A large repertoire of cellular proteins is subject to SUMO PTM. SUMOylation affects the conjugated protein's function, subcellular localization, and/or stability. Consistently, maintaining SUMO dynamics is important for normal cell physiology.

The onset of disease including cancer can alter the transcription, translation, and/or PTM of select components of the SUMO machinery. Naturally this disturbs the balance of SUMO modified to unmodified substrates. An imbalance in the kinetics of SUMO PTM can initiate cancer development; for example, induction of SENP1 (SP1) elicits cancerous transformation of the normal mouse prostate gland (Bawa-Khalfe et. al. 2007). Recently, we reported alternative splicing of the SENP7 (SP7) gene product that is readily observed in human metastatic breast cancer samples (Bawa-Khalfe et. al. 2012). However, it is unclear how the loss of SUMO equilibrium supports the cancer transcriptome and an aggressive metastatic phenotype in breast cancer.

We are currently applying multiple genomic, epigenetic, and proteomic techniques to address this question; these techniques include chromatin immunoprecipitation (ChIP), ChIP-Seq, RNA-Seq, RNA immunoprecipitation (RIP), mass spectrometry, and in-vitro PTM analysis. The studies are performed at the level of the chromatin, monolayer cell cultures, 3D-acini tumor models, and genetically engineered whole animal models. Hence, the laboratory's research integrates results from a single cancer cell and more complex heterogeneous tumor microenvironments. This multipronged approach will provide a more accurate assessment of the therapeutic and/or diagnostic potential of SUMO and other PTM systems in aggressive cancers.