The primary objective of the Pathology Core for this P01 is to facilitate the discovery and validation of novel targets and therapies for melanoma. To test the therapeutic efficacy of targeted therapies, it is essential to conduct well-planned research using state-of-the art preclinical models;these include patient-derived xenografts (PDXs), transgenic Tyr:creERT2, BRAF[CA/+], [ca/+], PTEN[lox/lox] melanoma mice, and syngeneic models using melanoma cell lines from the mice. As over 1000 patients with melanoma are seen and treated at University of Pennsylvania Health system per year, the Pathology Core is well equipped to provide fresh melanoma tissues to the Cell Biology Core to generate PDXs. Standardized procedures for procurement, processing, storage, quality control, histopathologic evaluation and distribution of samples will ensure optimal utilization and distribution of limited tissue samples to P01 projects. In addition to human samples, the pathology core will serve as a central repository for all mouse tissue generated by this P. The Pathology Core will provide technical support for developing and performing tissue-based assays and the core pathologist will provide expert pathological assistance in the interpretation of histological and immunostaining data. Centralized tissue repository, tissue processing, result acquisition and data interpretation will enable more collaboration across projects and allow new paths of research to emerge. The Core is led by a senior dermatopathologist with extensive experience in translational and laboratory investigation. The Pathology Core will interact with other P01 Cores and other core facilities at Penn and Wistar to support P01 projects. This coordination will allow the P01 investigators to most efficiently perform tissue-based research to find new therapeutic targets as well as to evaluate new combination therapies. In addition to tailoring services to the needs of each project, the central coordination and analysis of tissue will be time- and cost-effective.
Melanoma is the most aggressive form of skin cancer and the incidence of melanoma continues to rise worldwide. Current melanoma therapies are either ineffective or they elicit short-lived responses due to the rapid development of treatment resistance. The Pathology Core will allow the P01 investigators to most efficiently perform tissue-based research to find new therapeutic targets as well as to evaluate new combination therapies.
|Webster, Marie R; Xu, Mai; Kinzler, Kathryn A et al. (2015) Wnt5A promotes an adaptive, senescent-like stress response, while continuing to drive invasion in melanoma cells. Pigment Cell Melanoma Res 28:184-95|
|Leu, Julia I-Ju; Zhang, Pingfeng; Murphy, Maureen E et al. (2014) Structural basis for the inhibition of HSP70 and DnaK chaperones by small-molecule targeting of a C-terminal allosteric pocket. ACS Chem Biol 9:2508-16|
|Vultur, A; Villanueva, J; Krepler, C et al. (2014) MEK inhibition affects STAT3 signaling and invasion in human melanoma cell lines. Oncogene 33:1850-61|
|Streib, Manuel; Kraling, Katja; Richter, Kristin et al. (2014) An organometallic inhibitor for the human repair enzyme 7,8-dihydro-8-oxoguanosine triphosphatase. Angew Chem Int Ed Engl 53:305-9|
|Ma, Xiao-Hong; Piao, Sheng-Fu; Dey, Souvik et al. (2014) Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma. J Clin Invest 124:1406-17|
|Zhang, Pingfeng; Leu, Julia I-Ju; Murphy, Maureen E et al. (2014) Crystal structure of the stress-inducible human heat shock protein 70 substrate-binding domain in complex with peptide substrate. PLoS One 9:e103518|
|Wang, Tao; Ge, Yingbin; Xiao, Min et al. (2014) SECTM1 produced by tumor cells attracts human monocytes via CD7-mediated activation of the PI3K pathway. J Invest Dermatol 134:1108-18|
|Malecka, Kimberly A; Fera, Daniela; Schultz, David C et al. (2014) Identification and characterization of small molecule human papillomavirus E6 inhibitors. ACS Chem Biol 9:1603-12|
|Licciulli, Silvia; Maksimoska, Jasna; Zhou, Chun et al. (2013) FRAX597, a small molecule inhibitor of the p21-activated kinases, inhibits tumorigenesis of neurofibromatosis type 2 (NF2)-associated Schwannomas. J Biol Chem 288:29105-14|
|Kastl, Anja; Dieckmann, Sandra; Wahler, Kathrin et al. (2013) Rhenium complexes with visible-light-induced anticancer activity. ChemMedChem 8:924-7|
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