The Role of Lymphotoxin Receptor in Liver Regeneration

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DESCRIPTION (provided by applicant): Candidate: I plan to pursue a career performing fundamental research in an academically strong Pathology Department. My long term goal is to understand the basic mechanisms of diseases affecting the liver and to apply that knowledge to combat human chronic liver diseases. My current plan is to uncover which LT beta receptor ligands are essential for liver regeneration and which lymphocyte subsets are involved in delivering the LT beta receptor ligands to the liver parenchyma. I am very eager and committed to continuing this project. The Mentored Clinical Scientist Development Award is critical to continue my progress towards becoming an independent physician scientist. This award will allow me to develop and expand my project as well as gain more specific and mentored training in the field of immunology. Environment: I am interested in liver pathology and the University of Chicago has an active liver transplantation program which provides a wealth of experience in interpreting liver biopsies. Dr. Yang-Xin Fu, the mentor, has extensive experience in cytokine research, the lymphotoxin system and training scientists to become independent basic research investigators. Research project: The tumor necrosis alpha (TNF-alpha) superfamily is a large group of ligands and receptors with diverse biologic activities. TNF-alpha signaling through the TNF receptor 1 is a proximal event in liver regeneration. However, the contribution of TNF-alpha related family member to liver regeneration has not been explored. The contribution of the lymphotoxin ligand and receptors system to liver regeneration is largely unknown. Our preliminary data suggests that signaling through lymphotoxin is involved in liver regeneration. We propose that delivery of lymphocyte derived lymphotoxin to the liver following partial hepatectomy is necessary for recovery of hepatic mass.