Research in the Meyer and Teruel Labs: Our overall goal is to understand the interconnected regulation of cell movement, proliferation and differentiation in health and disease. We investigate such cellular control systems by identifying key signaling components and measure when and where signaling occurs in normal, cancer and other disease states. We use live-cell microscopy to watch cells signal as they move, enter the cell cycle or differentiate. To understand these cell signaling processes requires that we develop and apply new reporter and perturbation tools in combination with advanced automated live-cell fluorescent microscopes we have setup in the lab. These live-cell approaches are closely integrated with automated multiplexed immunostaining, and machine learning, which allows us to comprehensively explore how mammalian regulatory systems are build. We further integrate these approaches with systematic genomic and targeted screens, single-cell RNAseq analysis, and quantitative models of signaling pathways. Specific projects typically focus on in vitro models or organoids, with the ultimate goal to understand processes such as adipogenesis (differentiation of fat cells), neurogenesis or intestinal differentiation which often requires that we validate 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.
We do not yet understand how hormonal oscillations, the circadian clock and the cell cycle coordinate cell differentiation processes for tissue development and maintenance. We are developing in vitro 2D and 3D models that can be used together with automated microscopy to track thousands of individual cells as their signals oscillate and they chose trajectories towards one or more differentiated states. Current model systems in the lab include adipogenesis and neurogenesis and focus for example on the questions how cells integrate different signals to balance the number of differentiated cells while maintaining pools of progenitor cells, and how cells select which of two differentiation trajectories to take.
A main research focus in the lab is on adipogenesis (fat cell differentiation) since defects in this process leads to obesity, diabetes, cardiovascular disease, and many types of cancer. A main issue in obesity and metabolic disease is faulty cell differentiation and dedifferentiation with adipocytes changing their differentiation program to become unresponsive to insulin. We are focusing on the idea that preventing the dedifferentiation of mature adipocytes and generating new healthy adipocytes improves metabolic health. Thus, the question we are asking is how one can control the number of newly differentiated cells and how one can maintain differentiated cells in a healthy state and prevent their dedifferentiation. We are using both in vitro models and in vivo validation in mice to understand how one can increase the number of differentiated cells and also lock differentiated adipocytes in a healthy state.