Flanagan, Sarah - University of Exeter

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Following graduation from the University of Bristol in 2003 Sarah joined the monogenic diabetes research team at the Peninsula Medical school. In 2005 she started her PhD under the supervision of Professors Andrew Hattersley and Sian Ellard and 2 years later submitted her thesis which contained 6 peer-reviewed papers reporting novel genotype/phenotype relationships in neonatal diabetes and congenital hyperinsulinism. On completion of her doctoral studies Sarah was awarded the Sir Bob Wilkins, Peninsula Medical School, Fellowship. This funding allowed her to continue research investigating the genetic basis of neonatal diabetes and enabled her to spend time with Dr Deborah Mackay (University of Southampton) at the Wessex Regional Genetics laboratory learning techniques for the molecular diagnosis of transient neonatal diabetes due to defects in methylation at chromosome 6q24. In 2008 Sarah received a Heredity Fieldwork Grant from the Genetics Society which funded a secondment to the Department of Physiology, Anatomy and Genetics at the University of Oxford. Under the supervision of Professor Frances Ashcroft Sarah undertook electrophysiology studies on mutant K-ATP channels expressed in Xenopus oocytes. Sarah worked as a post-doctoral research fellow for 7 years on Wellcome Trust and Medical Research Council funded project grants investigating the genetic basis of neonatal diabetes and congenital hyperinsulinism. During this period she published >125 research papers in international journals (23 first author or senior author) on these opposing disorders of insulin secretion. As part of the monogenic diabetes research team in Exeter Sarah has contributed to the discovery of 9 of the 20 known genetic causes of permanent neonatal diabetes and was lead author for 3 of these genes (Flanagan et al. Cell Metab 2014, Flanagan et al. Nat Genet 2014). Her work on the discovery of recessive MNX1 and NKX2-2 mutations causing neonatal diabetes was short-listed for the Junior Research Prize at the 2011 EASD SGGD meeting. In 2014 Sarah was awarded a Sir Henry Dale Fellowship to take forward her work on gene discovery in congenital hyperinsulinaemic hypoglycaemia. This work complements the neonatal diabetes research being undertaken in Exeter which shares many biological mechanisms and pathways with congenital hyperinsulinism and promises to yield important findings about mechanisms of insulin secretion. Further details regarding her research can be found on her laboratory website, Qualifications PhD: Molecular Genetics, Peninsula Medical School (2005-2007) BSc (hons): Cancer Biology and Immunology, University of Bristol (2000-2003)

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Ellard S, Flanagan SE, De Franco E, Lango Allen H, Zera M, Abdul-Rasoul MM, Edge Julie A, Stewart H, Alamiri E, Hussain K, et al (In Press). Analysis of transcription factors central for mouse pancreatic development establish NKX2-2 and MNX1 mutations as novel causes of neonatal diabetes in man. Cell Meatabolism Full text. Hattersley AT, Globa E, Zelinska N, Mackay DJ, Temple KI, Houghton JA, Flanagan SE, Ellard S (In Press). Neonatal diabetes in Ukraine: incidence, genetics, clinical phenotype and treatment. Journal of Pediatric Endocrinoyl Metabolism Full text. Güven A, Cebeci AN, Ellard S, Flanagan SE (2016). Clinical and genetic characteristics, management and long-term follow-up of turkish patients with congenital hyperinsulinism. JCRPE Journal of Clinical Research in Pediatric Endocrinology, 8(2), 197-204. Abstract. Çamtosun E, Flanagan SE, Ellard S, Siklar Z, Hussain K, Kocaay P, Berberoglu M (2015). A deep intronic HADH splicing mutation (c.636+471G>T) in a congenital hyperinsulinemic hypoglycemia case: Long term clinical course. JCRPE Journal of Clinical Research in Pediatric Endocrinology, 7(2), 144-147. Abstract. Full text. Harel S, Cohen ASA, Hussain K, Flanagan SE, Schlade-Bartusiak K, Patel M, Courtade J, Li JBW, Van Karnebeek C, Kurata H, et al (2015). Alternating hypoglycemia and hyperglycemia in a toddler with a homozygous p.R1419H ABCC8 mutation: an unusual clinical picture. Journal of Pediatric Endocrinology and Metabolism, 28(3-4), 345-351. Abstract. Sansbury FH, Kirel B, Caswell R, Lango Allen H, Flanagan SE, Hattersley AT, Ellard S, Shaw-Smith CJ (2015). Biallelic RFX6 mutations can cause childhood as well as neonatal onset diabetes mellitus. European Journal of Human Genetics, 23(12), 1744-1748. Abstract. Article has an altmetric score of 11 Sansbury FH, Kirel B, Caswell R, Allen HL, Flanagan SE, Hattersley AT, Ellard S, Shaw-Smith CJ (2015). Biallelic RFX6 mutations can cause childhood as well as neonatal onset diabetes mellitus. Eur J Hum Genet, 23(12), 1744-1748. Abstract. Author URL. Full text. Article has an altmetric score of 11 Demirbilek H, Arya VB, Ozbek MN, Houghton JA, Baran RT, Akar M, Tekes S, Tuzun H, Mackay DJ, Flanagan SE, et al (2015). Clinical characteristics and molecular genetic analysis of 22 patients with neonatal diabetes from the South-Eastern region of Turkey: predominance of non-KATP channel mutations. Eur J Endocrinol, 172(6), 697-705. Abstract. Author URL. Full text. Abraham MB, Shetty VB, Price G, Smith N, Bock MD, Siafarikas A, Resnick S, Whan E, Ellard S, Flanagan SE, et al (2015). Efficacy and safety of sirolimus in a neonate with persistent hypoglycaemia following near-total pancreatectomy for hyperinsulinaemic hypoglycaemia. Journal of Pediatric Endocrinology and Metabolism, 28(11-12), 1391-1398. Abstract. Senniappan S, Sadeghizadeh A, Flanagan SE, Ellard S, Hashemipour M, Hosseinzadeh M, Salehi M, Hussain K (2015). Genotype and phenotype correlations in Iranian patients with hyperinsulinaemic hypoglycaemia. BMC Res Notes, 8 Abstract. Author URL. Full text. Shi Y, Avatapalle HB, Skae MS, Padidela R, Newbould M, Rigby L, Flanagan SE, Ellard S, Rahier J, Clayton PE, et al (2015). Increased plasma incretin concentrations identifies a subset of patients with persistent congenital hyperinsulinism without KATP channel gene defects. J Pediatr, 166(1), 191-194. Abstract. Author URL. Article has an altmetric score of 13 Habeb AM, Deeb A, Johnson M, Abdullah M, Abdulrasoul M, Al-Awneh H, Al-Maghamsi MSF, Al-Murshedi F, Al-Saif R, Al-Sinani S, et al (2015). Liver disease and other comorbidities in Wolcott-Rallison syndrome: Different phenotype and variable associations in a large cohort. Hormone Research in Paediatrics, 83(3), 190-197. Abstract. Full text. Article has an altmetric score of 1 Russell MA, Flanagan SE, Ellard S, Otonkoski T, Hattersley AT, Morgan NG (2015). Molecular investigation of the K392R mutant form of STAT3 found in a patient with early-onset autoimmune diabetes. DIABETIC MEDICINE, 32, 64-64. Author URL. Khawash P, Hussain K, Flanagan SE, Chatterjee S, Basak D (2015). Nifedipine in Congenital Hyperinsulinism-A Case Report. JOURNAL OF CLINICAL RESEARCH IN PEDIATRIC ENDOCRINOLOGY, 7(2), 151-154. Author URL. Full text. Article has an altmetric score of 1 Babiker O, Flanagan SE, Ellard S, Girim HA, Hussain K, Senniappan S (2015). Protein-induced hyperinsulinaemic hypoglycaemia due to a homozygous HADH mutation in three siblings of a Saudi family. Journal of Pediatric Endocrinology and Metabolism, 28(9-10), 1073-1077. Abstract. Shah P, Arya VB, Flanagan SE, Morgan K, Ellard S, Senniappan S, Hussain K (2015). Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation. Journal of Pediatric Endocrinology and Metabolism, 28(5-6), 695-699. Abstract. De Franco E, Flanagan SE, Houghton JAL, Allen HL, MacKay DJG, Temple IK, Ellard S, Hattersley AT (2015). The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study. The Lancet, 386(9997), 957-963. Abstract. Article has an altmetric score of 93 De Franco E, Flanagan SE, Houghton JA, Lango Allen H, Mackay DJ, Temple IK, Ellard S, Hattersley AT (2015). The effect of early, comprehensive genomic testing on clinical care in neonatal diabetes: an international cohort study. Lancet, 386(9997), 957-963. Abstract. Author URL. Full text. Article has an altmetric score of 93 Çamtosun E, Siklar Z, Kocaay P, Ceylaner S, Flanagan SE, Ellard S, Berbero?lu M (2015). Three cases of Wolfram syndrome with different clinical aspects. Journal of Pediatric Endocrinology and Metabolism, 28(3-4), 433-438. Abstract. Article has an altmetric score of 1 Durmaz E, Flanagan SE, Parlak M, Ellard S, Akcurin S, Bircan I (2014). A combination of nifedipine and octreotide treatment in an hyperinsulinemic hypoglycemic infant. JCRPE Journal of Clinical Research in Pediatric Endocrinology, 6(2), 119-121. Abstract. Full text.

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