Projects per year
Anastasia obtained her B.Sc. (Hons) degree in Pharmacology from the University of Sunderland with a Sandwich year (in respiratory pharmacology) at Bayer PLC in 1998. Her PhD in cell biology and cell physiology took place at the University of East Anglia (2002) in the laboratory of Jelena Gavrilovic, and investigated the role of growth factor and cell-matrix interactions in alveolar epithelial wound healing.
Anastasia’s research career has been focussed in the biomedical area. Her postdoctoral positions (2002-2009) were undertaken in the Department of Respiratory Medicine at the University of Cambridge in the laboratories of Edwin Chilvers and Nicholas Morrell, where she investigated the role of granulocytes in lung inflammation and asthma, and receptor trafficking in pulmonary arterial hypertension.
In 2009 she worked at the Institute of Food Research, Norwich within the field of gut mucosal immunology. Here she aimed to understand how gut epithelial stem cells are regulated by the innate immune system during homeostasis and inflammatory bowel disease.
In October 2016 Anastasia joined the School of Pharmacy at the University of East Anglia as a Lecturer in Pharmacology.
Key Research Interests and Expertise
The long-standing research interest of this lab is the study of mucosal tissue, in particular that of the lung and the gut during health and inflammation. Experimentally we use an integrated approach; our research traverses epithelial stem cells, the innate immune system and commensal bacteria.
The key to a healthy mucosa is the maintenance of the epithelial barrier, which takes place by the division of epithelial stem cells, their differentiation into different epithelial cell types and the renewal of the epithelium. During homeostasis the epithelium forms a tight barrier preventing direct contact of the external environment i.e. microbes with underlying immune cells so preventing an inflammatory response.
Our research (Skoczek et al. 2014) has shown that immune cells underlying the epithelium are critical regulators of homeostasis in the gut. Using gut organotypic culture we have shown that in health the intact crypt epithelial barrier first detects any changes in bacterial composition of the gut lumen and then rapidly recruits underlying Ly6C+ monocytes (via the MyD88 signalling pathway) from the smooth muscle and submucosal layers to the crypt epithelial stem cell niche. This physical repositioning of monocytes is significant because it causes temporary alterations in the rate renewal of the epithelium thus allowing fine tuning of immune responses to maintain health and barrier function. We have also shown that monocytes help maintain the number of crypt epithelial stem cells in vivo; further supporting our hypothesis that immune-epithelial interactions are important in the maintenance of tissue homeostasis.
During inflammation the epithelial barrier is compromised, which allows bacteria to interact directly with the body’s immune system and an inflammatory response occurs. Our hypothesis is that the highly regulated homeostatic interaction between monocytes and epithelial stem cells we observed is dysregulated during inflammation.
Homeostasis is a tightly regulated process requiring finely-tuned complex interactions between different cell types, growth factors / cytokines and their receptors. Another hypothesis in my lab is that the signaling pathways of these factors also play a role in stem cell driven tissue renewal during homeostasis or inflammation and that these factors may be epithelial-derived (autocrine) or immune cell-derived (paracrine).
Recent work published also in the Journal of Immunology has demonstrated a previously unidentified role for autocrine IL-6 signaling in the maintenance of the small intestinal crypt stem cell niche, through the differential expression of the IL-6 receptor and downstream STAT3 signaling in Paneth cells and the Wnt signaling pathway.
PAST GROUP MEMBERS
Dagmara Skczoek (former PhD student)
Petr Walcyzsko (Postdoc)
Andy Goldson (Postdoc)
CURRENT GROUP MEMBERS
Vicki Jeffery (current PhD student)
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Lettice, F., Alexander, M., Askounis, A., Baker, A., Cammidge, A., Chao, Y., Fabian, L., Fielden, J., Hernaez Saenz De Zaitigui, M., Hui, O., Kaplani, E., Khimyak, Y., Liss, P., Lord, R., Marin, M. J., Mayes, A., Melendi-Espina, S., Nolte, S., Romanov, A., Saeed, A., Sobolewski, A., Tolhurst, T. & Wright, J.
6/11/20 → 5/05/22
29/07/19 → 6/09/19
Raveenthiraraj, S., Sobolewski, A., Palmitessa, V., Lippolis, A., Mastronardi, M., Armentano, R., Serino, G., De Angelis, M. & Chieppa, M., Apr 2020, In : Inflammatory Bowel Diseases. 26, 4, p. 546–556 11 p.
Research output: Contribution to journal › ArticleOpen AccessFile11 Citations (Scopus)27 Downloads (Pure)
Raveenthiraraj, S., Mastronardi, M., Santino, A., Serino, G., Lippolis, A., Sobolewski, A., Falconi, M. & Chieppa, M., 16 Nov 2019, In : International Journal of Molecular Sciences. 20, 22, 5771.
Research output: Contribution to journal › ArticleOpen AccessFile14 Citations (Scopus)20 Downloads (Pure)
A Bronze-Tomato Enriched Diet Affects the Intestinal Microbiome under Homeostatic and Inflammatory ConditionsLiso, M., De Santis, S., Scarano, A., Verna, G., Dicarlo, M., Galleggiante, V., Campiglia, P., Mastronardi, M., Lippolis, A., Vacca, M., Sobolewski, A., Serino, G., Butelli, E., De Angelis, M., Martin, C., Santino, A. & Chieppa, M., 2 Dec 2018, In : Nutrients. 10, 12, 1862.
Research output: Contribution to journal › ArticleOpen AccessFile15 Citations (Scopus)11 Downloads (Pure)
Jeffery, V., Goldson, A. J., Dainty, J. R., Chieppa, M. & Sobolewski, A., 1 Jul 2017, In : Journal of Immunology. 199, 1, p. 304-311 8 p.
Research output: Contribution to journal › Article42 Citations (Scopus)
Secretory Leukoprotease Inhibitor (Slpi) Expression Is Required for Educating Murine Dendritic Cells Inflammatory Response Following Quercetin ExposureDe Santis, S., Galleggiante, V., Scandiffio, L., Liso, M., Sommella, E., Sobolewski, A., Spilotro, V., Pinto, A., Campiglia, P., Serino, G., Santino, A., Notarnicola, M. & Chieppa, M., 6 Jul 2017, In : Nutrients. 9, 7, 706.
Research output: Contribution to journal › ArticleOpen AccessFile14 Citations (Scopus)14 Downloads (Pure)