The Department of Biology's newest faculty member, Associate Professor Sandra Rieger, explores wound repair using the zebra fish as a model system
How sensory nerve endings in the skin interact with skin cells, such as epidermal keratinocytes, is a fundamentally understudied research area. This knowledge is however highly important as these interactions promote wound repair and limb regeneration, and their perturbations are known to lead to disease conditions like peripheral neuropathy. The Rieger lab is working on several questions with regard to axon-keratinocyte interactions:
1. What type of interactions exist between somatosensory neurons and epidermal keratinocytes?
2. What molecular processes promote the crosstalk between both cell types?
3. How are these molecular processes perturbed under disease conditions?
4. Can we manipulate molecular pathways in neurons or keratinocytes to develop treatments for degenerative conditions leading to peripheral sensory neuropathy, and to wound healing deficits?
We focus on mechanisms involving hydrogen peroxide (H2O2), as we identified this molecule to be a key mediator of the crosstalk between sensory neurons and keratinocytes following injury. We discovered that H2O2 generated in wound keratinocytes promotes sensory axon regeneration (Rieger & Sagasti, PLoS Biology 2011). We also found evidence that hormetic concentrations of H2O2 are critical for proper wound repair. If the concentrations are too high, H2O2 can damage keratinocytes and induce wound healing defects. Similarly, we identified that high concentrations of H2O2 are induced in keratinocytes during treatment with the chemotherapeutic agent paclitaxel, leading to upregulation of the matrix-degrading metalloproteinase, MMP-13, in keratinocytes. Increased MMP-13 activity correlates with epidermal damage and sensory axon degeneration (Lisse et al., PNAS 2016).
We are using mainly zebrafish as a model system to characterize sensory neuron-keratinocyte interactions in vivo, and rodents for comparative purposes. We have completed several studies to characterize the role of H2O2 in wound repair and are currently identifying H2O2-dependent molecular processes leading to sensory axon regeneration. We have also established zebrafish in vivo models with which to study the crosstalk between sensory neurons and keratinocytes under conditions of paclitaxel and glucose (diabetes) treatment.
Another project relates to the question how sensory nerve endings interact with wound epidermis following limb amputation. We are particularly interested in the role of Anterior Gradient Protein in this process, which has been shown to function in a nerve-dependent manner during newt limb regeneration. We are currently exploring the role of one family member of the Anterior Gradient Protein family in this process
