. Dorovini-Zis earned her M.D. degree form the National University of Athens, Greece. She completed a residency in anatomical pathology and neuropathology at Vancouver General Hospital. After a research fellowship at the National Institutes of Neurological Disorders and Stroke, NIH, supported by a Fogarty Fellowship (1977-1980), she joined the faculty of the University of Michigan in 1980. She joined the faculty of the University of British Columbia in 1985. Dr. Dorovini-Zis has held memberships with many organizations. She was the recipient of the Women in Neuroimmunology Award for her contributions to the field of Neuroimmunology, at the Vth International Congress of Neuroimmunology in 1998. She has authored and co-authored over 70 publications and several book chapters. She has served on grant review committees for the Multiple Sclerosis Society of Canada, the Canadian Heart and Stroke Foundation and the Alberta Health Foundation for Medical Research and as editorial board member in several journals. She has been actively involved in undergraduate, graduate and post-graduate teaching. She worked as Consultant Neuropathologist at Vancouver General Hospital and served as Head of the Division of Neuropathology from 1994 to 2007. She is the director of the Neuropathology Research Laboratory.Dr. Dorovini-Zis’ primary research interest is to understand the mechanisms of leukocyte recruitment across the blood-brain barrier in central nervous system inflammation, focusing on the role of the cerebral endothelium as an active participant in this process. Upon establishing her independent Neuropathology Research Laboratory in 1985, she created the first in vitro model of the human blood-brain barrier that mimics the blood-brain barrier in vivo. This model has been used in her laboratory to investigate the mechanisms that support adhesion and migration of different leukocyte subtypes (lymphocytes, monocytes, neutrophils, dendritic cells) across the blood-brain barrier and determine the effects of inflammatory mediators on barrier permeability and on how endothelial-derived adhesion molecules, class II MHC, costimulatory molecules and chemokines mediate leukocyte-endothelial cell interactions at the blood-brain barrier. Her interests extend to the study of blood-brain barrier dysfunction in infectious and inflammatory CNS diseases with particular emphasis on the mechanisms responsible for blood-brain barrier dysfunction and brain damage in pediatric cerebral malaria.

Academic background

  • National University of Athens MD. 1969
  • Residency in Anatomical Pathology (VGH) and Neuropathology (VGH and NIH)
  • Fogarty Fellowship, NINDS, N.I.H. 1977

Awards and Recognition

  • Teacher Investigator Award, NINDS, N.I.H. 1982-85
  • Women in Neuroimmunology Award. 1998
  • Honorable Mention-Weil Award for Best Paper in Experimental Neuropathology. 1998

Publications

  • Zis O, Zhang S, Dorovini-Zis K, Wang L, Song W. Hypoxia signaling regulates macrophage migration inhibitory factor (MIF) expression in stroke. Mol. Neurobiol. Epub 2014 May 15.
  • Liu KKY and Dorovini-Zis K. Differential regulation of CD4+T cell adhesion to cerebral microvascular endothelium by the b-chemokines CCL2 and CCL3. Int. J. Mol. Sci. 13:16119-16140, 2012..
  • 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. Epub 2010 Sep 9.
  • Dorovini-Zis K, Schmidt K, Huynh H, Fu W, Whitten RO, Milner D, Kamiza S, Molyneux M, Taylor TE. The Neuropathology of fatal cerebral malaria in Malawian children. Am. J. Pathology. In Press. 2011
  • 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.
  • 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. Epub 2009 Sep 18.
  • 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.
  • 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.
  • Yong RL, Kavanagh EC, Fenton D, Dorovini-Zis K, Heran MK, Haw CS. Midline cerebellar medulloblastoma in a seventy-one-year-old patient. Can J Neurol Sci. 2006 Feb;33(1):101-4.

Research Interest

  • Biology and pathobiology of the blood-brain barrier
  • Neuroinflammation
  • Neuroimmunology
  • My primary research interest is to understand the mechanisms of leukocyte recruitment across the blood-brain barrier in central nervous system inflammation, focusing on the role of the cerebral endothelium as an active participant in this process.  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.

Our in vitro and in vivo studies have addressed certain aspects of the BBB unique to human inflammatory CNS diseases:

  • Expression of endothelial cell adhesion molecules and their functional significance in the adhesion and migration of lymphocytes, monocytes, dendritic cells and polymorphonuclear leukocytes across the endothelium.
  • Expression and function of class II MHC and co-stimulatory molecules in costimulation and antigen presentation.
  • Expression of chemokines and their role in the adhesion and directional movement of T lymphocyte subsets, monocytes and dendritic cells across the cerebral endothelium.
  • Modulation of the permeability of the BBB by cytokines, nitric oxide and during leukocyte transmigration.
  • Mechanisms responsible for blood-brain barrier dysfunction and brain damage in pediatric cerebral malaria.
  • Participation of dendritic cells and T regulatory cells in neuroinflammation.