KSA-NIH and KUSCO are inviting two speakers, Dr. Ogyi Park (NIAAA, NIH) and Dr. Hwan Kyu
Lee (NHLBI, NIH), for the October session of KSA-KUSCO Seminar.
Time: October 8, 2009 (Thursday), 5:30 pm - 7:30 pm
Place: 9th Floor Conference Room (9S235) of Bldg. 10, NIH-Bethesda Campus
Title:
1. Dr. Ogyi Park (NIAAA, NIH), 5:30 pm
"Diverse roles of invariant natural killer T cells in liver injury and
fibrosis induced by carbon tetrachloride"
2. Dr. Hwan Kyu Lee (NHLBI, NIH), 6:30 pm
"Multiscale simulations of peptides, nanoparticles, and membranes for drug
delivery and nanopore applications"
Abstracts
1. Diverse roles of invariant natural killer T cells in liver injury and
fibrosis induced by carbon tetrachloride
Liver fibrosis is a common scarring response to all forms of chronic liver
injury and is always associated with inflammation that contributes to
fibrogenesis. Although a variety of cell populations infiltrate the liver
during inflammation, it is generically clear that CD8 T lymphocytes promote
while natural killer (NK) cells inhibit liver fibrosis.
However, the role of
invariant NKT (iNKT) cells, which are abundant in the liver, in hepatic
fibrogenesis, remains obscure. Here we show that iNKT-deficient mice are
more susceptible to carbon tetrachloride (CCl4)-induced acute liver injury
and inflammation. The protective effect of naturally activated iNKT in this
model is likely mediated via suppression of the proinflammatory effect of
activated hepatic stellate cells. Interestingly, strong activation of iNKT
through injection of iNKT activator {alpha}-galactosylceramide
({alpha}-GalCer) accelerates CCl4-induced acute liver injury and fibrosis.
In contrast, chronic CCl4 administration induces a similar degree of liver
injury in iNKT-deficient and wild-type mice, and only slightly higher grade
of liver fibrosis in iNKT-deficient mice than wild-type mice 2 weeks but not
4 weeks post CCl4injection although iNKT cells are able to kill activated
stallate cells. An insignificant role of iNKT in chronic liver injury and
fibrosis may be due to hepatic iNKT cell depletion. Finally, chronic
{alpha}-GalCer treatment had little effect on liver injury and fibrosis,
which is due to iNKT tolerance after {alpha}-GalCer injection. Conclusion:
natural activation of hepatic iNKT cells inhibits while strong activation of
iNKT cells by {alpha}-GalCer accelerates CCl4-induced acute liver injury,
inflammation, and fibrosis. During chronic liver injury, hepatic iNKT cells
are depleted and play a role in inhibiting liver fibrosis in the early stage
but not the late stage of fibrosis. (HEPATOLOGY 2008.)
2. Multiscale simulations of peptides, nanoparticles, and membranes for drug
delivery and nanopore applications
Interactions of peptides, nanoparticles, polymers, and membranes have been
studied using all-atom and coarse-grained molecular dynamics simulations.
The following topics will be presented:
(1) anchoring and tilting of the
lung-surfactant peptide interacting with monolayers;
(2) membrane curvature
and pore formation induced by differently sized, charged, shaped, and
concentrated nanoparticle (dendrimer) and linear polymer;
(3) conformation
and hydrodynamics of polyethylene glycol (PEG) in water and on surfaces;
(4)
self-assembly and phase behavior of PEG-conjugated vesicles, bicelles, and
micelles;
(5) parameterization of all-atom and coarse-grained models for
simulations described above. This work aids in the rational design of
synthetic peptides, nanoparticles, and drug complexes for drug delivery, and
development of accurate nanopores for biosensor applications.
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