The Cell and Tissue Imaging Core A is comprised of a centralized, cutting-edge microscopy facility, absolutely essential to the research goals of the 4 Projects in this PO1 application entitled "New therapies for liver fibrosis and hyperproliferation in alpha1-AT deficiency (ATD)". The facility is housed within the Center for Biologic Imaging (CBI) ( at the main campus of the University of Pittsburgh Medical Center. All Project Pis have made, and continue to make, heavy and diverse use of the CBI for facility-specific imaging methodologies. Evidence of the longevity of this use is seen in co-authored publications between the PI of Core A (Stolz), and/or other faculty and staff members at the Center for Biologic Imaging and Pi's ofthe individual projects. The imaging specialties afforded by CBI include all ultrastructural electron microscopy (transmission electron microscopy, scanning electron microscopy, immuno-electron SEM and TEM, negative staining), light and fluorescence microscopy (macro, dissecting, light and fluorescence, epi-fluorescence, confocal scanning and multi-photon imaging), live cell microscopy (transmitted light and fluorescence) and advanced fluorescence specialties like FRET;FRAP spectral analysis and ratiometric imaging. Also critical to data processing, a wide range of image analysis, quantitative evaluation software and technical assistance is available to program investigators and their laboratory staff. Since the expertise and equipment is located in one centralized facility, seamless integration among imaging modalities can be realized. Furthermore, instrumentation is accessible via programmable key card and is available 24/7 by trained users. Trained users can sign up for time through our on-line scheduling website which also serves as an internet-based data sharing venue among Pis.

Public Health Relevance

The Cell and Tissue) Imaging Core A is highly relevant to all the projects within this Program Project application. Each of the 4 projects requires a variety of imaging technologies to achieve the goals outlined in the specific aims. Pis of this program receive considerable access to expertise on design of imaging experiments, preparation of samples, and analysis of imaging data. Consequently, the CBI can serve as a clearinghouse of information and reagents that results in efficient sharing of data and resources among Pis.

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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O'Reilly, Linda P; Long, Olivia S; Cobanoglu, Murat C et al. (2014) A genome-wide RNAi screen identifies potential drug targets in a C. elegans model of ?1-antitrypsin deficiency. Hum Mol Genet 23:5123-32
Long, Olivia S; Benson, Joshua A; Kwak, Joon Hyeok et al. (2014) A C. elegans model of human ?1-antitrypsin deficiency links components of the RNAi pathway to misfolded protein turnover. Hum Mol Genet 23:5109-22
Miedel, Mark T; Zeng, Xuemei; Yates, Nathan A et al. (2014) Isolation of serpin-interacting proteins in C. elegans using protein affinity purification. Methods 68:536-41
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Chu, Andrew S; Perlmutter, David H; Wang, Yan (2014) Capitalizing on the autophagic response for treatment of liver disease caused by alpha-1-antitrypsin deficiency and other genetic diseases. Biomed Res Int 2014:459823
O'Reilly, Linda P; Perlmutter, David H; Silverman, Gary A et al. (2014) *1-antitrypsin deficiency and the hepatocytes - an elegans solution to drug discovery. Int J Biochem Cell Biol 47:109-12
Li, Jie; Pak, Stephen C; O'Reilly, Linda P et al. (2014) Fluphenazine reduces proteotoxicity in C. elegans and mammalian models of alpha-1-antitrypsin deficiency. PLoS One 9:e87260
Fox, Ira J; Daley, George Q; Goldman, Steven A et al. (2014) Stem cell therapy. Use of differentiated pluripotent stem cells as replacement therapy for treating disease. Science 345:1247391
Wang, Yan; Perlmutter, David H (2014) Targeting intracellular degradation pathways for treatment of liver disease caused by *1-antitrypsin deficiency. Pediatr Res 75:133-9

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