The PDAC Antibody Core will produce novel monoclonal antibodies that are directed against known or suspected protein targets expressed in human and mouse pancreatic ductal adenocarcinoma (PDAC), pancreatic intraepithelial neoplasia (PanIN) as well as in the surrounding stromal tissues. The Core will work closely with program investigators to identify suitable protein targets, generate the appropriate antigens, develop the appropriate immunization strategies and implement the screening procedures necessary to identify the most useful monoclonal antibodies. The PDAC Antibody Core will provide a centralized resource for information related to the specificity and applications of each antibody used by the program investigators. A significant aspect of the Core will be expert guidance in experimental design, antibody use and data analysis in studies utilizing both polyclonal and monoclonal antibodies. Monoclonal antibodies have the distinct advantage of reproducible reactivity that does not change with repeated antibody preparation. This feature is critical to the long-term goals of this program that are to provide antibody-based diagnostics, biomarkers and therapeutics with ultimate application in the clinic. Every project in this program has a significant requirement for antibodies to study signal transduction pathways and to identify, study and neutralize unique and novel cell surface targets in PDAC. The program's focus on both mouse models of PDAC and primary human PDAC tissue and cell lines will require antibodies that recognize the orthologous proteins and epitopes in both species. In addition, antibodies will be used to identify targets in a variety of applications including immunohistochemistry of formalin-fixed as well as fresh-frozen tissues, laser scanning cytometry, western blot, and flow cytometry. The PDAC Antibody Core will focus exclusively on the generation of antibodies that can serve these needs of the program's scientists. The PDAC Antibody Core will coordinate all monoclonal antibody production with the Dana-Farber/Harvard Cancer Center Monoclonal Antibody Core (DF/HCC-MAC). The DF/HCCMAC will be responsible for purchase and housing of animals, performing standard immunizations, and hybridoma fusions. Program investigators will be assessed a chargeback fee for this work in accordance with the fee schedule in place for DF/HCC investigators.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA117969-05
Application #
8015373
Study Section
Subcommittee G - Education (NCI)
Project Start
Project End
Budget Start
2010-01-01
Budget End
2010-12-31
Support Year
5
Fiscal Year
2010
Total Cost
$39,432
Indirect Cost
Name
Dana-Farber Cancer Institute
Department
Type
DUNS #
076580745
City
Boston
State
MA
Country
United States
Zip Code
02215
Patra, Krushna C; Kato, Yasutaka; Mizukami, Yusuke et al. (2018) Mutant GNAS drives pancreatic tumourigenesis by inducing PKA-mediated SIK suppression and reprogramming lipid metabolism. Nat Cell Biol 20:811-822
Anglin, Justin; Zavareh, Reza Beheshti; Sander, Philipp N et al. (2018) Discovery and optimization of aspartate aminotransferase 1 inhibitors to target redox balance in pancreatic ductal adenocarcinoma. Bioorg Med Chem Lett 28:2675-2678
Yang, Annan; Herter-Sprie, Grit; Zhang, Haikuo et al. (2018) Autophagy Sustains Pancreatic Cancer Growth through Both Cell-Autonomous and Nonautonomous Mechanisms. Cancer Discov 8:276-287
Santana-Codina, Naiara; Roeth, Anjali A; Zhang, Yi et al. (2018) Oncogenic KRAS supports pancreatic cancer through regulation of nucleotide synthesis. Nat Commun 9:4945
Lundquist, Mark R; Goncalves, Marcus D; Loughran, Ryan M et al. (2018) Phosphatidylinositol-5-Phosphate 4-Kinases Regulate Cellular Lipid Metabolism By Facilitating Autophagy. Mol Cell 70:531-544.e9
Hopkins, Benjamin D; Pauli, Chantal; Du, Xing et al. (2018) Suppression of insulin feedback enhances the efficacy of PI3K inhibitors. Nature 560:499-503
Biancur, Douglas E; Kimmelman, Alec C (2018) The plasticity of pancreatic cancer metabolism in tumor progression and therapeutic resistance. Biochim Biophys Acta Rev Cancer 1870:67-75
Chen, Yang; LeBleu, Valerie S; Carstens, Julienne L et al. (2018) Dual reporter genetic mouse models of pancreatic cancer identify an epithelial-to-mesenchymal transition-independent metastasis program. EMBO Mol Med 10:
Hill, Margaret A; Alexander, William B; Guo, Bing et al. (2018) Kras and Tp53 Mutations Cause Cholangiocyte- and Hepatocyte-Derived Cholangiocarcinoma. Cancer Res 78:4445-4451
Mendt, Mayela; Kamerkar, Sushrut; Sugimoto, Hikaru et al. (2018) Generation and testing of clinical-grade exosomes for pancreatic cancer. JCI Insight 3:

Showing the most recent 10 out of 134 publications