The overall objective of the Histology and Tissue Core is to serve as a central resource for collecting, preserving, annotating and distributing tissues, and provide high quality services and experimental support to all the projects. Given the inherent difficulties in obtaining large quantities of tissues from PC patients, we have devised and instituted a Rapid Autopsy Program that is designed to harvest primary tumor and organs containing all metastatic deposits of tumor from individuals who die of PC. The process we have instituted allows us to harvest and rapidly freeze these tissues within 2-3 hours of death. This process is unique and highly innovative as a tissue resource in that it allows us to capture the entire history disease progression for PC patients (from intact primary tumor and remaining precursor lesions through to distant metastases at all locations). In principle, we can reconstruct the entire organ from the freezer, which enables spatial distribution of multiple lesions and affected areas. To date, UNMC has performed overall 113 pancreas cancer autopsies and 2 non-cancer autopsies for a total of 115 autopsies as part of this effort. All rapid autopsy samples have been (and future samples will be) evaluated for quality using number of procedures (Northern blot, Southern blot, RNA-seq, PCR, SDS-PAGE, immunohistochemistry, in situ hybridization, immunofluorescence and other analyses with known probes) as part of the function of the core. For the purposes of this application, the resource will provide pathology support and high quality frozen samples, slides for frozen sections, formalin fixed tissues, and associated body fluids (blood, serum and ascites) for all projects requiring tissues. The histology core will also be responsible for the collection, processing and analysis of tumor tissues from animal models. The core will process, archive, and cut tissue section and assist in the standardization of staining protocols. The core has expertise in the analysis of malignant and benign pancreatic lesion including IPMNs, PanINs and PDAC and will be responsible to determine the impact of gene alterations and/or therapeutic interventions, on tumor tissue architecture (therapeutic response) and on non-target organs (Toxicology). In collaboration with the Animal Model and Experimental Therapeutics Core (AMETC), the histology core will be involved in the archiving and cataloguing of the specimens (tumor tissue, blood and other organs and body fluids) from patients and animal models. This core is a centralized fully equipped laboratory for the tissue collection, processing, histology, and immunohistochemistry work. It will be useful for all proposed projects and aims. The resource and service of this core will be available for University of Nebraska Medical Center personnel, as well as outside institutions working in pancreatic cancer. This service will bring much collaboration, integration and sharing reagents among the pancreatic cancer researchers involved in this program project and other projects under the umbrella of UNMC Pancreatic Cancer Research Program.
Pancreatic cancer is a highly aggressive malignancy and the underlying mechanisms of metastasis are poorly understood; hence the overall goal of this program project application is to comprehensively define the role of MUC16 mediated signaling and metabolomics alterations in promoting pancreatic cancer metastasis via three highly integrated research projects and cores. These efforts require high quality biospecimens and state-of the-art approaches to evaluate the histopathological impact of MUC16 on human and murine tissues. The Histology and Tissue Core will serve as a valuable resource to fulfill the requirements of the individual projects to provide high quality biospecimens and histology services.
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| Aithal, Abhijit; Rauth, Sanchita; Kshirsagar, Prakash et al. (2018) MUC16 as a novel target for cancer therapy. Expert Opin Ther Targets 22:675-686 |
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| Barkeer, Srikanth; Chugh, Seema; Batra, Surinder K et al. (2018) Glycosylation of Cancer Stem Cells: Function in Stemness, Tumorigenesis, and Metastasis. Neoplasia 20:813-825 |
| Barkeer, Srikanth; Chugh, Seema; Karmakar, Saswati et al. (2018) Novel role of O-glycosyltransferases GALNT3 and B3GNT3 in the self-renewal of pancreatic cancer stem cells. BMC Cancer 18:1157 |
| Chugh, Seema; Barkeer, Srikanth; Rachagani, Satyanarayana et al. (2018) Disruption of C1galt1 Gene Promotes Development and Metastasis of Pancreatic Adenocarcinomas in Mice. Gastroenterology 155:1608-1624 |
