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Cirrhosis Research Program
Cirrhosis Research Program
The Cirrhosis Research Center's mission is to stimulate basic and
translational research on developments of new therapeutic and
preventive modalities of cirrhosis; and to serve the Southern
California community by disseminating research information on
cirrhosis.
Components
Non-Parenchymal Liver Cell Core Laboratory
This laboratory funded by NIAAA, provides three types of non-parenchymal liver cells to investigators to support
their cutting-edge cellular and molecular research on cirrhosis. This
service is available to both our Center members and non-members (on a chargeback
basis). Please go to our
Cores page for more information.
Animal Models for Cirrhosis
The Animal Core Laboratory provides different models of liver fibrosis
and cirrhosis to assist investigators. Please go to our
Cores page for more information.
Pilot Project Funding
The Center funds pilot projects to support new investigators.
Please
go to our
Pilot Projects page for more information.
Ongoing Research
Molecular
Understanding of Liver Fibrosis
Liver fibrosis is the excessive formation of fibrous scar tissue that
replaces normal liver tissue and disrupts liver functions when it
progresses to cirrhosis. To design new and innovative therapies for
cirrhosis, it is essential to understand molecular mechanisms responsible
for “activation” of hepatic stellate cells that
leads to excessive production of fibrous materials. Dr. Yuan-Ping Han’s
research discloses that a combination of the pro-inflammatory mediator
IL-1 and a type of fibrous materials called collagen,
stimulates the initial activation of hepatic stellate
cells via release of enzymes called MMP-9. Blocking the activity of MMP-9
prevents the cell activation. Dr. Tsukamoto’s laboratory tests a unique
proposal that hepatic stellate cells are like
fat cells and molecular regulation required for precursor cells to become
fat cells, is indeed needed to prevent hepatic stellate
cell activation or to reverse activated stellate
cells to normal and quiescent cells. In fact, his research identifies
certain proteins that controls fat cell specific
genes as potential molecular targets for reversal of stellate
cell activation and anti-cirrhosis modalities.
Cirrhosis and Liver Cancer
Cirrhosis markedly increases the risk of developing liver cancer and
genetic and environmental factors play pivotal roles in the genesis of
both diseases. Among such environmental factors, diabetes, alcohol
drinking, certain nutrients and viral infection are shown to be
important. Dr. Keigo Machida
investigates alcohol or high fat diet promotes the incidence of liver
injury and cancer in mouse models that are genetically manipulated to
produce proteins of hepatitis C virus. The findings from his studies are
shading crucial insights into the understanding of the interactions between
environmental factors and hepatitis viruses and into formulation of new
preventive strategies.
Iron and Liver Inflammation, Cirrhosis and Cancer
Iron is an essential nutrient but is readily accumulated in liver during
chronic inflammation. Research conducted by Dr. Hide Tsukamoto’s team
shows that accumulated iron, in turn worsens liver inflammation and
fibrosis via a novel signaling mechanism recently disclosed by them.
Further, their research demonstrates iron stimulates survival and
proliferation of liver cancer cells. Based on these findings, a new
therapeutic approach is being tested to suppress liver inflammation,
fibrosis, and growth of liver tumor via selective reduction of iron.
Gene Therapy of Cirrhosis
Based on new findings generated from molecular research described above,
gene therapies are being tested for liver fibrosis in animal models.
Examples include introducing the genes that facilitates a reversal of
activated hepatic stellate cells to quiescent
cells (PPARy or that block signaling of factors implicated in
activation of the cells (WntMMPs).
Liver Development and Regeneration
Dr. Kasper Wang of the Los Angeles Children’s Hospital has discovered a
growth factor called fibroblast
grow factor 10 (FGF-10) is released by hepatic stellate
cells to promote development of the liver in mouse embryo. FGF-10 is also
shown to be important in regeneration (new growth) of the adult mouse
liver which is known to be impaired in different types of chronic liver
disease including alcoholic liver disease. New information gained from
his study will help develop novel approaches to promote liver growth and
healing.
Dr. Kinji Asahina was recently recruited to the Center from the
Tokyo Medical and Dental University where he performed similar
work on mouse embryonic stem
cells. He will develop a new research program of developmental biology
specifically focused on the identification of the origin on hepatic stellate
cells and the precise roles of hepatic stellate
cells in liver development.
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Attend A Free Community Seminar
"Health Effects of Alchohol:
What Your Patients Need to Know"
| Date: |
TBA |
| Place: |
Rancho Los Angeles National Rehabilitation Center
7601 E. Imperial Hwy.
Downey, CA 90242 |
3rd Annual International Symposium
July 17 and 18, 2008
Bilbao, Spain
This two-day International Symposium will be hosted by José Mato, CIC BioGUNE, and José Fernández-Checa, University of Barcelona.
Alcohol and Your Health
Online Education Click Here
Support the Center
Learn how to support our research... More
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