Cells respond to external stimuli by activating nonlinear and highly interconnected networks of signaling proteins. Our laboratory focuses on understanding how these networks are wired in different cell types and how they influence response to growth factors or cytotoxic agents using both hypothesis driven and systems-based data-driven approaches. Our lab combines approaches from molecular genetics with cell and systems biology to study a recently discovered Wnt5-Fzd2 signaling pathway in metastasis as well as cell-to-cell contact in regulating cell fate decisions.
1. Noncanonical Wnt5-Fzd2 signaling pathway. Metastasis is responsible for as much as 90% of cancer-associated mortality. Yet progress in developing effective drugs that specifically target metastasis or cells with metastatic potential has remained slow. Based on our recent discovery of a new noncanonical Frizzled 2 (Fzd2) pathway that drives epithelial-mesenchymal transition (EMT) and plays a key role in metastasis in a wide array of clinically challenging human tumors, a major focus of our lab is to advance the mechanistic understanding of how Fzd2 regulates cell motility and EMT and to determine how this pathway works in other cell types and processes, such as maintenance of tumor initiating cells or regulation of cell differentiation. To this end, approaches including multiplex proteomics, mouse genetics coupled with phenotypic measurements will be used to determine how proteins in this pathway interact with each other and how signals are augmented or attenuated through positive and negative feedback.
2. Fundamental Properties of the Cell Regulated by Cell-to-Cell Interaction. Cell-to-cell interactions control both body and organ size in metazoans. Though cell-to-cell contact has been a major focus of cell biology since the early days of cell culture (1950s-1970s), how cell-to-cell contact causes cell cycle arrest, stimulates differentiation, controls cell size and cell morphology, as well as regulates energy consumption remains poorly understood. The answers to these questions are not only important to a fundamental understanding of cell communication but also have unappreciated relevance in diseases such as cancer, inflammation, aging, metabolic and neurological disorders. Another focus of our lab is to pursue some of these less studied questions in cell biology by integrating recently developed proteomics and computational methods with specific cellular system.