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Dr Natalie Burrows

Research Interests

The Hypoxia-Inducible factors (HIF-1 and HIF-2) are transcription factors that mediate oxygen-sensing in cells. In the presence of oxygen, PHD enzymes hydroxylate HIF-α, enabling binding of von-Hippel-Lindau (VHL) protein leading to ubiquitylation and proteosomal degradation. Under low oxygen tensions (hypoxia), hydroxylation is reduced resulting in progressive HIF stabilisation and increased transcription of target genes. Mutations in VHL, PHD2 or HIF2A result in abnormal HIF activation in the presence of oxygen. HIF modulates genes involved in many physiological and pathophysiological processes including angiogenesis, glycolysis, differentiation, apoptosis and cell migration.

This pathway plays a crucial role in innate immunity and inflammation, having significant effects on macrophage behaviour, neutrophil apoptosis and increasing bactericidal activity of myeloid cells. Less is known about the role of HIF in adaptive immune responses. My work focuses on the role of the PHD-VHL-HIF pathway on B cell development and function in mice and humans.

 

Keywords

Immunology ; B cell receptor (BCR) ; B cells ; BCR sequencing ; B cell lineage and repertoire development ; adaptive immunity

Key Publications

  • Early loss of Crebbp confers malignant stem cell properties on lymphoid progenitors. SJ Horton, G Giotopoulos, H Yun, S Vohra, O Sheppard, R Bashford-Rogers, M Rashid, A Clipson, WI Chan, D Sasca, L Yiangou, H Osaki, F Basheer, P Gallipoli, N Burrows, A Erdem, A  Sybirna, S Foerster, W Zhao, T Sustic, A Petrunkina Harrison, E Laurenti, J Okosun, D Hodson, P Wright, KG Smith, P Maxwell, J Fitzgibbon, MQ Du, DJ Adams, BJP Huntly. Nature Cell Biology 19, 1093–1104 (2017)

 

  • N Burrows and PH Maxwell. Hypoxia and B cells. Experimental Cell Research 2017 Mar 12. pii: S0014-4827(17)30124-6

 

  • S Kiriakidis, SS Hoer, N Burrows, G Biddlecome,MN Khan,N Rogers, CJ Schofield, M Botto, E Paleologand PH Maxwell. Complement C1q is hydroxylated by collagen prolyl 4 hydroxylase, and is sensitive to off target inhibition by prolyl hydroxylase domain inhibitors that stabilise Hypoxia Inducible Factor. Kidney international 2017 92, 900–908

Other Publications

  • N Burrows, J Williams, BA Telfer, J Resch, HR Valentine, RJ Fitzmaurice, A Eustace, J Irlam, EJ Rowling, C Hoang-Vu, CM West, G Brabantand KJ Williams. Phosphatidylinositide 3-kinase (PI3K) and PI3K-related kinase (PIKK) activity contributes to radioresistance in thyroid carcinomas. Oncotarget 2016 Aug 04. doi: 10.18632/oncotarget.11056

 

  • RS Al-Lamki, J Wang, J Jang, N Burrows, PH Maxwell, T Eisen, AY Warren, S Vanharanta, S Pacey, P Vandenabeele, JS Pober,and JR Bradley. Tumor necrosis factor receptor 2-signaling in CD133-expressing cells in renal clear cell carcinoma. Oncotarget. 2016 Mar 16. doi: 10.18632/oncotarget.8125

 

  • N Burrows, G Cane, M Robson, E Gaude, W Howat, PW Szlosarek, R Barbara Pedley, C Frezza, M Ashcroft, and PH Maxwell. Hypoxia-induced nitric oxide production and tumour perfusion is inhibited by pegylated arginine deiminase (ADI-PEG20). Scientific reports. 2016; 6:22950

 

  • A Wouters, B Pauwels, N Burrows, M Baay, V Deschoolmeester, TN Vu, K Laukens, P Meijnders, D Van Gestel, KJ Williams, D Van den Weyngaert, JB Vermorken, P Pauwels, M Peeters, F Lardon. The radiosensitising effect of gemcitabine and its main metabolite dFdU under low oxygen conditions is in vitro not dependent on functional HIF-1 protein. BMC Cancer. 2014 Aug 16;14:594

 

  • N Burrows, BA Telfer, G Brabant and KJ Williams. Inhibiting the phosphatidylinositide 3-kinase pathway blocks radiation-induced metastasis associated with Rho-GTPase and Hypoxia inducible factor-1 activity. Radiotherapy and Oncology 2013 Jul 25. pii: S0167-8140(13)00306-X

 

  • C Cawthorne, N Burrows, M Radigois, J Gregory, A Smigova, M Babur, I Wilson, A Danikas, KJ Williams. [18F]-FLT Positron Emission Tomography can be used to image the response of sensitive tumours to PI3-Kinase inhibition with the novel agent GDC-0941. Molecular Cancer Therapeutics 2013 May;12(5):819-28

 

  • RG Gieling, M Babur, L Mamnani, N Burrows, BA Telfer, SR Williams, KE Davies, A Scozzafava, CT Supuran, KJ Williams. Anti-metastatic effect of the sulfonamide carbonic anhydrase IX inhibitor S4 in breast carcinoma xenografts. Journal of Medicinal Chemistry 2012 Jun 14;55 (11): 5591-600

 

  • N Burrows, M Babur, J Resch, S Ridsdale, M Mejin, EJ Rowling, G Brabant and KJ Williams. GDC-0941 inhibits metastatic characteristics of thyroid carcinomas by targeting both the phosphoinositide-3 Kinase (PI3K) and Hypoxia inducible Factor-1α (HIF-1α) pathways. Journal of Clinical Endocrinology & Metabolism Dec 2011 96 (12): E1934–E1943. Research highlight in Nature Reviews Endocrinology 8, 4 (Jan 2012). DOI:10.1038/nrendo.2011.200

 

  • N Burrows, M Babur, J Resch, KJ Williams and G Brabant. Hypoxia-inducible Factor (HIF) in thyroid carcinoma. Journal of Thyroid Research 2011; 762905

 

  • N Burrows, J Resch, RL Cowen, R von Wasielewski, C. Hoang-Vu, CM West, KJ Williams and G Brabant. Expression of hypoxia-inducible factor 1α in thyroid carcinomas. Endocrine-related cancer 2010; 17:61–72