An investigation of molecular defects underlying impaired acute inflammation in Crohn’s disease
Professor Anthony Segal - Department of Medicine
Description of Project:
Crohn’s disease and Ulcerative colitis are chronic inflammatory disorders of the gastro-intestinal tract affecting approximately 1 in 1000 people in Western populations. The aetiology and pathogenetic mechanisms of these two diseases remain an enigma, although a recent study demonstrated impaired acute inflammatory responses in Crohn’s disease patients. This may result in weak immune responses to intestinal contents that breach the mucosa, and subsequent granuloma formation and chronic inflammation. Additionally, it is known that the presence of certain genetic polymorphisms (such as those found in the NOD2 gene) may predispose to inflammatory bowel disease. This study will aim to further elucidate mechanisms of Crohn’s disease and ulcerative colitis pathogenesis at the cellular and molecular level.
PubMed accessible publications:
Sewell GW, Hannun YA, Han X, Koster G, Bielawski J, Goss V, Smith PJ, Rahman FZ, Vega R, Bloom SL, Walker AP, Postle AD, Segal AW (2012). Lipidomic profiling in Crohn's disease: Abnormalities in phosphatidylinositols, with preservation of ceramide, phosphatidylcholine and phosphatidylserine composition. Int J Biochem Cell Biol.;44(11):1839-1846.
Sewell GW, Rahman FZ, Levine AP, Jostins L, Smith PJ, Walker AP, Bloom SL, Segal AW, Smith AM (2012). Defective tumor necrosis factor release from Crohn's disease macrophages in response to toll-like receptor activation: Relationship to phenotype and genome-wide association susceptibility loci. Inflamm Bowel Dis (Epublished, in press)
Smith PJ, Sewell GW, Levine AP (2011). Endoscopy, but not as we know it. Br J Hosp Med (Lond).;72(3):174
Hayee B, Antonopoulos A, Murphy EJ, Rahman FZ, Sewell G, Smith BN, McCartney S, Furman M, Hall G, Bloom SL, Haslam SM, Morris HR, Boztug K, Klein C, Winchester B, Pick E, Linch DC, Gale RE, Smith AM, Dell A, Segal AW (2011). G6PC3 mutations are associated with a major defect of glycosylation: a novel mechanism for neutrophil dysfunction. Glycobiology. 21(7):914-24
Hayee B, Rahman FZ, Sewell G, Smith AM, Segal AW (2010). Crohn's disease as an immunodeficiency. Expert Rev Clin Immunol.;6(4):585-96.
Marks DJ, Seymour CR, Sewell GW, Rahman FZ, Smith AM, McCartney SA, Bloom SL (2010). Inflammatory bowel diseases in patients with adaptive and complement immunodeficiency disorders Inflamm Bowel Dis.;16(11):1984-92.
Palmer CD, Rahman FZ, Sewell GW, Ahmed A, Ashcroft M, Bloom SL, Segal AW, Smith AM (2009). Diminished macrophage apoptosis and reactive oxygen species generation after phorbol ester stimulation in Crohn's disease. PLoS ONE.;4(11):e7787.
Sewell GW, Marks DJ, Segal AW (2009).The immunopathogenesis of Crohn’s disease: a three-stage model. Curr Opin Immunol.;21(5):506-13.
Smith AM, Rahman FZ, Hayee B, Graham SJ, Marks DJ, Sewell GW, Palmer CD, Wilde J, Foxwell BM, Gloger IS, Sweeting T, Marsh M, Walker AP, Bloom SL, Segal AW (2009). Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease. J Exp Med.;206(9):1883-97
Marks DJ, Rahman FZ, Sewell GW, Segal AW (2009). Crohn’s disease: an Immune Deficiency State. Clin Rev Allergy Immunol. 38(1):20-31
Speaker at UCLH IBD postgraduate course 2012
Tutorials to MBBS Year 2 students (scientific writing and research)
Student representative on the MB PhD Education Committee 2010-2012