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EMORY UNIVERSITY

The parent project entitled "The Role of Leptin in Liver Fibrogenesis" was competetively renewed on April 1, 2008 for four years. This application was funded via the R01 investigator-initiated mechanism for four years. The central hypothesis of the parent grant continues to be that adiponectin protects against leptin-induced fibrosis in vitro and in vivo by adenosine mono-phosphate activated kinase . Three aims were established to test this hypothesis in the parent grant, but since total funding of the award was reduced by more than twenty-five percent we have been unable to replace or purchase equipment that is central to the aims of the parent application which requires extensive isolation and culture of hepatic stellate cells from rodents; and, isolation of protein lysates from such cells to perform critical cell biology and biochemistry studies. This administrative supplement only requests purchase for five pieces of capital equipment which we cannot now afford to purchase. No change to personnel, salary support, or the scope of the aims of the parent grant have been made. The parentgrant is nearing completion of only year one of the competing renewal. Three of the requested pieces of equipment: liquid nitrogen storage tank, CO2 incubator, and Coulter counter will be directly used for the isolation and culture of rodent hepatic stellate cells. The bulk of the work in Aims 1 and 2 require these cells for in vitro signal transduction work. Likewise the fourth piece of capital equipment requested is a new gel documentation system with software to record the results of phospho-proteins demonstrated by either immunoblot or immunoprecipitation. At present the system available to us is overused, old, and frequently is not operational. Finally, the fifth piece of equipment, the request for an inverted microscope--will be used to complete analysis of liver tissue obtained from experiments underway in the third aim of the parent grant. Experiments planned with this microscope include immunohistochemical staining and FITC which can be recorded rapidly for peer-review and future competing renewal of the parent grant. RELEVANCE of PROPOSAL TO THE AMERICAN PEOPLE AND THE US ECONOMY: Cirrhosis is the 9th leading cause of death in the United States and the only definitive cure is liver transplantation. Liver transplantation is a costly treatment that often has to be performed twice on the same individual. Discovering potential therapies for liver fibrosis--the precursor to cirrhosis--is vital to the public health of our country and may produce medical benefits and cost-savings to the American People

Clarification of Codes