Anastasia Sobolewski

Career-track Research Leader

Contact Details:

Institute of Food Research,
Norwich Research Park,
Colney, Norwich,
NR4 7UA
UK
+44 (0)1603 255243
anastasia.sobolewski@ifr.ac.uk

Research interests

A number of observations have implicated abnormal host-microbial interactions in the pathogenesis of idiopathic inflammatory bowel diseases - Crohn's disease and ulcerative colitis (Sartor, Gastroenterology 134, 577 2008. Baumgart, Carding, Lancet 369, 1627 2007). In normal hosts, commensal bacteria activate a programme of finely-tuned immune responses by epithelial cells, macrophages, dendritic cells, T lymphocytes, and plasma B cells to maintain intestinal homeostasis. The colonic epithelium forms a physical barrier to exclude bacteria and their biologically active products from interacting with mucosal immune cells. Epithelial integrity is maintained by processes of constant renewal and repair in response to injury/infection. The epithelium can also act as an innate immune sensor of microbial pathogens (Singh Am J Physiol. 288 G514-24 2005.). Bacterial components are recognised by Toll-like receptors (TLR) on epithelial and immune cells (e.g. macrophages, neutrophils etc.) or by intracellular NOD2 receptors (Strober, Nat Rev Immunol 6, 9 (2006); Girardin, J Biol Chem 278, 8869 2003).  Recent bio-imaging experiments have suggested that recognition of bacterial structures or mucosal injury is followed by recruitment of immune cells to specific sites at the epithelium (Chieppa J Exp Med 203, 2841 2006., Pull, Proc Natl Acad Sci 102(1):99-104 2005).

The hypothesis for this work is that dynamic remodelling of microbial-immune-epithelial cell interactions is required for homeostasis/regeneration of the colonic epithelium

We have a variety of experimental model systems in the Sobolewski laboratory including intestinal organoid/crypt-,mucosal colonic explant- and innate  immune cell- culture.  We also use immunoflourescence and bio-imaging (confocal and multiphoton microscopy) to study the microbial-epithelial-immune cell interactions in the intestine.

FULL PAPERS
1. Farahi N, Uller L, Juss JK, Langton AJ, Cowburn AS, Gibson A, Foster MR, Farrow SN, Marco-Casanova P, Sobolewski A, Condliffe AM, Chilvers Effects of the cyclin-dependent kinase inhibitor R-roscovitine on eosinophil survival and clearance ER Clin Exp Allergy. 2011 May;41(5):673-87                                                                 2. A. Sobolewski, N. Rudarakanchana, P.D. Upton, J. Yang, T. K. Crilley, R. Trembath, N. W. Morrell. Functional rescue of mutant bone morphogenetic protein receptor type II in pulmonary arterial hypertension. Human Molecular Genetics, 2008 oct 15;17(20):3180-90.
3. J. Yang, M. Southwood, Paul Upton, L. Long, X. Yang, N. Rudarakanchana, A. Sobolewski, Richard Trembath and Nick Morrell. Regulation of Id gene expression by MAPK and Smad1/5 pathways in pulmonary artery smooth muscle cells. Circulation Research. 2008;102:1212-1221.
4. N. Farahi, A. S. Cowburn, P. D. Upton, J. Deighton, A. Sobolewski, E. Gherardi, N. W. Morrell, and E. R. Chilvers. The Journal of Immunology 2007 Jul 15;179(2):1264-73.Eotaxin-1/CC Chemokine Ligand 11: A Novel Eosinophil Survival Factor Secreted by Human Pulmonary Artery Endothelial Cells.
5. Cowburn AS, Sobolewski A, Reed BJ, Deighton J, Murray J, Cadwallader KA, Bradley JR, Chilvers ER Joournal of Biological Chemistry 2006 May 5;281(18):12458-67. Aminopeptidase N (CD13) regulates tumor necrosis factor-alpha-induced apoptosis in human neutrophils.
6. S. R. Walmsley, C. Print, N. Farahi, C. Peyssonnaux, R. S. Johnson, T. Cramer, A. Sobolewski, A. M. Condliffe, A. S. Cowburn, N. Johnson, and E. R. Chilvers. The Journal of Experimental Medicine, Volume 201, Number 1, 105-115, 2005. Hypoxia-induced neutrophil survival is mediated by HIF-1 -dependent NF- B activity.
7. A. Sobolewski, K. B. Jourdan, P. D. Upton, L. Long, and N. W. Morrell. The American Journal of Physiology Lung Cellular Molecular Physiology 287: L352-L359, 2004. Mechanism of cicaprost-induced desensitization in rat pulmonary artery smooth muscle cells involves a PKA-mediated inhibition of adenylyl cyclase.
8. S.R. Walmsley, A.S. Cowburn, A. Sobolewski, J. Murray, N. Farahi, I. Sabroe and E.R. Chilvers. Biochem. Soc. Trans. (2004) 32, (456-460) Characterization of the survival effect of tumour necrosis factor-Ą in human neutrophils
9. S. R. Walmsley, K. K. K. Sheares, A. Sobolewski, N. W. Morrell and E. R. Chilvers. Thorax 2004;59:90-92 New insights into oxygen sensing at a cellular level
Paper 6 was accompanied by an editorial in The journal of Experimental Medicine : Surviving Low Oxygen