NORTHERN CALIFORNIA INSTITUTE FOR RESEARCH AND EDUCATION INC
Grant: $246,609 - National Institutes of Health - Sep. 30, 2009
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Award Description: This application for an NIH RC1 Challenge Grant in Health and Science Research addresses the following Challenge Areas: (04) Clinical Research and (15) Translation Science. The specific Challenge Topics it addresses are 04-DK-104, Improve the diagnosis, staging andt treatment of diseases of the liver; 15-CA-111, Infectious Disease and Inflammation in Cancer, and 04-DK-111, Pilot and feasibility clinical research studies in diabetes, obesity, and metabolic, endocrine, digestive, liver, renal and urological diseases. Hepatitis B virus (HBV) is a major cause of serious liver diseases, including chronic hepatitis, cirrhosis and hepatocellular carcinoma (HCC) throughout the world and the US, especially among minorities such as African Americans, Native Americans, and Asian Americans. HCC has a dismal prognosis unless detected early, but screening methods have low sensitivity and specificity and are expensive. Recent clinical data have pointed to an association between HCC and HBV mutants with deletions in the preS2 region of the surface gene. We hypothesize that preS2 mutant HBV genomes play a causal role in HBV-associated carcinogenesis, and hence the apperance of these mutants in patients can be used as a markerfor high risk of HCC. We will test this hypothesis, by confirming an association between preS2 mutants and advanced stages of hepatitis B with a cross-sectional study, and determining if the presence of these mutants can be used as a marker for increased risk of HCC development in patients with chronic hepatitis B in a case-control study. These studies, unlike previous ones, will provide direct evidence on the possible utility of preS2 mutants as a marker of HCC risk in chronic hepatitis B, as well as lead in the future to the identification of molecular targets for the prevention and/or therapy of HCC.
Project Description: Recent clinical data have pointed to an association between HCC and HBV mutants with deletions in the preS2 region of the surface gene. We hypothesize that preS2 mutant HBV genomes play a causal role in HBV-associated carcinogenesis, and hence the appearance of these mutants in patients can be used as a marker for high risk HCC. We will test the hypothesis, by confirming an association between preS2 mutants and advanced stages of hepatitis B wtih a cross-sectional study, and determining if the presence of these mutants can be used as a marker for increased risk of HCC development in patients with chronic heaptitis B in a case-control study. These studies, unlike previous ones, will be performed on samples from American patients. It is anticipated that these experiments will provide direct evidence on the possible utility of preS2 mutants as a marker of HCC risk in chronic hepatitis B, as well as lead in the future identification of molecular targets for the prevention and/or therapy of HCC.
Infrastructure Description: NA
Jobs Summary: NCIRE/UCSF (1) A new MS graduate from the Yen laboratory, Kristen Andreatta (4 calendar months effort) will be hired as a research associate to train the new BS level research assistant, to oversee the experiments, and to perform primary data analysis. In addition she will help in presenting data at lab meetings and writing up manuscripts. She will also maintain the Applied Biosystems 313xl Genetic Analyzer and order supplies. (2) A new Oberlin BS graduate, Johanna Weaver, (12 calendar months effort) will be hired as a research assistant to carry out the bulk of the experiments. Specifically, she will perform DNA extraction from sera, perform DNA amplification and restriction digestion, and analyze the products on the Applied Biosystems 3130xl Genetic Analyzer. She will also assist in general lab maintenance and cleaning. Huntington Memorial Research Institute (Subcontract) (3) A laboratory assistant, Josh Sun (1 calendar month effort), will be retained to aliquot the serum samples and sending them to San Francisco via overnight express in a manner consistent with biosafety rules and regulations. (Total jobs reported: 0)
Project Status: Not Started
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