Meyer Lab Research

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.

Control of cell-cycle entry

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.

Relevant papers:

  • Pack L, Daigh LH, Meyer T. 2021. Nat Commun . 2021. Palbociclib induces selective and immediate dissociation of p21 from cyclin D-CDK4 to inhibit CDK2. Nature Communications 12(1):3356.
  • Yang HW, Cappell SD, Jaimovich A, Liu C, Chung M, Daigh LH, Pack LR, Fan Y, Regot S, Covert M, Meyer T. 2020. Stress-mediated exit to quiescence restricted by increasing persistence in CDK4/6 activation. Elife. 9:e44571.
  • Chung M, Liu C, Yang HW, Köberlin MS, Cappell SD, Meyer T. 2019. Transient Hysteresis in CDK4/6 Activity Underlies Passage of the Restriction Point in G1. Mol Cell. 76, 562-573.
  • Cappell SD, Mark KG, Garbett D, Pack LR, Rape M, Meyer T. 2018. EMI1 switches from being a substrate to an inhibitor of APC/CCDH1 to start the cell cycle. Nature. 558, 313-317.
  • Yang HW, Chung M, Kudo T, Meyer T. 2017. Competing memories of mitogen and p53 signalling control cell-cycle entry. Nature. 549, 404-408.
  • Cappell SD, Chung M, Jaimovich A, Spencer SL, Meyer T. 2016. Irreversible APC(Cdh1) Inactivation Underlies the Point of No Return for Cell-Cycle Entry. Cell. 166, 167-80.
  • Spencer SL, Cappell SD, Tsai FC, Overton KW, Wang CL, Meyer T. 2013. The Proliferation-Quiescence Decision Is Controlled by a Bifurcation in CDK2 Activity at Mitotic Exit. Cell. 155, 369-83.

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.

See the following publications for more about this work:

  • Bisaria A, Hayer A, Garbett D, Cohen D, Meyer T. 2020. Membrane proximal F-actin restricts local membrane protrusions and directs cell migration. Science Vol 368Issue 6496
  • Hayer A, Shao L, Chung M, Jouber LM, Yang HW, Tsai FC, Bisaria A, Betzig E, Meyer T. 2016. Engulfed cadherin fingers are polarized junctional structures between collectively migrating endothelial cells. Nat Cell Biol. 18, 1311-1323.
  • Yang HW, Collins SR, Meyer T. 2016. Locally excitable Cdc42 signals steer cells during chemotaxis. Nat Cell Biol. 18, 191-201.
  • Winans AM, Collins SR, Meyer T. 2016. Waves of actin and microtubule polymerization drive microtubule-based transport and neurite growth before single axon formation. Elife. 5, e12387.
  • Tsai FC, Seki A, Yang HW, Hayer A, Carrasco S, Malmersjö S, Meyer T. 2014. A polarized Ca2+, diacylglycerol and STIM1 signalling system regulates directed cell migration. Nat Cell Biol. 16, 133-44.