Prof Lou Metherell

BSc PhD

Professor of Endocrine Genetics

Centre for Endocrinology, William Harvey Research Institute
Faculty of Medicine and Dentistry, Queen Mary University of London

l.a.metherell@qmul.ac.uk
www.qmul.ac.uk/whri/people/academic-staff/items/metherelllou.html

Research
Publications
Grants

Research

Genetics, Adrenal insufficiency, Endocrinology, Cardiomyopathy, Growth retardation

Cardiovascular Models, Skin Models

Interests

My group has an interest in in vitro modelling tissues for several aspects of my research; 3D models of skin to understand the ichthyosis seen in sphingosine-1-phosphate lyase deficiency, a multi-organ pathology also involving adrenal insufficiency, steroid resistant nephrosis and neurological deficits. To study the development and maintenance of the adrenal cortex, to try and understand what goes wrong in syndromes of adrenal insufficiency.

Publications

Publications of specific relevance to Predictive in vitro Models

2021

Farooqi N, Metherell LA, Schrauwen I, Acharya A, Khan Q, Nouel Saied LM, Ali Y, El-Serehy HA, Jalil F and Leal SM (2021). Exome sequencing identifies a novel fbn1 variant in a pakistani family with marfan syndrome that includes left ventricle diastolic dysfunction. Genes vol. 12, (12) 10.3390/genes12121915

Smith CJ, Williams JL, Caley MP, O’Toole EA, Prasad R and Metherell LA (2021). 099 Ichthyosis associated with sphingosine 1-phosphate lyase deficiency is due to aberrant calcium and sphingolipid regulation. Journal of Investigative Dermatology vol. 141, (10) s165-s165. 10.1016/j.jid.2021.08.102

Zhou J, Azizan EAB, Cabrera CP, Fernandes-Rosa FL, Boulkroun S, Argentesi G, Cottrell E, Amar L, Wu X, O’Toole S, Goodchild E, Marker A, Senanayake R, Garg S, Åkerström T, Backman S, Jordan S, Polubothu S, Berney DM, Gluck A, Lines KE, Thakker RV, Tuthill A, Joyce C, Kaski JP, Karet Frankl FE, Metherell LA, Teo AED, Gurnell M and Parvanta L (2021). Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause. Nature Genetics 10.1038/s41588-021-00906-y

Argentesi G, Azizan E, Zhou J, Cabrera C, O’Toole S, Wu X, Goodchild E, Cottrell E, Marker A, Senanayake R, Garg S, Jordan S, Berney D, Gluck A, Lines K, Thakker RV, Tuthill A, Joyce C, Karet FF, Metherell L, Teo A, Gurnell M, Parvanta L, Drake W, Wozniak E, Mein C, Kinsler V, Storr H and Brown M (2021). Somatic mutations of GNA11 and GNAQ in CTNNB1-mutant aldosterone-producing adenomas presenting in puberty, pregnancy or menopause. Nature Research Nature Genetics 10.1038/s41588-021-00906-y

Buonocore F, Maharaj A, Qamar Y, Koehler K, Suntharalingham JP, Chan LF, Ferraz-De-Souza B, Hughes CR, Lin L, Prasad R, Allgrove J, Andrews ET, Buchanan CR, Cheetham TD, Crowne EC, Davies JH, Gregory JW, Hindmarsh PC, Hulse T, Krone NP, Shah P, Shaikh MG, Roberts C, Clayton PE, Dattani MT, Thomas NS, Huebner A, Clark AJ, Metherell LA and Achermann JC (2021). Genetic Analysis of Pediatric Primary Adrenal Insufficiency of Unknown Etiology: 25 Years' Experience in the UK. Journal of The Endocrine Society vol. 5, (8) 10.1210/jendso/bvab086

Cottrell E, Maharaj A, Williams J, Chatterjee S, Cirillo G, Miraglia Del Giudice E, Festa A, Palumbo S, Capalbo D, Salerno M, Pignata C, Savage MO, Schilbach K, Bidlingmaier M, Hwa V, Metherell LA, Grandone A and Storr HL (2021). Growth Hormone Receptor (Ghr) 6ω Pseudoexon Activation: A Novel Cause Of Severe Growth Hormone Insensitivity (Ghi). J Clin Endocrinol Metab 10.1210/clinem/dgab550

Cottrell E, Maharaj A, Williams J, Chatterjee S, Cirillo G, Miraglia Del Giudice E, Festa A, Palumbo S, Capalbo D, Salerno M, Pignata C, Savage MO, Schilbach K, Bidlingmaier M, Hwa V, Metherell LA, Grandone A and Storr HL (2021). Growth Hormone Receptor (GHR) 6Ω Pseudoexon Activation: a Novel Cause of Severe Growth Hormone Insensitivity. J Clin Endocrinol Metab 10.1210/clinem/dgab550

Andrews A, Maharaj A, Cottrell E, Chatterjee S, Shah P, Denvir L, Dumic K, Bossowski A, Mushtaq T, Vukovic R, Didi M, Shaw N, Metherell LA, Savage MO and Storr HL (2021). Genetic Characterization of Short Stature Patients with Overlapping Features of Growth Hormone Insensitivity Syndromes. Journal of Clinical Endocrinology and Metabolism vol. 106, (11) E4716-E4733. 10.1210/clinem/dgab437

Williams JL, Hall CL, Meimaridou E and Metherell LA (2021). Loss of nnt increases expression of oxidative phosphorylation complexes in c57bl/6j hearts. International Journal of Molecular Sciences vol. 22, (11) 10.3390/ijms22116101

Kwong RMW, Maharaj AV, Metherell L and Prasad R (2021). Sphingosine 1- Phosphate Lyase Insufficiency Syndrome (SPLIS); A Role in Multiple Endocrinopathies. Journal of The Endocrine Society vol. 5, (Suppl 1) a662-a662. 10.1210/jendso/bvab048.1351

Azizan EAB, Zhou J, Cabrera CP, Fernandes-Rosa FL, Boulkroun S, Argentesi G, Cottrell E, Amar L, Wu X, Marker A, Garg S, Akerstrom T, Backman S, Jordan S, Gluck AK, Lines KE, Thakker RV, Tuthill AA, Joyce CM, Metherell L, Teo A, Gurnell M, Parvanta L, Drake W, Wozniak E, Kuan JL, Tiang Z, Hellman P, Foo R and Mein C (2021). Somatic Mutations of GNA11 and GNAQ in CTNNB1-Mutant Aldosterone-Producing Adenomas Increases Aldosterone and Aldosterone Synthase (CYP11B2). Journal of The Endocrine Society vol. 5, (Supplement_1) a72-a72. 10.1210/jendso/bvab048.145

Zhou J, Boulkroun S, Cabrera CP, Azizan EAB, Fernandes-Rosa F, Cottrell E, Argentesi G, Wu X, O’Toole S, Marker A, Jordan S, Berney DM, Lines K, Metherell L, Teo A, Thakker RV, Drake W, Wozniak E, Mein CA, Storr HL, Zennaro M-C and Brown MJ (2021). CTNNB1-Mutant Aldosterone-Producing Adenomas With Somatic Mutations of GNA11/GNAQ Have Distinct Phenotype and Genotype. Journal of The Endocrine Society vol. 5, (Suppl 1) a65-a66. 10.1210/jendso/bvab048.133

Smith C, Maharaj AV, Qamar Y, Read J, Williams J, Chan L, Marimuthu V and Metherell L (2021). In Vitro Splicing Assay Proves the Pathogenicity of Intronic Variants in MRAP. Journal of The Endocrine Society vol. 5, (Suppl 1) a85-a86. 10.1210/jendso/bvab048.172

Maudhoo A, Maharaj A, Buonocore F, Martos-Moreno GA, Argente J, Achermann JC, Chan LF and Metherell LA (2021). Missplicing due to a synonymous, t96= exonic substitution in the t-box transcription factor tbx19 resulting in isolated acth deficiency. Endocrinology, Diabetes and Metabolism Case Reports vol. 2021, (1) 10.1530/EDM-21-0128

2020

Cottrell E, Cabrera CP, Ishida M, Chatterjee S, Greening J, Wright N, Bossowski A, Dunkel L, Deeb A, Basiri IA, Rose SJ, Mason A, Bint S, Ahn JW, Hwa V, Metherell LA, Moore GE and Storr HL (2020). Rare CNVs provide novel insights into the molecular basis of GH and IGF-1 insensitivity. European Journal of Endocrinology vol. 163, (6) 581-595. 10.1530/EJE-20-0474

Maharaj A, Williams J, Bradshaw T, Güran T, Braslavsky D, Casas J, Chan LF, Metherell LA and Prasad R (2020). Sphingosine-1-phosphate lyase (SGPL1) deficiency is associated with mitochondrial dysfunction. J Steroid Biochem Mol Biol vol. 202, 10.1016/j.jsbmb.2020.105730

Maharaj A, Theodorou D, Banerjee I, Metherell LA, Prasad R and Wallace D (2020). A Sphingosine-1-Phosphate Lyase Mutation Associated With Congenital Nephrotic Syndrome and Multiple Endocrinopathy. Frontiers in Pediatrics vol. 8, 10.3389/fped.2020.00151

Zhou J, Cabrera CP, Azizan EAB, Fernandes-Rosa F, Cottrell E, Amar L, Argentesi G, Wu X, Marker A, Jordan S, Polubothu S, Berney DM, Tuthill A, Karet FE, Metherell L, Teo A, Thakker RV, Drake W, Boulkroun S, Kinsler V, Storr HL, Zennaro M-C and Brown MJ (2020). SAT-224 Recurrent Co-Driver Mutation in CTNNB1-Mutant Aldosterone-producing Adenomas (APA), Causing Reversible Hypertension in Puberty, Pregnancy or Menopause. Journal of The Endocrine Society vol. 4, (Suppl 1) A624-A624. 10.1210/jendso/bvaa046.1231

Williams JL, Paudyal A, Awad S, Nicholson J, Grzesik D, Botta J, Meimaridou E, Maharaj AV, Stewart M, Tinker A, Cox RD and Metherell LA (2020). Mylk3 null c57bl/6n mice develop cardiomyopathy, whereas nnt null c57bl/6j mice do not. Life Science Alliance vol. 3, (4) 10.26508/LSA.201900593

Kallali W, Gray E, Mehdi MZ, Lindsay R, Metherell LA, Buonocore F, Suntharalingham JP, Achermann JC and Donaldson M (2020). Long-term outcome of partial P450 side-chain cleavage enzyme deficiency in three brothers: The importance of early diagnosis. Bioscientifica European Journal of Endocrinology vol. 182, (3) K15-K24. 10.1530/EJE-19-0696

Chatterjee S, Cottrell E, Rose SJ, Mushtaq T, Maharaj AV, Williams J, Savage MO, Metherell LA and Storr HL (2020). GHR gene transcript heterogeneity may explain phenotypic variability in GHR pseudoexon (6Ψ) patients. Endocrine Connections vol. 9, (3) 211-222. 10.1530/EC-20-0026

2019

Novoselova TV, King PJ, Guasti L, Metherell LA, Clark AJL and Chan LF (2019). ACTH signalling and adrenal development: Lessons from mouse models. Endocrine Connections vol. 8, (7) R122-R130. 10.1530/EC-19-0190

Maharaj A, Maudhoo A, Chan LF, Novoselova T, Prasad R, Metherell LA and Guasti L (2019). Isolated glucocorticoid deficiency: Genetic causes and animal models. Journal of Steroid Biochemistry and Molecular Biology vol. 189, 73-80. 10.1016/j.jsbmb.2019.02.012

Storr HL, Chatterjee S, Metherell LA, Foley C, Rosenfeld RG, Backeljauw PF, Dauber A, Savage MO and Hwa V (2019). Nonclassical GH insensitivity: Characterization of mild abnormalities of GH action. Endocrine Reviews vol. 40, (2) 476-505. 10.1210/er.2018-00146

Settas N, Persky R, Faucz FR, Sheanon N, Voutetakis A, Lodish M, Metherell LA and Stratakis CA (2019). SGPL1 deficiency: A rare cause of primary adrenal insufficiency. Journal of Clinical Endocrinology and Metabolism vol. 104, (5) 1484-1490. 10.1210/jc.2018-02238

Maharaj A, Buonocore F, Meimaridou E, Ruiz-Babot G, Guasti L, Peng HM, Capper CP, Burgos-Tirado N, Prasad R, Hughes CR, Maudhoo A, Crowne E, Cheetham TD, Brain CE, Suntharalingham JP, Striglioni N, Yuksel B, Gurbuz F, Gupta S, Lindsay R, Couch R, Spoudeas HA, Guran T, Johnson S, Fowler DJ, Conwell LS, McInerney-Leo AM, Drui D, Cariou B and Lopez-Siguero JP (2019). Predicted benign and synonymous variants in CYP11A1 cause primary adrenal insufficiency through missplicing. Journal of The Endocrine Society vol. 3, (1) 201-221. 10.1210/js.2018-00130

2018

Klammt J, Neumann D, Gevers EF, Andrew SF, Schwartz ID, Rockstroh D, Colombo R, Sanchez MA, Vokurkova D, Kowalczyk J, Metherell LA, Rosenfeld RG, Pfäffle R, Dattani MT, Dauber A and Hwa V (2018). Dominant-negative STAT5B mutations cause growth hormone insensitivity with short stature and mild immune dysregulation. Nature Communications vol. 9, (1) 10.1038/s41467-018-04521-0

Novoselova TV, Hussain M, King PJ, Guasti L, Metherell LA, Charalambous M, Clark AJL and Chan LF (2018). MRAP deficiency impairs adrenal progenitor cell differentiation and gland zonation. Faseb Journal vol. 32, (11) 6186-6196. 10.1096/fj.201701274RR

Howard SR, Oleari R, Poliandri A, Chantzara V, Fantin A, Ruiz-Babot G, Metherell LA, Cabrera CP, Barnes MR, Wehkalampi K, Guasti L, Ruhrberg C, Cariboni A and Dunkel L (2018). HS6ST1 Insufficiency Causes Self-Limited Delayed Puberty in Contrast with Other GnRH Deficiency Genes. Journal of Clinical Endocrinology and Metabolism vol. 103, (9) 3420-3429. 10.1210/jc.2018-00646

Chortis V, Taylor AE, Doig CL, Walsh MD, Meimaridou E, Jenkinson C, Rodriguez-Blanco G, Ronchi CL, Jafri A, Metherell LA, Hebenstreit D, Dunn WB, Arlt W and Foster PA (2018). Nicotinamide nucleotide transhydrogenase as a novel treatment target in adrenocortical carcinoma. Endocrinology vol. 159, (8) 2836-2849. 10.1210/en.2018-00014

Chatterjee S, Shapiro L, Rose SJ, Mushtaq T, Clayton PE, Ten SB, Bhangoo A, Kumbattae U, Dias R, Savage MO, Metherell LA and Storr HL (2018). Phenotypic spectrum and responses to recombinant human IGF1 (rhIGF1) therapy in patients with homozygous intronic pseudoexon growth hormone receptor mutation. European Journal of Endocrinology vol. 178, (5) 481-489. 10.1530/EJE-18-0042

Ruiz-Babot G, Balyura M, Hadjidemetriou I, Ajodha SJ, Taylor DR, Ghataore L, Taylor NF, Schubert U, Ziegler CG, Storr HL, Druce MR, Gevers EF, Drake WM, Srirangalingam U, Conway GS, King PJ, Metherell LA, Bornstein SR and Guasti L (2018). Modeling Congenital Adrenal Hyperplasia and Testing Interventions for Adrenal Insufficiency Using Donor-Specific Reprogrammed Cells. Cell Reports vol. 22, (5) 1236-1249. 10.1016/j.celrep.2018.01.003

Meimaridou E, Goldsworthy M, Chortis V, Fragouli E, Foster PA, Arlt W, Cox R and Metherell LA (2018). NNT is a key regulator of adrenal redox homeostasis and steroidogenesis in male mice. Journal of Endocrinology vol. 236, (1) 13-28. 10.1530/JOE-16-0638

2017

Shapiro L, Chatterjee S, Ramadan DG, Davies KM, Savage MO, Metherell LA and Storr HL (2017). Whole-exome sequencing gives additional benefits compared to candidate gene sequencing in the molecular diagnosis of children with growth hormone or IGF-1 insensitivity. European Journal of Endocrinology vol. 177, (6) 485-501. 10.1530/EJE-17-0453

Salvatori R, Radian S, Diekmann Y, Iacovazzo D, David A, Gabrovska P, Grassi G, Bussell A-M, Stals K, Weber A, Quinton R, Crowne EC, Corazzini V, Metherell L, Kearney T, Du Plessis D, Sinha AK, Baborie A, Lecoq A-L, Chanson P, Ansorge O, Ellard S, Trainer PJ, Balding D, Thomas MG and Korbonits M (2017). In-frame seven amino-acid duplication in AIP arose over the last 3000 years, disrupts protein interaction and stability and is associated with gigantism. Eur J Endocrinol vol. 177, (3) 257-266. 10.1530/EJE-17-0293

Wacharasindhu S, Panamonta O, Shapiro L, Metherell LA, Savage MO and Storr HL (2017). Young Thai sisters with growth hormone insensitivity or Laron syndrome. Asian Biomedicine vol. 11, (2) 167-170. 10.5372/1905-7415.1102.549

Vairamani K, Merjaneh L, Casano-Sancho P, Sanli ME, David A, Metherell LA, Savage MO, Del Pozo JS, Backeljauw PF, Rosenfeld RG, Aisenberg J, Dauber A and Hwa V (2017). Novel Dominant-Negative GH Receptor Mutations Expands the Spectrum of GHI and IGF-I Deficiency. Oxford University Press J Endocr Soc vol. 1, (4) 345-358. 10.1210/js.2016-1119

METHERELL LA, Prasad R, Storr HL, Guasti L, Maharaj A, Meimaridou E and Hadjidemetriou I (2017). Sphingosine-1-phosphate lyase mutations cause primary adrenal insufficiency and steroid-resistant nephrotic syndrome. American Society For Clinical Investigation Journal of Clinical Investigation 10.1172/JCI90171

2016

Metherell LA, Guerra-Assunção JA, Sternberg MJ and David A (2016). Three-Dimensional Model of Human Nicotinamide Nucleotide Transhydrogenase (NNT) and Sequence-Structure Analysis of its Disease-Causing Variations. Human Mutation vol. 37, (10) 1074-1084. 10.1002/humu.23046

HOWARD SR, Guasti L, Ruiz-Babot G, Mancini A, David A, Storr H, Metherell LA, Sternberg MJE, Cabrera CP, Warren H, Barnes M, Quinton R, de Roux N, Young J, Guiochon-Mantel A, Wehkalampi K, Andre V, Gothilf Y, Cariboni A and Dunkel L (2016). IGSF10 mutations dysregulate gonadotropin‐releasing hormone neuronal migration resulting in delayed puberty. Wiley Embo Molecular Medicine vol. 8, (6) 626-42. 10.15252/emmm.201606250

Tsai SL, Green J, Metherell LA, Curtis F, Fernandez B, Healey A and Curtis J (2016). Primary adrenocortical insufficiency case series: Genetic etiologies more common than expected. Hormone Research in Paediatrics vol. 85, (1) 35-42. 10.1159/000441843

2015

Chan LF, Campbell DC, Novoselova TV, Clark AJL and Metherell LA (2015). Whole-Exome Sequencing in the Differential Diagnosis of Primary Adrenal Insufficiency in Children. Frontiers in Endocrinology vol. 6, 10.3389/fendo.2015.00113

Storr HL, Prasad R, Temple IK, Metherell LA, Savage MO and Walker JM (2015). Heterogeneity of the growth phenotype and birth size in acid-labile subunit (ALS) deficiency. J Endocrinol Invest vol. 38, (4) 407-412. 10.1007/s40618-014-0195-1

Storr HL, Dunkel L, Kowalczyk J, Savage MO and Metherell LA (2015). Genetic characterisation of a cohort of children clinically labelled as GH or IGF1 insensitive: diagnostic value of serum IGF1 and height at presentation. Eur J Endocrinol vol. 172, (2) 151-161. 10.1530/EJE-14-0541

Novoselova TV, Rath SR, Carpenter K, Pachter N, Dickinson JE, Price G, Chan LF, Choong CS and Metherell LA (2015). NNT Pseudoexon Activation as a Novel Mechanism for Disease in Two Siblings With Familial Glucocorticoid Deficiency. Endocrine Society Journal of Clinical Endocrinology & Metabolism vol. 100, (2) E350-E354. 10.1210/jc.2014-3641

2014

Meimaridou E, Kowalczyk J and Metherell LA (2014). Molecular Genetics of Inherited Glucocorticoid Deficiency. Els 10.1002/9780470015902.a0025368

Prasad R, Chan LF, Hughes CR, Kaski JP, Kowalczyk JC, Savage MO, Peters CJ, Nathwani N, Clark AJL, Storr HL and Metherell LA (2014). Thioredoxin Reductase 2 (TXNRD2) mutation associated with familial glucocorticoid deficiency (FGD). J Clin Endocrinol Metab vol. 99, (8) E1556-E1563. 10.1210/jc.2013-3844

Prasad R, Kowalczyk JC, Meimaridou E, Storr HL and Metherell LA (2014). Oxidative stress and adrenocortical insufficiency. J Endocrinol vol. 221, (3) R63-R73. 10.1530/JOE-13-0346

Högler W, Martin DD, Crabtree N, Nightingale P, Tomlinson J, Metherell L, Rosenfeld R, Hwa V, Rose S, Walker J, Shaw N, Barrett T and Frystyk J (2014). IGFALS gene dosage effects on serum IGF-I and glucose metabolism, body composition, bone growth in length and width, and the pharmacokinetics of recombinant human IGF-I administration. J Clin Endocrinol Metab vol. 99, (4) E703-E712. 10.1210/jc.2013-3718

Poukoulidou T, Kowalczyk J, Metherell L, De Schepper J and Maes M (2014). A Novel Homozygous Mutation of the IGFALS Gene in a Female Adolescent: Indirect Evidence for a Contributing Role of the Circulating IGF-I Pool in the Pubertal Growth Spurt. Hormone Research in Paediatrics vol. 81, (6) 422-427. 10.1159/000358329

2013

Habeb AM, Hughes CR, Al-Arabi R, Al-Muhamadi A, Clark AJL and Metherell LA (2013). Familial glucocorticoid deficiency: a diagnostic challenge during acute illness. European Journal of Pediatrics vol. 172, (10) 1407-1410. 10.1007/s00431-013-2044-1

Prasad R, Metherell LA, Clark AJ and Storr HL (2013). Deficiency of ALADIN impairs redox homeostasis in human adrenal cells and inhibits steroidogenesis. Endocrinology vol. 154, (9) 3209-3218. 10.1210/en.2013-1241

Meimaridou E, Prasad R, Kowalczyk JC, Clark AJL, Storr HL and Metherell LA (2013). PP43 Genome sequencing reveals mitochondrial thiol systems are essential for antioxidant defence in human adrenal glands. Free Radical Biology and Medicine vol. 65, 10.1016/j.freeradbiomed.2013.08.052

Meimaridou E, Hughes CR, Kowalczyk J, Guasti L, Chapple JP, King PJ, Chan LF, Clark AJL and Metherell LA (2013). Familial glucocorticoid deficiency: New genes and mechanisms. Mol Cell Endocrinol vol. 371, (1-2) 195-200. 10.1016/j.mce.2012.12.010

Meimaridou E, Hughes CR, Kowalczyk J, Guasti L, Chapple JP, King PJ, Chan LF, Clark AJL and Metherell LA (2013). Familial glucocorticoid deficiency: New genes and mechanisms. Molecular and Cellular Endocrinology vol. 371, (1-2) 195-200. 10.1016/j.mce.2012.12.010

Meimaridou E, Hughes CR, Kowalczyk J, Chan LF, Clark AJL and Metherell LA (2013). ACTH resistance: genes and mechanisms. Endocr Dev vol. 24, 57-66. 10.1159/000342504

Yates R, Katugampola H, Cavlan D, Cogger K, Meimaridou E, Hughes C, Metherell L, Guasti L and King P (2013). Adrenocortical development, maintenance, and disease. Curr Top Dev Biol vol. 106, 239-312. 10.1016/B978-0-12-416021-7.00007-9

2012

Meimaridou E, Kowalczyk J, Guasti L, Hughes CR, Wagner F, Frommolt P, Nürnberg P, Mann NP, Banerjee R, Saka HN, Chapple JP, King PJ, Clark AJL and Metherell LA (2012). Mutations in NNT encoding nicotinamide nucleotide transhydrogenase cause familial glucocorticoid deficiency. Nat Genet vol. 44, (7) 740-742. 10.1038/ng.2299

Turan S, Hughes C, Atay Z, Guran T, Haliloglu B, Clark AJL, Bereket A and Metherell LA (2012). An atypical case of familial glucocorticoid deficiency without pigmentation caused by coexistent homozygous mutations in MC2R (T152K) and MC1R (R160W). J Clin Endocrinol Metab vol. 97, (5) E771-E774. 10.1210/jc.2011-2414

Hughes CR, Guasti L, Meimaridou E, Chuang C-H, Schimenti JC, King PJ, Costigan C, Clark AJL and Metherell LA (2012). MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans. Journal of Clinical Investigation vol. 122, (3) 814-820. 10.1172/JCI60224

2011

Jain V, Metherell LA, David A, Sharma R, Sharma PK, Clark AJL and Chan LF (2011). Neonatal presentation of familial glucocorticoid deficiency resulting from a novel splice mutation in the melanocortin 2 receptor accessory protein. Eur J Endocrinol vol. 165, (6) 987-991. 10.1530/EJE-11-0581

McEachern R, Drouin J, Metherell L, Huot C, Van Vliet G and Deal C (2011). Severe cortisol deficiency associated with reversible growth hormone deficiency in two infants: what is the link? J Clin Endocrinol Metab vol. 96, (9) 2670-2674. 10.1210/jc.2011-0129

David A, Hwa V, Metherell LA, Netchine I, Camacho-Hübner C, Clark AJL, Rosenfeld RG and Savage MO (2011). Evidence for a continuum of genetic, phenotypic, and biochemical abnormalities in children with growth hormone insensitivity. Endocr Rev vol. 32, (4) 472-497. 10.1210/er.2010-0023

Chan LF, Metherell LA and Clark AJL (2011). Effects of melanocortins on adrenal gland physiology. Eur J Pharmacol vol. 660, (1) 171-180. 10.1016/j.ejphar.2010.11.041

Savage MO, Hwa V, David A, Rosenfeld RG and Metherell LA (2011). Genetic Defects in the Growth Hormone-IGF-I Axis Causing Growth Hormone Insensitivity and Impaired Linear Growth. Front Endocrinol (Lausanne) vol. 2, 10.3389/fendo.2011.00095

2010

Hughes CR, Chung TT, Habeb AM, Kelestimur F, Clark AJL and Metherell LA (2010). Missense mutations in the melanocortin 2 receptor accessory protein that lead to late onset familial glucocorticoid deficiency type 2. J Clin Endocrinol Metab vol. 95, (7) 3497-3501. 10.1210/jc.2009-2731

David A, Srirangalingam U, Metherell LA, Khoo B and Clark AJL (2010). Repair of aberrant splicing in growth hormone receptor by antisense oligonucleotides targeting the splice sites of a pseudoexon. J Clin Endocrinol Metab vol. 95, (7) 3542-3546. 10.1210/jc.2009-1968

Moyes VJ, Walker DM, Owusu-Antwi S, Maher KT, Metherell L, Akker SA, Monson JP, Clark AJL and Drake WM (2010). d3-GHR genotype does not explain heterogeneity in GH responsiveness in hypopituitary adults. Clin Endocrinol (Oxf) vol. 72, (6) 807-813. 10.1111/j.1365-2265.2009.03768.x

David A, Srirangalingam U, Metherell LA, Khoo B and Clark AJL (2010). Repair of Aberrant Splicing in Growth Hormone Receptor by Antisense Oligonucleotides Targeting the Splice Sites of a Pseudoexon. Endocrinology vol. 24, (6) 1305-1305. 10.1210/mend.24.6.9994

Hughes C, Chung TT, Clark AJ and Metherell L (2010). FUNCTIONAL CHARACTERISATION OF A MISSENSE MUTATION OF MRAP LEADING TO FAMILIAL GLUCOCORTICOID DEFICIENCY. Irish J Med Sci vol. 179, S263-S263.

Chung T-TLL, Chan LF, Metherell LA and Clark AJL (2010). Phenotypic characteristics of familial glucocorticoid deficiency (FGD) type 1 and 2. Clin Endocrinol (Oxf) vol. 72, (5) 589-594. 10.1111/j.1365-2265.2009.03663.x

Dias RP, Chan LF, Metherell LA, Pearce SHS and Clark AJL (2010). Isolated Addison's disease is unlikely to be caused by mutations in MC2R, MRAP or STAR, three genes responsible for familial glucocorticoid deficiency. Eur J Endocrinol vol. 162, (2) 357-359. 10.1530/EJE-09-0720

David A, Miraki-Moud F, Shaw NJ, Savage MO, Clark AJL and Metherell LA (2010). Identification and characterisation of a novel GHR defect disrupting the polypyrimidine tract and resulting in GH insensitivity. Eur J Endocrinol vol. 162, (1) 37-42. 10.1530/EJE-09-0583

David A, Rose SJ, Miraki-Moud F, Metherell LA, Savage MO, Clark AJL and Camacho-Hübner C (2010). Acid-labile subunit deficiency and growth failure: description of two novel cases. Horm Res Paediatr vol. 73, (5) 328-334. 10.1159/000308164

Storr HL, Metherell LA, Dias R, Savage MO, Rasmussen AK, Clark AJL and Main KM (2010). Familial Isolated Primary Pigmented Nodular Adrenocortical Disease Associated with a Novel Low Penetrance PRKAR1A Gene Splice Site Mutation. Horm Res Paediat vol. 73, (2) 115-119. 10.1159/000277629

Storr HL, Metherell LA, Dias R, Savage MO, Rasmussen AK, Clark AJL and Main KM (2010). Familial isolated primary pigmented nodular adrenocortical disease associated with a novel low penetrance PRKAR1A gene splice site mutation. Horm Res Paediatr vol. 73, (2) 115-119. 10.1159/000277629

2009

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 and Clark AJL (2009). Nonclassic lipoid congenital adrenal hyperplasia masquerading as familial glucocorticoid deficiency. J Clin Endocrinol Metab vol. 94, (10) 3865-3871. 10.1210/jc.2009-0467

(2009). Homozygous nonsense and frameshift mutations of the ACTH receptor in children with familial glucocorticoid deficiency (FGD) are not associated with long-term mineralocorticoid deficiency. Clin Endocrinol (Oxf) vol. 71, (2) 171-175. 10.1111/j.1365-2265.2008.03511.x

Milward A, Metherell L, Maamra M, Barahona MJ, Wilkinson IR, Camacho-Hübner C, Savage MO, Bidlingmaier CM, Clark AJL, Ross RJM and Webb SM (2009). Growth hormone (GH) insensitivity syndrome due to a GH receptor truncated after box1, resulting in isolated failure of STAT 5 signal transduction (Journal of Clinical Endocrinology and Metabolism (2004) 89 (1259-1266)). Journal of Clinical Endocrinology and Metabolism vol. 94, (7)

Milward A, Metherell L, Maamra M, Barahona MJ, Wilkinson IR, Camacho-Huebner C, Savage MO, Bidlingmaier CM, Clark AJL, Ross RJM and Webb SM (2009). Growth Hormone (GH) Insensitivity Syndrome due to a GH Receptor Truncated after Box1, Resulting in Isolated Failure of STAT 5 Signal Transduction (vol 89, pg 1259, 2004). Journal of Clinical Endocrinology & Metabolism vol. 94, (7) 2674-2674.

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. Proc Natl Acad Sci U S A vol. 106, (15) 6146-6151. 10.1073/pnas.0809918106

Chan LF, Chung T-T, Massoud AF, Metherell LA and Clark AJL (2009). Functional consequence of a novel Y129C mutation in a patient with two contradictory melanocortin-2-receptor mutations. Eur J Endocrinol vol. 160, (4) 705-710. 10.1530/EJE-08-0636

Clark AJL, Chan LF, Chung T-T and Metherell LA (2009). The genetics of familial glucocorticoid deficiency. Best Pract Res Clin Endocrinol Metab vol. 23, (2) 159-165. 10.1016/j.beem.2008.09.006

Cooray SN, Chan L, Webb TR, Metherell L and Clark AJL (2009). Accessory proteins are vital for the functional expression of certain G protein-coupled receptors. Mol Cell Endocrinol vol. 300, (1-2) 17-24. 10.1016/j.mce.2008.10.004

Savage MO, David A, Camacho-Hubner C, Metherell LA and Clark AJL (2009). Phenotypic aspects of growth hormone- and IGF-I-resistant syndromes. Endocr Dev vol. 14, 143-150. 10.1159/000207483

Metherell LA, Chung TT, Chan LF and Clark AJL (2009). Genotype:phenotype relationships in familial glucocorticoid deficiency types 1 and 2. Horm Res vol. 72, 211-211.

Chan LF, David A, Jain V, Clark AJL and Metherell LA (2009). A novel splice mutation (IVSds3+3insTA) in the melanocortin 2 receptor accessory protein that leads to skipping of exon 3. Horm Res vol. 72, 70-70.

Hughes CR, Chung TT, Habeb AM, Clark AJ and Metherell LA (2009). Functional characterisation of a missense mutation (p.Y59D) of MRAP which leads to familial glucocorticoid deficiency type 2. Horm Res vol. 72, 42-42.

2008

Chung TT, Webb TR, Chan LF, Cooray SN, Metherell LA, King PJ, Chapple JP and Clark AJL (2008). The majority of adrenocorticotropin receptor (melanocortin 2 receptor) mutations found in familial glucocorticoid deficiency type 1 lead to defective trafficking of the receptor to the cell surface. J Clin Endocrinol Metab vol. 93, (12) 4948-4954. 10.1210/jc.2008-1744

Chan LF, Clark AJL and Metherell LA (2008). Familial glucocorticoid deficiency: advances in the molecular understanding of ACTH action. Horm Res vol. 69, (2) 75-82. 10.1159/000111810

Cooray SN, Chan L, Metherell L, Storr H and Clark AJL (2008). Adrenocorticotropin resistance syndromes. Endocr Dev vol. 13, 99-116. 10.1159/000134828

David A, Rose S, Miraki-Moud F, Metherell L, Clark A, Savage M and Camacho-Hubner C (2008). Acid-labile subunit gene mutations: Clinical, biochemical and molecular study in two unrelated families. Horm Res vol. 70, 31-31.

Chan L, Chung TT, Massoud A, Metherell L and Clark A (2008). Functional consequence of two opposing MC2R mutations in a child with severe FGD phenotype. Horm Res vol. 70, 23-23.

2007

Vallette-Kasic S, Couture C, Balsalobre A, Gauthier Y, Metherell L, Dattani M and Drouin J (2007). The TPIT gene mutation M86R associated with isolated adrenocorticotropin deficiency interferes with protein: Protein interactions. J Clin Endocr Metab vol. 92, (10) 3991-3999. 10.1210/jc.2007-0284

Rumié H, Metherell LA, Clark AJL, Beauloye V and Maes M (2007). Clinical and biological phenotype of a patient with familial glucocorticoid deficiency type 2 caused by a mutation of melanocortin 2 receptor accessory protein. Eur J Endocrinol vol. 157, (4) 539-542. 10.1530/EJE-07-0242

Savage MO, Camacho-Hübner C, David A, Metherell LA, Hwa V, Rosenfeld RG and Clark AJL (2007). Idiopathic short stature: will genetics influence the choice between GH and IGF-I therapy? Eur J Endocrinol vol. 157 Suppl 1, S33-S37. 10.1530/EJE-07-0292

Keegan CE, Hutz JE, Krause AS, Koehler K, Metherell LA, Boikos S, Stergiopoulos S, Clark AJL, Stratakis CA, Huebner A and Hammer GD (2007). Novel polymorphisms and lack of mutations in the ACD gene in patients with ACTH resistance syndromes. Clin Endocrinol vol. 67, (2) 168-174. 10.1111/j.1365-2265.2007.02855.x

David A, Camacho-Hübner C, Bhangoo A, Rose SJ, Miraki-Moud F, Akker SA, Butler GE, Ten S, Clayton PE, Clark AJL, Savage MO and 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 vol. 92, (2) 655-659. 10.1210/jc.2006-1527

Lin L, Hindmarsh PC, Metherell LA, Alzyoud M, Al-Ali M, Brain CE, Clark AJL, Dattani MT and Achermann JC (2007). Severe loss-of-function mutations in the adrenocorticotropin receptor (ACTHR, MC2R) can be found in patients diagnosed with salt-losing adrenal hypoplasia. Clin Endocrinol (Oxf) vol. 66, (2) 205-210. 10.1111/j.1365-2265.2006.02709.x

Hwa V, Camacho-Hübner C, Little BM, David A, Metherell LA, El-Khatib N, Savage MO and Rosenfeld RG (2007). Growth hormone insensitivity and severe short stature in siblings: a novel mutation at the exon 13-intron 13 junction of the STAT5b gene. Horm Res vol. 68, (5) 218-224. 10.1159/000101334

2006

Metherell LA, Chan LF and Clark AJL (2006). The genetics of ACTH resistance syndromes. Best Pract Res Clin Endocrinol Metab vol. 20, (4) 547-560. 10.1016/j.beem.2006.09.002

Savage MO, Attie KM, David A, Metherell LA, Clark AJL and Camacho-Hübner C (2006). Endocrine assessment, molecular characterization and treatment of growth hormone insensitivity disorders. Nat Clin Pract Endocrinol Metab vol. 2, (7) 395-407. 10.1038/ncpendmet0195

Clark AJL and Metherell LA (2006). Mechanisms of disease: the adrenocorticotropin receptor and disease. Nat Clin Pract Endocrinol Metab vol. 2, (5) 282-290. 10.1038/ncpendmet0165

Maamra M, Milward A, Esfahani HZ, Abbott LP, Metherell LA, Savage MO, Clark AJL and Ross RJM (2006). A 36 residues insertion in the dimerization domain of the growth hormone receptor results in defective trafficking rather than impaired signaling. J Endocrinol vol. 188, (2) 251-261. 10.1677/joe.1.06252

2005

Clark AJL, Metherell LA, Cheetham ME and Huebner A (2005). Inherited ACTH insensitivity illuminates the mechanisms of ACTH action. Trends Endocrinol Metab vol. 16, (10) 451-457. 10.1016/j.tem.2005.10.006

David A, Metherell LA, Clark AJL, Camacho-Hubner C and Savage MO (2005). Diagnostic and therapeutic advances in growth hormone insensitivity. Endocrin Metab Clin vol. 34, (3) 581-+. 10.1016/j.ecl.2005.04.009

Hui HNT, Metherell LA, Ng KL, Savage MO, Camacho-Hubner C and Clark AJL (2005). Novel growth hormone receptor mutation in a Chinese patient with Laron syndrome. J Pediatr Endocr Met vol. 18, (2) 209-213. 10.1515/jpem.2005.18.2.209

Metherell LA, Chapple JP, Cooray S, David A, Becker C, Rüschendorf F, Naville D, Begeot M, Khoo B, Nürnberg P, Huebner A, Cheetham ME and Clark AJL (2005). Mutations in MRAP, encoding a new interacting partner of the ACTH receptor, cause familial glucocorticoid deficiency type 2. Nat Genet vol. 37, (2) 166-170. 10.1038/ng1501

CLARK AJL, Metherell LA, Huebner A, Begeot M and Naville D (2005). Genetics of ACTH insensitivity syndromes. Annals of Endocrinology vol. 66, 247-249. 10.1016/S0003-4266(05)81757-3

2004

Metherell LA, Savage MO, Dattani M, Walker J, Clayton PE, Farooqi IS and Clark AJL (2004). TPIT mutations are associated with early-onset, but not late-onset isolated ACTH deficiency. Eur J Endocrinol vol. 151, (4) 463-465. 10.1530/eje.0.1510463

Milward A, Metherell L, Maamra M, Barahona MJ, Wilkinson IR, Camacho-Hubner C, Savage MO, Bidlingmaier CM, Clark AJL, Ross RJM and 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 Endocr Metab vol. 89, (3) 1259-1266. 10.1210/jc.2003-031418

2003

Kola B, Korbonits M, Diaz-Cano S, Kaltsas G, Morris DG, Jordan S, Metherell L, Powell M, Czirják S, Arnaldi G, Bustin S, Boscaro M, Mantero F and Grossman AB (2003). Reduced expression of the growth hormone and type 1 insulin-like growth factor receptors in human somatotroph tumours and an analysis of possible mutations of the growth hormone receptor. Clin Endocrinol (Oxf) vol. 59, (3) 328-338. 10.1046/j.1365-2265.2003.01851.x

Swords F, Metherell L, Arola J and Clark A (2003). No Evidence for a Role for Mutations in the cAMP-Dependent Protein Kinase a Regulatory Subunit in Hyperfunctioning Adrenocortical Adenomas. Clinical Science vol. 104, (s49) 20p-20p. 10.1042/cs104020p

2002

Bjarnason R, Banerjee K, Rose SJ, Rosberg S, Metherell L, Clark AJL, Albertsson-Wikland K and Savage MO (2002). Spontaneous growth hormone secretory characteristics in children with partial growth hormone insensitivity. Clin Endocrinol vol. 57, (3) 357-361. 10.1046/j.1365-2265.2002.01607.x

2001

Metherell LA, Akker SA, Munroe PB, Rose SJ, Caulfield M, Savage MO, Chew SL and Clark AJ (2001). Pseudoexon activation as a novel mechanism for disease resulting in atypical growth-hormone insensitivity. Am J Hum Genet vol. 69, (3) 641-646. 10.1086/323266

Edwards KJ, Metherell LA, Yates M and Saunders NA (2001). Detection of rpoB mutations in Mycobacterium tuberculosis by biprobe analysis. J Clin Microbiol vol. 39, (9) 3350-3352. 10.1128/JCM.39.9.3350-3352.2001

Clark AJ, Metherell L, Swords FM and Elias LL (2001). The molecular pathogenesis of ACTH insensitivity syndromes. Ann Endocrinol (Paris) vol. 62, (2) 207-211.

Clark AJ, Metherell L, Swords FM and Elias LL (2001). The molecular pathogenesis of ACTH insensitivity syndromes. Annales D'Endocrinologie vol. 62, (2) 207-211.

2000

Elias LLK, Huebner A, Metherell LA, Canas A, Warne GL, Manca Bitti ML, Cianfarani S, Clayton PE, Savage MO and Clark AJL (2000). Tall stature in familial glucocorticoid deficiency. Clinical Endocrinology vol. 53, (4) 423-430. 10.1046/j.1365-2265.2000.01122.x

1999

Metherell LA, Logan JMJ and Stanley J (1999). PCR-enzyme-linked immunosorbent assay for detection and identification of Campylobacter species: Application to isolates and stool samples. Journal of Clinical Microbiology vol. 37, (2) 433-435. 10.1128/jcm.37.2.433-435.1999

Arnold C, Metherell L, Clewley JP and Stanley J (1999). Predictive modelling of fluorescent AFLP: A new approach to the molecular epidemiology of E. coli. Research in Microbiology vol. 150, (1) 33-44. 10.1016/S0923-2508(99)80044-8

Clode FE, Metherell LA, Pitt TL, Wilsher ML, Kolbe J, Morris AJ, Welch DF and Vandamme PAR (1999). Nosocomial acquisition of Burkholderia gladioli in patients with cystic fibrosis (multiple letters). American Journal of Respiratory and Critical Care Medicine vol. 160, (1) 374-375. 10.1164/ajrccm.160.1.16011

Arnold C, Metherell L, Willshaw G, Maggs A and Stanley J (1999). Predictive fluorescent amplified-fragment length polymorphism analysis of Escherichia coli: High-resolution typing method with phylogenetic significance. Journal of Clinical Microbiology vol. 37, (5) 1274-1279. 10.1128/jcm.37.5.1274-1279.1999

1997

Metherell LA, Hurst C and Bruce IJ (1997). Rapid, sensitive, microbial detection by gene amplification using restriction endonuclease target sequences. Molecular and Cellular Probes vol. 11, (4) 297-308. 10.1006/mcpr.1997.0120

Saunders NA, Metherell L and Patel S (1997). Investigation of an outbreak of multidrug resistant tuberculosis among renal patients using rpo B gene sequencing and IS6110 inverse PCR. Journal of Infection vol. 35, (2) 129-133. 10.1016/S0163-4453(97)91512-7

Saunders NA, Hallas G, Gaworzewska ET, Metherell L, Efstratiou A, Hookey JV and George RC (1997). PCR-enzyme-linked immunosorbent assay and sequencing as an alternative to serology for M-antigen typing of Streptococcus pyogenes. Journal of Clinical Microbiology vol. 35, (10) 2689-2691. 10.1128/jcm.35.10.2689-2691.1997

Grants

The role of MYLK3 in cardiac signalling and development
Metherell L and Williams J
£632,000 British Heart Foundation (01-01-2022 - 31-12-2024)

Interrogating the role of SGPL1 in adrenal/gonadal development and acute steroidogenesis
Metherell L, Prasad R and Kwong R
£378,305 Medical Research Council (04-03-2022 - 03-03-2024)

Improved genetic diagnosis of primary adrenal insufficiency
Storr HL, Metherell LA and Chan L
£500,199 Barts Charity (01-08-2018 - 31-07-2022)

The role of myosin light chain kinase 3 (Mylk3) in dilated cardiomyopathy
Williams J and Metherell L
£114,000 Barts Charity (01-04-2021 - 01-04-2022)

Investigating the role of the sphingolipid pathway in a novel syndromic form of primary adrenal insufficiency
Metherell LA
£318,860 Barts Charity (01-04-2020 - 01-01-2020)

Antioxidant defence in adrenocortical cells
Metherell LA
£392,467 Medical Research Council (31-03-2013 - 30-03-2016)

Summary