Mitogen-activated protein kinases (MAPKs) are universal elements of signaling pathways. ERK2 has long served as a prototype to define properties of MAPKs and their cascades. ERK2 and/or the closely related protein kinase ERK1 are required not only for embryogenesis, differentiation, and proliferation, but also for the everyday functions of differentiated cells, e.g., changes in membrane permeability, long term potentiation, and cell type-specific transcription.
The misregulated or otherwise inappropriate functions of ERK1/2 contribute to diseases ranging from cardio-facio-cutaneous syndrome to diabetes to cancer. We study how ERK1/2, essential, ubiquitous signaling proteins, act with ligand-dependent specificity. We are particularly interested in mechanisms of chromatin and DNA interactions and chromatin-bound functions, regulation of microtubule depolymerizing kinesins, control of pancreatic beta cell function, and how ERK1/2 are inactivated with specificity.
Small Cell Lung Cancer (SCLC)
An important goal is to understand how ERK1/2 contribute to tumor growth in cancer. The functions of ERK1/2 are often usurped in cancers, such as non-small cell lung cancer (NSCLC), to support proliferation, migration, and survival of tumors. On the other hand, ERK1/2 are inactivated in small cell lung cancer (SCLC), a neuroendocrine cancer, as they have been shown to inhibit SCLC survival. We are exploring these and other SCLC survival mechanisms that might be targeted therapeutically.