CORE C : Genomics Core (Two components: Affymetrix and Virus ) 1: Affymetrix microarray analysis of gene expression: Several components of this project will require analysis of gene expression in whole or micro-dissected liver tissue, from mouse and human samples. These studies will be performed in the genomics core for research of the department of Pathology. This core utilizes state of the art Affymetrix oligo-based cDNA microarrays (Mouse, human, C.Elegans, etc) for quantitative gene expression analysis. This facility is directed by Dr. Jian-Hua Luo, associate professor, department of pathology. Samples are provided as frozen tissue, on which, the facility performs RNA extraction and all other processing steps and provides the final data/results. This facility routinely processes human, mouse and rat samples and provides bio-informatic supportfor statistical analysis and data interpretation. 2: Virus core: Several components of this project will require genetic interventions readily supplied by Adeno-Associated Virus(AAV), recombinant adenovirus or Lentivirus. The virus core will collaborate with all investigators in this project for the design and preparation of suitable AAV or lentiviral based vectors to deliver transgenes and/or silencing RNA for overexpression or gene knock-down studies. This core will be directed by Dr. Aaron Bell, assistant professor, department of Pathology, who is highly experienced in AAV vector design. These approaches are well established in hepatic biology literature, and is already being used by Drs. Bell and Michalopoulos in collaborative research unrelated to this project which has validated its specificity and effectiveness. The AAV vectors allow for expression of transgenes up to 5KB and easily accommodates siRNA expression cassettes for gene knock-down studies.

Public Health Relevance

a-1-Antitrypsin deficiency is the most common cause of pediatric metabolic liver disease and can lead to cirrhosis and hepatocellular carcinoma in adults. Characterizing altered gene expression patterns and manipulation of gene expression with viral vectors currently used for clinical gene therapy applications is necessary to better understand the disease and may identify therapeutic targets and treatment modalities

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Program Projects (P01)
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Special Emphasis Panel (ZDK1-GRB-8)
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University of Pittsburgh
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