The goal of this Core is to provide the analytical tools and statistical and computational expertise needed to design and analyze the high throughput experiments and data generated by the Projects and Cores of this POI. Additionally, this Core will integrate the data resulting from the Project with external cancer genome data such as that generated by The Cancer Genome Atlas (TCGA) project, in order to elucidate the mechanism(s) of drug resistance.
The Specific Aims of Core 3 are (1) to perform genomic characterization of human and mouse cancer genomes and integrating these data to identify events that cause resistance;(2) Analyze the shRNA and drug response data to identify dependencies in pre-treatment and relapsed cells;(3) Integrate data from this P01 with comprehensive genomic data generated by The Cancer Genome Atlas (TCGA) project to increase statistical power. At the end of the funded period, integrative analysis of all data produced within this P01 and external data will yield a clear set of hypotheses regarding candidate genes, pathways and drugs that are involved in and can affect the development of drug resistance in BRAF-mutant melanoma.
|Eliades, Philip; Abraham, Brian J; Ji, Zhenyu et al. (2018) High MITF Expression Is Associated with Super-Enhancers and Suppressed by CDK7 Inhibition in Melanoma. J Invest Dermatol 138:1582-1590|
|Nguyen, Nhu T; Fisher, David E (2018) MITF and UV responses in skin: From pigmentation to addiction. Pigment Cell Melanoma Res :|
|Kapp, Friedrich G; Perlin, Julie R; Hagedorn, Elliott J et al. (2018) Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche. Nature 558:445-448|
|Romano, Gabriele; Chen, Pei-Ling; Song, Ping et al. (2018) A Preexisting Rare PIK3CAE545K Subpopulation Confers Clinical Resistance to MEK plus CDK4/6 Inhibition in NRAS Melanoma and Is Dependent on S6K1 Signaling. Cancer Discov 8:556-567|
|Wein, Marc N; Foretz, Marc; Fisher, David E et al. (2018) Salt-Inducible Kinases: Physiology, Regulation by cAMP, and Therapeutic Potential. Trends Endocrinol Metab 29:723-735|
|Levy, Carmit; Golan, Tamar; Fisher, David E (2018) miRNA-211 stops the clock. Noncoding RNA Investig 2:|
|Byrne, Elizabeth H; Fisher, David E (2017) Immune and molecular correlates in melanoma treated with immune checkpoint blockade. Cancer 123:2143-2153|
|Lin, William M; Fisher, David E (2017) Signaling and Immune Regulation in Melanoma Development and Responses to Therapy. Annu Rev Pathol 12:75-102|
|Kawakami, Akinori; Fisher, David E (2017) The master role of microphthalmia-associated transcription factor in melanocyte and melanoma biology. Lab Invest 97:649-656|
|Reuben, Alexandre; Spencer, Christine N; Prieto, Peter A et al. (2017) Genomic and immune heterogeneity are associated with differential responses to therapy in melanoma. NPJ Genom Med 2:|
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