A remarkable feature of the vertebrate liver is its ability to regenerate following injury. Multiple parallel pathways feed into the regenerative response. We believe that unlocking the systems that control the regenerative response will lead to treatments for liver diseases. We are focusing upon the tumor necrosis factor (TNF) superfamily which is a large group of ligands and receptors with diverse biologic activities. Our laboratory is uncovering the exact intra- and extrahepatocellular events of the TNF related member, lymphotoxin. Specifically, we are examining the mechanisms by which this potent molecule contributes to liver regeneration. We are focusing upon the interactions between the lymphotoxin receptor on hepatocytes and lymphotoxin expressed on immune cells. First, we aim to show what cell survival mechanisms the lymphotoxin beta receptor triggers. Second, we link the production of interleukin 6 and stimulation of STAT3 phosphorylation to the lymphotoxin receptor. Third, we specifically tie the lymphotoxin receptor to the production of IL-6 and the intrahepatic cellular response. Together these aims will define the role of TNF superfamily member in liver regeneration and lead to a better understanding of what causes and could potentially prevent liver injury.

Public Health Relevance

Liver diseases are among the leading causes of death for Americans and few treatments options exist. Our laboratory seeks to understand how the liver responds to injuries. What we discover is relevant to livers diseases such as viral and non-viral hepatitis, chronic liver disease and liver cancer.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK080736-05
Application #
8609023
Study Section
Hepatobiliary Pathophysiology Study Section (HBPP)
Program Officer
Serrano, Jose
Project Start
2010-04-05
Project End
2015-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
5
Fiscal Year
2014
Total Cost
$332,090
Indirect Cost
$93,007
Name
Johns Hopkins University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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