Sobolewski, Anastasia - University of East Anglia

个人简介

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 set-up a research group (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.

研究领域

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).

近期论文

查看导师最新文章（温馨提示：请注意重名现象，建议点开原文通过作者单位确认）

Reynolds, A., Wharton, N., Parris, A., Mitchell, E., Sobolewski, A., Kam, C., Bigwood, L., El Hadi, A., Münsterberg, A., Lewis, M., Speakman, C., Stebbings, W., Wharton, R., Sargen, K., Tighe, R., Jamieson, C., Hernon, J., Kapur, S., Oue, N., Yasui, W., Williams, M., Aged, 80 and over, Microscopy, Confocal(2014)Canonical Wnt signals combined with suppressed TGFβ/BMP pathways promote renewal of the native human colonic epitheliumin Gut63.pp. 610-621 Full Text UEA Repository(Article) Skoczek, D. A., Walczysko, P., Horn, N., Parris, A., Clare, S., Williams, M., Sobolewski, A.(2014)Luminal Microbes Promote Monocyte-Stem Cell Interactions Across a Healthy Colonic Epitheliumin Journal of Immunology193.pp. 439-451 Full Text UEA Repository(Article) Howard, L. S., Crosby, A., Vaughan, P., Sobolewski, A., Southwood, M., Foster, M. L., Chilvers, E. R., Morrell, N. W.(2012)Distinct responses to hypoxia in subpopulations of distal pulmonary artery cells contribute to pulmonary vascular remodeling in emphysemain Pulmonary Circulation2.pp. 241-249 Full Text UEA Repository(Article) Farahi, N., Uller, L., Juss, J. K., Langton, A. J., Cowburn, A. S., Gibson, A., Foster, M. R., Farrow, S. N., Marco-Casanova, P., Sobolewski, A., Condliffe, A. M., Chilvers, E. R.(2011)Effects of the cyclin-dependent kinase inhibitor R-roscovitine on eosinophil survival and clearancein Clinical & Experimental Allergy41.pp. 673-687 Full Text UEA Repository(Article) Sobolewski, A., Rudarakanchana, N., Upton, P. D., Yang, J., Crilley, T. K., Trembath, R. C., Morrell, N. W.(2008)Failure of bone morphogenetic protein receptor trafficking in pulmonary arterial hypertension: potential for rescuein Human Molecular Genetics17.pp. 3180-3190 Full Text UEA Repository(Article) Yang, J., Davies, R. J., Southwood, M., Long, L., Yang, X., Sobolewski, A., Upton, P. D., Trembath, R. C., Morrell, N. W.(2008)Mutations in Bone Morphogenetic Protein Type II Receptor Cause Dysregulation of Id Gene Expression in Pulmonary Artery Smooth Muscle Cells: Implications for Familial Pulmonary Arterial Hypertensionin Circulation Research102.pp. 1212-1221 Full Text UEA Repository(Article) Farahi, N., Cowburn, A. S., Upton, P. D., Deighton, J., Sobolewski, A., Gherardi, E., Morrell, N. W., Chilvers, E. R.(2007)Eotaxin-1/CC Chemokine Ligand 11: A Novel Eosinophil Survival Factor Secreted by Human Pulmonary Artery Endothelial Cellsin Journal of Immunology179.pp. 1264-1273 Full Text UEA Repository(Article) Cowburn, A. S., Sobolewski, A., Reed, B. J., Deighton, J., Murray, J., Cadwallader, K. A., Bradley, J. R., Chilvers, E. R.(2006)Aminopeptidase N (CD13) Regulates Tumor Necrosis Factor-α-induced Apoptosis in Human Neutrophilsin Journal of Biological Chemistry281.pp. 12458-12467 Full Text UEA Repository(Article) Walmsley, S. R., Print, C., Farahi, N., Peyssonnaux, C., Johnson, R. S., Cramer, T., Sobolewski, A., Condliffe, A. M., Cowburn, A. S., Johnson, N., Chilvers, E. R.(2005)Hypoxia-induced neutrophil survival is mediated by HIF-1α–dependent NF-κB activityin Journal of Experimental Medicine201. Full Text UEA Repository(Article) Sobolewski, A., Jourdan, K. B., Upton, P. D., Long, L., Morrell, N. W.(2004)Mechanism of cicaprost-induced desensitization in rat pulmonary artery smooth muscle cells involves a PKA-mediated inhibition of adenylyl cyclasein AJP: Lung Cellular and Molecular Physiology287.pp. L352-L359 Full Text UEA Repository(Article) Walmsley, S. R., Sheares, K. K. K., Sobolewski, A., Morrell, N. W., Chilvers, E. R.(2004)New insights into oxygen sensing at a cellular levelin Thorax59.pp. 90-92 Full Text(Editorial)Walmsley, S., Cowburn, A., Sobolewski, A., Murray, J., Farahi, N., Sabroe, I., Chilvers, E.(2004)Characterization of the survival effect of tumour necrosis factor-α in human neutrophilsin Biochemical Society Transactions32.pp. 456-460 Full Text UEA Repository(Article)