Director, CENTRE FOR CRITICAL ILLNESS RESEARCH
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.
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.)
