Protein Networks


Research Interests

High throughput proteomics, mass spectrometry, signal transduction, protein-protein interactions, tumorigenesis

Description of Research

The goal of the laboratory is to understand how protein complexes regulate cellular behavior. Inside the cell the majority of proteins can be found in highly interactive networks. The architecture of the cellular network and how it changes in response to the cellular environment is critical for the normal physiological functioning of the cell. In fact, these networks are responsible for the robustness and adaptability of living cells and perturbations to these networks result in pathological conditions such as cancer and neurological disorders. The response of the network to a stimulis is largely driven by the formation of new, transitory interactions, which are typically regulated by post translational modifications. Mass spectrometry is one of the most powerful techniques to uncover the architecture of these networks and how the network responds to perturbation. The laboratory uses high throughput mass spectrometry to gain insights into the protein interaction networks from a variety of normal and pathological conditions.

In particular, the studies in the laboratory have focused on the role of Ubiquitination in the response to DNA damage.  Importantly, DNA damage induces the formation of many new protein complexes and Ubiquitin functions as a scaffold, or bridge, to hold these complexes together.  As part of this work, the laboratory has uncovered a novel Ubiquitin binding domain, which functions only in DNA replication and repair. Furthermore, this Ubiquitin binding domain functions synergistically with other domains to direct the formation of Ubiquitin dependent complexes.

Example of a protein complex identified in a laboratory
Example of a protein complex identified in a laboratory

Recent Publications

Hoek, M., Myers, M.P., Stillman, B. 2011. An analysis of CAF-1-interacting proteins reveals dynamic and direct interactions with the KU complex and 14-3-3 proteins. J Biol Chem 286,  10876-10887 PubMed link

Kula, A., Guerra, J., Knezevich, A., Kleva, D., Myers, M.P., Marcello, A. 2011. Characterization of the HIV-1 RNA associated proteome identifies Matrin 3 as a nuclear cofactor of Rev function. Retrovirology 8, 60 PubMed link

Tomaic, V., Pim, D., Thomas, M., Massimi, P., Myers, M.P., Banks, L. 2011. Regulation of the human papillomavirus type 18 E6/E6AP ubiquitin ligase complex by the HECT domain-containing protein EDD. J Virol 85, 3120-3127 PubMed link

Sinha, R., Allemand, E., Zhang, Z., Karni, R., Myers, M.P., et al. 2010. Arginine Methylation Controls the Subcellular Localization and Functions of the Oncoprotein Splicing Factor SF2/ASF. Mol Cell Biol 30, 2762-2764 PubMed link

Bish, R.A., Fregoso, O.I., Piccini, A., Myers, M.P. 2008. Conjugation of complex polyubiquitin chains to WRNIP1. Journal of Proteome Research 7, 3481-3489 PubMed link

Bish, R.A., Myers, M.P. 2007. Werner helicase interacting protein 1 (WRNIP1) binds polyubiquitin via its zinc finger domain. J Biol Chem. 282, 23184-23193 PubMed link