Epithelia need to respond to acute physiological stress, such as loss of barrier integrity upon wounding, the presence of aberrant cells arising from mutagenic processes or an increase in mechanical tension arising from organ growth. Failure to detect and respond to these challenges results in chronic stress, for example when aberrant cells continue to proliferate in the tissue and drive tumorigenesis. We use Drosophila as a model system to elucidate the mechanisms that detect and repair disruption of tissue homeostasis.
Signaling, regeneration and cancer
We use in vivo wounding, regeneration and cancer models to investigate why wound environments and cancer are characterized by the similar stress-responsive signaling signature, which prominently features JNK/AP-1, JAK/STAT and Hippo/YAP(TAZ) pathways. We want to understand how cross talk between these pathways balances injury-induced apoptosis, cell survival and regenerative proliferation to successfully restore tissue homeostasis after injury. We furthermore analyze changes to transcription and chromatin states, which promote epigenetic adaptation to tissue stress. To this end we established cell-type specific genome profiling by adapting DamID methods for our in vivo models.
Recognition and elimination of aberrant cells
We previously reported that the presence of aberrant cells characterised by erroneous fate specification induces enrichment of actomyosin at the cellular interface shared with wild type cells. We demonstrated that interface contractility is necessary to eliminate aberrantly specified cells from the tissue but that it is also sufficient to drive morphogenetic behaviors, such as cyst formation. We now address how aberrant cells are recognized by the surrounding wild type epithelium, how recognition may drive contractile changes at the interface between aberrant and wild type cells and how aberrant cells are efficiently eliminated from the epithelium by interface contractility.
Mechanics of 3D cell shape transitions
While epithelial cell adhesion, polarity and cytoskeleton dynamics are widely investigated, little is known about the mechanisms underlying epithelial morphogenesis along the squamous-cuboidal-columnar cell shape spectrum. We are building on our expertise to combine quantitative imaging, genetics and mathematical modelling to elucidate how the follicle epithelium enveloping the growing egg chamber transitions through different cell shapes. Our studies aim to understand the cell-autonomous and non-autonomous determinants of these fundamental cell shapes that are specific to protective, absorptive or secretory functions of epithelia.