Research
Our lab investigates molecular mechanisms that control dynamics in cell signaling. Currently, we are focusing on the function of internal motions in activation of ERK2, the role of the WRAMP protein network in rear-directed cell migration, and identification of signaling pathways underlying re-sensitization to drugs in melanoma. 聽All of our projects use the power of protein mass spectrometry to investigate changes in protein and cellular states.聽
The role of protein dynamics in controlling the allosteric activation of ERK2
This project tackles the challenging question of how intramolecular protein dynamics are coupled to regulation of catalysis in enzymes. The MAP kinases, ERK1 and ERK2, promote cell proliferation, survival, migration and invasion, and are emerging therapeutic targets for treating cancer. 聽We have discovered that dual phosphorylation and activation of ERK2 leads to changes in protein dynamics, resulting in global motions of the activated state. The motions can be modeled as a slow, reversible equilibrium be