The Villen Lab seeks to develop and apply novel experimental and computational technologies for global proteome characterization to answer fundamental questions in cell biology and disease. We use quantitative mass spectrometry to measure dynamic changes in protein abundances, protein post-translational modification states, and to characterize interacting partners across multiple conditions.
We are particularly interested in studying protein phosphorylation as a general regulatory mechanism involved in a myriad of cellular functions. Two major questions we are trying to answer on a systems scale are: how phosphorylation is integrated into the multiple insults and responses to shape the proteome, and how signaling circuits evolved to accommodate proteome functional complexity. Some of the current projects in the lab in this area are:
- Characterization of protein phosphorylation events: Collecting massive data sets to unravel structural, functional and evolutionary features of phosphorylation.
- Oncogenic kinases and signaling pathways in breast cancer: Quantitative phosphoproteomics to understand signaling networks, and signatures in cancer onset.
- Signaling and aging: We are studying the signaling mechanisms underlying lifespan extension under dietary restriction, or via inhibition of mTOR.
We also aim to understand how protein concentrations are balanced, regulated and altered through gene expression and degradation to accomodate multiple cellular functions. Specifically, we are studying:
- Effects of protein phosphorylation in protein stability and degradation: Interplay of multiple postranslational modifications and effects in protein degradation.
- Protein translation as a mechanism to regulate protein concentration: Studying the mechanisms of protein translation and monitoring protein synthesis using quantitative mass spectrometry.