“We are interested in understanding how cell-cell communication within the stem cell microenvironment controls their biology in health and disease, with an emphasis on tissue repair and cancer.”
To remain functional, adult organisms rely on intrinsic regenerative processes that maintain both correct cell types and numbers in healthy tissue, and restore damaged tissue after injury. In most tissues both types of adult regeneration depend on the presence of somatic stem and progenitor cells that generate new cells. The local microenvironment which progenitor cells are exposed to is critical to regulating their behaviour. Most stem cells reside within specialised ‘niches’ that provide them with the spatial and temporal cues required to coordinate self-renewal and differentiation. We are interested in understanding how cell-cell communication within the stem cell microenvironment controls their biology in health and disease, with an emphasis on tissue repair and cancer.
We focus on two regenerative processes: peripheral nerve repair and adult neurogenesis in the subventricular zone of the brain. Our research approach combines cell biology, imaging, siRNA screens, deep sequencing and biochemistry techniques in primary co-cultures and in vivo models. By understanding the cellular and molecular mechanisms that regulate stem cell identity and function, we ultimately hope to identify novel therapeutic strategies for enhancing endogenous regeneration for the treatment of nervous system pathology.
Left: Dedifferentiated td-Tomato+ Schwann cells migrating collectively across the nerve wound to promote nerve regeneration. Right: GFAP+ Type-B SVZ neural stem cells (green) extending basal projections to blood vessels (red) and making contact at specialized endfeet (arrows).
Ottone C., Krusche B., Whitby A., Clements M., Quadrato G., Pitulescu M.E., Adams R.H. and Parrinello S. (2014). Direct cell-cell contact with the vascular niche maintains quiescent neural stem cells. Nature Cell Biology, doi:10.1038/ncb3045, published online
Parrinello, S., Napoli, I., Ribeiro, S., Digby, P. W. W., Fedorova, M., Parkinson, D. B., Doddrell, R. D., Nakayama, M., Adams, R. H., & Lloyd, A. C. (2010). EphB signaling directs peripheral nerve regeneration through sox2-dependent schwann cell sorting. Cell, 143(1), 145–155.
Parrinello, S., & Lloyd, A. C. (2009). Neurofibroma development in NF1–insights into tumour initiation. Trends in Cell Biology, 19(8), 395–403.
Parrinello, S., Noon, L. A., Harrisingh, M. C., Wingfield, P., Rosenberg, L. H., Cremona, C. A., Echave, P., Flanagan, A. M., Parada, L. F., & Lloyd, A. C. (2008). NF1 loss disrupts schwann cell-axonal interactions: a novel role for semaphorin 4F. Genes & Development, 22(23), 3335–3348.
Parrinello, S., Coppe, J.-P. P., Krtolica, A., & Campisi, J. (2005). Stromal-epithelial interactions in aging and cancer: senescent fibroblasts alter epithelial cell differentiation. Journal of Cell Science, 118(Pt 3), 485–496.
Parrinello, S., Samper, E., Krtolica, A., Goldstein, J., Melov, S., & Campisi, J. (2003). Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nature Cell Biology, 5(8), 741–747.