Our overall goal is to understand the interconnected regulation of cell movement and proliferation in health and disease. We investigate cellular control systems by identifying key signaling components and measure when and where signaling occurs in normal, cancer and disease states. We use live-cell microscopy to watch cells signal as they move and proliferate. To understand cell signaling processes requires that we develop and apply new reporter and perturbation tools in combination with advanced automated live-cell fluorescent microscopes and analysis tools we have setup and develop in the lab. These live-cell approaches are closely integrated with automated multiplexed immunostaining and advanced analysis methods to comprehensively explore how mammalian regulatory systems are built. We integrate these approaches with systematic genomic and targeted screens, single-cell sequencing analysis, and quantitative models of signaling pathways. Current projects focus on how signals at the plasma membrane control movement, proliferation, quiescence and senescence using in vitro cell models and organoids, and we are validating key findings using mouse models.
Ongoing control of cell proliferation is needed to maintain tissue function throughout life. Regulation of both cell-cycle entry and exit is important as most adult mammals have subsets of stem, progenitor and differentiated cells that can switch between proliferation and quiescence. The goal of our work is to understand the underlying signaling system how normal mammalian cells as well as cancer cells control cell-cycle entry and exit decision processes by combining cultured cell models, organoids with cutting edge in vivo and in vitro single-cell analysis.
One of the open questions in the control of cell division and movement is the mechanism how cells sense contact with other cells and then transduce these signals to control cell-cycle entry and polarized migration. We are particularly excited about recent findings of the role of polarization of signaling activities that result from polarized distribution of cortical actin, membrane curvature, ER-plasma membrane junctions, receptors, actin bundling proteins and other structural and signaling components. In future work, we seek for example to answer the question how the same signaling pathways are often used to polarize cells and also to trigger proliferation. A key part of these projects are the use of micropatterned surfaces, the development of 2 and 3D models as well as in vivo studies using mammalian tissue sections to investigate cell movement and proliferation in an in vitro and more physiological context.