Acting 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
800 Commissioners Rd. East,
VRL, 6th Floor, Rm. A6-136
gcepinsk@uwo.ca or Gediminas.Cepinskas@lhsc.on.ca
Ph: (519) 685-8500, ext. 55077, 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 and dysfunction 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.
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, Western blots, EMSAs,
RT-PCR etc.)
