Insights gained primarily from in vitro models of p53 regulators and effectors within our research program have led to a critical need for in vivo validation and the ability to gain further understanding using in vivo models. The phenotypes that are actively being examined in the p53 paradigm are no longer simply a matter of cell death, growth arrest or senescence. Instead, the role of p53 activation in vivo will likely have different consequences In different cell and tissue types and will likely differ with regard to developmental stages. The Cell and Animal Model Core (Core B) will derive and maintain human and mouse cell lines as well as adequate stocks of early passage aliquots of frozen primary cells utilized by the projects. It will serve as a repository for monoclonal antibodies and validated RNAi reagents. The Core will also acquire and maintain steadily used mouse models (transgenic, knockouts, etc.) and primary cells derived from these mice for distribution to the investigators in the Program. The research efforts of our productive and collaborative program greatly benefit from an in vivo models component, which maintains small breeding colonies of critically needed mouse strains for genetic and cell biologic investigations by our investigators. The high cost of animal studies in barrier facilities can be reduced substantially by the availability of shared technical support for mouse breeding and genetic analyses and for shared immunohistochemistry. The cost effectiveness is further emphasized by the shared use of the same genetically modified strains by several investigators and projects within the Program. Lastly, the core will provide expertise and guidance in the preparation of tissue and/or embryos for analyses of gene expression (protein and mRNA in situ).
The interactive and collaborative nature of the Program is enhanced by the resources provided by the Cell and Animal Model Core (Core B). This plays an essential role in facilitating the ongoing studies into pathways that are critical for the roles of p53 in tumor suppression, innate immunity and DNA damage responses.
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|Ou, Yang; Wang, Shang-Jui; Jiang, Le et al. (2015) p53 Protein-mediated regulation of phosphoglycerate dehydrogenase (PHGDH) is crucial for the apoptotic response upon serine starvation. J Biol Chem 290:457-66|
|Hiraki, Masatsugu; Hwang, So-Young; Cao, Shugeng et al. (2015) Small-Molecule Reactivation of Mutant p53 to Wild-Type-like p53 through the p53-Hsp40 Regulatory Axis. Chem Biol 22:1206-16|
|Resnick-Silverman, Lois; Manfredi, James J (2015) Two Faces of SIVA. Cancer Discov 5:581-3|
|Jiang, Le; Kon, Ning; Li, Tongyuan et al. (2015) Ferroptosis as a p53-mediated activity during tumour suppression. Nature 520:57-62|
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