Contact Details:

l.a.metherell@qmul.ac.uk

Lou Metherell graduated from the University of Manchester in 1985 with a degree in Biology. She was awarded her PhD from the University of Greenwich in 1999 for her work on rapid PCR methods for the identification of bacterial pathogens. She joined the Endocrinology department in 1998 and her research has focussed on the genetics of endocrine disease. In 2008 she was awarded a New Investigator Research Grant from the MRC which has enabled her to continue her research into the genetic causes of Familial Glucocorticoid Deficiency. She was appointed to a lectureship in 2009.

Current research interest

My research interests include:

1. Genetics of Familial Glucocorticoid Deficiency (FGD). Following on from the work of Professor Adrian Clark in identifying the melanocortin receptor (MC2R) as the first cause of FGD, Dr Metherell discovered mutations in its accessory protein (MRAP) are also implicated in the disease. Recent research has identified a third aetiology, subtle defects in the steroidogenic acute regulatory protein (StAR) cause FGD in a minority (<10%) of patients. Current studies are focussed on identifying further genes involved in MC2R function by both genetic and proteomic approaches.
   
   
   
2. Genetics of Growth She maintains an interest in childhood growth disorders, particularly in defects of the growth hormone receptor (GHR) pathway. In conjunction with Professor Martin Savage she has described many novel defects in the growth hormone receptor, the most significant of which was the identification of pseudoexon inclusion as a novel disease mechanism. Defects in other genes in the pathway, such as STAT5B and the acid labile subunit, IGFALS, have also been identified.
   

Key publications

• David A, Miraki-Moud F, Shaw NJ, Savage MO, Clark AJ, Metherell LA. (2010) Identification and characterisation of a novel GHR defect disrupting the polypyrimidine tract and resulting in GH insensitivity. Eur J Endocrinol. 162:37-42.
  
  
  
• Metherell LA, Naville D, Halaby G, Begeot M, Huebner A, Nürnberg G, Nürnberg P, Green J, Tomlinson JW, Krone NP, Lin L, Racine M, Berney DM, Achermann JC, Arlt W, Clark AJL. (2009) Non-classic lipoid congenital adrenal hyperplasia masquerading as familial glucocorticoid deficiency. 94:3865-71.
  
  
• Chan LF, Webb TR, Chung T-T, Meimaridou E, Cooray SN, Guasti L, Chapple JP, , Egertová M, Elphick MR, Cheetham ME, Metherell LA and Clark AJL. (2009) MRAP and MRAP2 are bidirectional regulators of the Melanocortin receptor family. Proceedings of the National Academy of Sciences USA 106: 6146-51.
  
  
  
• Metherell LA, Chapple JP, Cooray S, David A, Becker C, Rüschendorf F, Naville D, Begeot M, Khoo B, Nürnberg P, Huebner A, Cheetham ME & Clark AJL. (2005) Mutations in MRAP, encoding a novel interacting partner of the ACTH receptor, cause Familial Glucocorticoid Deficiency Type 2. Nature Genetics 37: 166 -170.
  
  
  
• Chung TT, Webb TR, Chan LF, Cooray SN, LA Metherell, King PJ, Chapple JP and Clark AJL (2008) The majority of ACTH receptor mutations found in Familial Glucocorticoid Deficiency type 1 lead to defective trafficking of the receptor to the cell surface. Journal of Clinical Endocrinology and Metabolism 93:4948-4954.
  
  
  
• David A, Camacho-Hubner C, Bhangoo A, Rose SJ, Miraki-Moud F, Akker SA, Butler GE, Ten S, Clayton PE, Clark AJ, Savage MO, Metherell LA. (2007) An intronic growth hormone receptor mutation causing activation of a pseudoexon is associated with a broad spectrum of growth hormone insensitivity phenotypes. J Clin Endocrinol Metab. 92:655-9.
  
  
  
• Metherell LA, Savage MO, Dattani M, Walker J, Clayton PE, Farooqi IS, Clark AJ. (2004) TPIT mutations are associated with early-onset, but not late-onset isolated ACTH deficiency. Eur J Endocrinol. 151:463-5.
  
  
  
• Milward A, Metherell L, Maamra M, Barahona MJ, Wilkinson IR, Camacho-Hubner C, Savage MO, Bidlingmaier CM, Clark AJ, Ross RJ, Webb SM. (2004) Growth hormone (GH) insensitivity syndrome due to a GH receptor truncated after Box1, resulting in isolated failure of STAT 5 signal transduction. J Clin Endocrinol Metab. 89:1259-66.
  
  
• Metherell LA, Akker SA, Munroe PB, Rose SJ, Savage MO, Chew SL & Clark AJL. (2001) Pseudoexon activation as a novel mechanism for disease resulting in atypical growth hormone insensitivity. American Journal of Human Genetics 69: 641 - 646.