Director, CENTRE FOR CRITICAL ILLNESS RESEARCH
Gediminas Cepinskas, D.V.M., Ph.D.
Research Scientist/Assistant
Professor
Lawson Health Research
Institute
Critical Illness Research
Depts. Medical Biophysics/Physiology
Western University
800 Commissioners Rd. East,
VRL, 6th Floor, Rm. A6-136
London, Ontario, CANADA N6C 6B5
Gediminas.Cepinskas@lhsc.on.ca or gcepinsk@uwo.ca
Ph: (519) 685-8500, ext. 55073
Fax: (519) 685-8341
The cellular and molecular aspects of the systemic inflammatory response syndrome (SIRS) is the prime focus in my laboratory.
In general, SIRS is a prolonged generalized inflammation affecting multiple organs (such as lung, heart, liver and even brain) which are remotely localized from the initial inflammatory insult (such as physical trauma or bacterial infection). Clinically, SIRS/sepsis represents a major problem with extremely high mortality rate worldwide.
While SIRS-affected organs are structurally and functionally different, they are “united” by the blood vessel lining cells called vascular endothelial cells. In health, vascular endothelium provides a non-adhesive and anti-thrombotic surface for many blood-born components, including circulating immunocompetent cells, leukocytes (white blood cells). However, during SIRS, vascular endothelium becomes activated (displays pro-adhesive and pro-thrombotic phenotype) and plays a key role in facilitating the recruitment of leukocytes, a key marker of inflammation, to the affected organs. While leukocyte recruitment to the inflamed tissue(s) is part of the body’s natural defense against the initiating factors, an overwhelming accumulation of these cells results in a further damage of the affected organs. Therefore, understanding the cellular and molecular mechanisms of endothelial cell/leukocyte adhesive interaction and the underlying “cross-talk” between these two cell types, is a key step in order to successfully interfere with the magnitude of inflammation in SIRS-affected organs.
The current specific projects of my research are related to:
1) Molecular mechanisms of endothelial cell PECAM-1 (CD-31)-signaling induced by migrating polymorphonuclear leukocytes (PMN).
2) Modulation of endothelial cell pro-inflammatory phenotype and survival by migrating PMN.
3) Cerebrovascular endothelial cell dysfunction in sepsis: role of astrocytes.
4) Carbon monoxide (CO)-dependent modulation of inflammation.
Various aspects related to the above projects are addressed by employing both, in vivo and in vitro experimental approaches and various cell/molecular biology techniques, such as leukocyte-endothelial cell adhesion and leukocyte transendothelial migration assays, confocal microscopy etc.)
