The central goal of Project 2 is to understand the role of alternative splicing in cancer. Cancer cells display extensive qualitative and quantitative dysregulation of splicing, and a subset of the isoforms that are inappropriately expressed can contribute to tumorigenesis. The mechanisms and pathways through which the splicing-factor oncoprotein SRSF1 and related members of the SR protein family transform cells will be investigated. Organotypic culture, as well as orthotopic and transgenic mouse models will be used to study transformation promoted by these splicing factors and their cooperation with other oncogenes in different cancer contexts. How these factors themselves are regulated in normal cells and upregulated in cancer will be addressed. High-throughput methods will be employed to systematically identify the splicing targets of SR proteins in human cells, and selected targets involved in tumorigenesis will be analyzed in detail. Splicing factors that contribute to the distinctive glycolytic metabolism of cancer cells will be identified and characterized, and alternative splicing of pyruvate kinase pre-mRNA will be investigated as a potential therapeutic target by specifically manipulating this process in tumors.
cells in ways that can contribute to tumor growth. By studying the role of alternative splicing in cancer, unique vulnerabilities of cancer cells may be uncovered that can be exploited therapeutically.
| Banito, Ana; Li, Xiang; Laporte, Aimée N et al. (2018) The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma. Cancer Cell 34:346-348 |
| Skucha, Anna; Ebner, Jessica; Schmöllerl, Johannes et al. (2018) MLL-fusion-driven leukemia requires SETD2 to safeguard genomic integrity. Nat Commun 9:1983 |
| Banito, Ana; Li, Xiang; Laporte, Aimée N et al. (2018) The SS18-SSX Oncoprotein Hijacks KDM2B-PRC1.1 to Drive Synovial Sarcoma. Cancer Cell 33:527-541.e8 |
| Lin, Kuan-Ting; Ma, Wai Kit; Scharner, Juergen et al. (2018) A human-specific switch of alternatively spliced AFMID isoforms contributes to TP53 mutations and tumor recurrence in hepatocellular carcinoma. Genome Res : |
| On, Kin Fan; Jaremko, Matt; Stillman, Bruce et al. (2018) A structural view of the initiators for chromosome replication. Curr Opin Struct Biol 53:131-139 |
| Knott, Simon R V; Wagenblast, Elvin; Khan, Showkhin et al. (2018) Asparagine bioavailability governs metastasis in a model of breast cancer. Nature 554:378-381 |
| Shamay, Yosi; Shah, Janki; I??k, Mehtap et al. (2018) Quantitative self-assembly prediction yields targeted nanomedicines. Nat Mater 17:361-368 |
| Tramentozzi, Elisa; Ferraro, Paola; Hossain, Manzar et al. (2018) The dNTP triphosphohydrolase activity of SAMHD1 persists during S-phase when the enzyme is phosphorylated at T592. Cell Cycle 17:1102-1114 |
| Arun, Gayatri; Diermeier, Sarah D; Spector, David L (2018) Therapeutic Targeting of Long Non-Coding RNAs in Cancer. Trends Mol Med 24:257-277 |
| Tarumoto, Yusuke; Lu, Bin; Somerville, Tim D D et al. (2018) LKB1, Salt-Inducible Kinases, and MEF2C Are Linked Dependencies in Acute Myeloid Leukemia. Mol Cell 69:1017-1027.e6 |
Showing the most recent 10 out of 610 publications
