The regulation of cellular behavior requires instructive cues from the local tissue environment. These cues include biochemical signals that act through activation of signaling and adhesion receptors. In addition, diverse mechanical cues are present in tissues, such as stiffness of the extracellular matrix and tissue tension, which are sensed by the cell and converted into a biochemical signal. Together, these cues trigger an intracellular response and ultimately decide on whether cells for instance proliferate, differentiate or migrate.
Uncontrolled cell division underlies the development of cancer. Most studies have focused on cell intrinsic mechanisms that control cell division and may be disrupted in cancer cells. Importantly, as local cues from the surrounding tissue instruct cells when to proliferate and eventually divide, loss of the underlying cell-cell communication will contribute to cancer development and progression as well. In addition, these cues provide spatial information that establishes the orientation of cell division, which determines the position of daughter cells in the tissue. Hereby, they may control tissue architecture and cell fate, and loss of correct division orientation has been linked to disruption of tissue organization and consequently tumor progression.
We are taking a reductionist approach to understand the contribution of individual extrinsic cues to the regulation of different aspects of cell division. We apply the gained molecular knowledge to different model systems, including intestinal organoids, to identify how these contribute to tissue development and homeostasis in health and disease.
Our current research revolves around the following questions:
- How do cues from the local tissue environment determine when cells divide?
- How do extracellular cues determine the orientation of cell division and how does this control tissue architecture and cell fate?
- How is tissue integrity maintained when cells go through mitosis?
Group members
- Willem-Jan Pannekoek - Post-doc, w.j.pannekoek@umcutrecht.nl
- Lisa Donker - PhD Student, l.donker@umcutrecht.nl
- Mirjam van der Net - PhD Student, m.c.vandernet-2@umcutrecht.nl
- Jooske Monster - PhD Student, j.l.monster@umcutrecht.nl
- Ronja Houtekamer - PhD Student, r.m.houtekamer@umcutrecht.nl
- Lars Kemp - PhD Student, l.j.s.kemp-2@umcutrecht.nl
- Marjolein Vliem - Technician, m.vliem@umcutrecht.nl
- Janneke Hummelink - Master student, j.a.hummelink@umcutrecht.nl
- Beau Neep - Master student, b.f.neep@umcutrecht.nl
- Anne Lankamp - Master student, a.a.lankamp-2@umcutrecht.nl