School of Medicine
Cancer Cell Biology
Area of interest
Human cells have the ability to encode more than twenty thousand unique proteins. The protein landscape, or “proteome” (which proteins are expressed and the respective levels of each), is dynamically reorganized in response to environmental changes and stress, as cells grow and divide, and during cancer initiation and progression. The proteome is controlled by two distinct mechanisms: transcriptional regulation of gene expression and the targeted degradation of specific proteins. While there are robust methods that analyze global changes in transcription, limited tools are available to systematically assess global changes in protein degradation.
To address these challenges, we are developing and applying emerging genetic and proteomic techniques. GPS (Global Protein Stability Profiling) is a genetic screening platform that combines fluorescent activated cell sorting together with DNA microarray deconvolution to simultaneously interrogate the regulated stability of more than 15,000 proteins encoded by the Human ORFeome Collection. As a complementary strategy to GPS, we also utilize a proteomic approach termed QUAINT (Quantitative Ubiquitylation Interrogation). QUAINT is a mass spectrometry based platform that quantitatively measures changes in protein ubiquitylation for endogenous proteins. Together, these two technologies can provide a deep snapshot into the regulated cellular proteome.
Cancer is fundamentally a disease of cell cycle de-regulation, and we are therefore focused on systematically identifying the regulatory circuits controlling protein degradation throughout the cell cycle. In addition, since DNA damaging agents and mitotic inhibitors are the two most commonly used clinical anti-cancer agents, we are also focused on how these compounds affect proteome reorganization.
- Emanuele MJ, Elia EH, Xu Q, Thoma CR, Izhar L, Guo A, Rush J, Hsu PW, Yen HS, Elledge SJ. Global Identification of Modular Cullin-Ring Ligase Substrates. Cell. 2011 Oct 14;147(2):459-74.
- Emanuele MJ, Ciccia A, Elia AE, Elledge SJ. Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate. PNAS 2011. 108 (24) 9845-9850.
- Luo J, Emanuele MJ, Li D, Creighton CJ, Schlabach MR, Westbrook TF, Wong K, Elledge SJ. A genome-wide RNAi screen identifies multiple synthetic lethal interactions with the Ras oncogene.Cell. 2009 May 29; 137(5). 835-48.
- Emanuele MJ, Lan W, Jwa M, Miller SA, Chan, CSM, Stukenberg PT. Aurora B kinase and Protein Phosphatase 1 have opposing roles in modulating kinetochore assembly. J Cell Biol. 2008 Apr 21;181(2):241-54.
- Emanuele MJ and Stukenberg PT. Xenopus Cep57 is a novel kinetochore component involved in microtubule attachment. Cell. 2007 Sep 7;130(5):893-905.