MRL Home

Krishna Chatterjee

FMedSci

Professor of Endocrinology

Department of Medicine

Contact

Group members

 

Research Interests and activities

Staff photo

Our principal research interests are in genetic and molecular endocrinology, with particular emphasis on disorders nuclear hormone synthesis and action. We study several human cohorts: Resistance to Thyroid Hormone (RTH), defined broadly as abnormal circulating thyroid hormones with tissue refractoriness to hormone action; and lipodystrophic insulin resistance associated with PPARg gene defects.  Candidate gene and whole exome approaches are used to identify novel genetic aetiologies mediating defective hormone action.  Human phenotypic studies elucidate mechanisms whereby thyroid hormones modulate energy balance (intake, expenditure) or act via receptor subtypes in tissues.  In a multisystem selenoprotein deficiency disorder including thyroid deiodinases, we are investigating features (metabolic, photosensitivity) attributable to elevated ROS and the roles of selenoproteins of unknown function.  Finally, we aim to translate our research into technologies (biochemical, genetic) which enhance our national diagnostic laboratory service and to develop biomarkers of hormone action and therapies (e.g. selective thyromimetics, PPARg modulators) that are application to commoner thyroid dysfunction or metabolic disorders.


Our research is funded by the Wellcome Trust and NIHR Cambridge Biomedical Research Centre.

 

Selected Publications

Moran C*, Agostini M*, Visser WE, Schoenmakers E, Schoenmakers N, Offiah AC, Poole K, Rajanayagam O, Lyons G, Halsall D, Gurnell M, Chrysis D, Eythimiadou A, Buchanan C, Aylwin S and Chatterjee K. Resistance to Thyroid Hormone caused by a mutation in thyroid hormone receptor (TR) alpha1 and TRalpha2: clinical, biochemical and genetic anayses of three related patients (*co-equal first authors). Lancet Diabetes Endocrinol. (2014) 2: 619-626. PMID 24969835.

 

Schoenmakers N*, Moran C*, Campi I, Agostini M, Bacon O, Rajanayagam O, Schwabe J, Bradbury S, Barrett T, Geohegan F, Druce M, Beck-Peccoz P, O'Toole A, Clark P, Bignell M, Lyons G, Halsall D, Gurnell M, Chatterjee VKK. (2014). A novel albumin gene mutation (R222I) in Familial Dysalbuminaemic Hyperthyroxinaemia. Journal of Clinical Endocrinology and Metabolism, doi.org/10.1210/jc.2013-4077 (*coequal first authors). PMID: 24646103.

 

Moran C*, Schoenmakers N*, Agostini M, Schoenmakers E, Offiah A, Kydd A, Kahaly G, Mohr-Kahaly S, Rajanayagam O, Lyons G, Wareham N, Halsall D, Dattani M, Hughes S, Gurnell M, Park S-M, Chatterjee VKK. (2013). An adult female with Resistance to Thyroid Hormone mediated by defective thyroid hormone receptor alpha. Journal of Clinical Endocrinology and Metabolism, 98, 4254-4261. PMID: 23940126.

 

Sun Y*, Bak B*, Schoenmakers N*, van Trostsenburg ASP*, Oostdijk W, Voshol P, Cambridge E, White JK, le Tissier P, Gharavy SNM, Martinez-Barbera JP, Stokvis-Brantsma WH, Vulsma T, Kempers MJ, Persani L, Campi I, Bonomi M, Beck-Peccoz P, Zhu H, Davis TME, Hokken-Koelega ACS, Del Blanco DG, Rangasami JJ, Ruivenkamp CAL, Laros JFJ, Kriek M, Kant SG, Bosch CAJ, Biermasz NR, Appelman-Dijkstra NM, Corssmit EP, Hovens GCJ, Pereira AM, den Dunnen JT, Wade MR, Breuning MH, Hennekam RC, Chatterjee K†, Dattani MT†, Wit JM†, Bernard DJ†. (2012). Loss-of-function mutations in IGSF1 cause a X-linked syndrome of central hypothyroidism and testicular enlargement. Nature Genetics, 44, 1375-1381. PMID: 23143598.

 

Bochukova E*, Schoenmakers N*, Agostini M, Schoenmakers E, Rajanayagam O, Keogh JM, Henning E, Reinemund J, Gevers E, Sarri M, Downes K, Offiah A, Albanese A, Halsall D, Schwabe J, Bain M, Lindley K, Muntoni F, Vargha Khadem F, Dattani M, Farooqi S, Gurnell M, Chatterjee K. (2012). A Dominant Negative Mutation in the Thyroid Hormone Receptor Alpha Gene. New England Journal of Medicine, 366:243-249. PMID: 22168587.

 

Schoenmakers E, Agostini M, Mitchell C, Schoenmakers N,  Papp L, Rajanayagam O, Padidela R, Ceron-Gutierrez L, Doffinger R, Prevosto C, Luan J, Montano S, Lu J, Castanet M, Clemons N, Groeneveld M, Castets P, Karbasschi M, Aitken S, Dixon A, Williams J, Campi I, Blount M, Burton H, Muntoni F, O'Donovan D, Dean A, Warren A, Brierley C, Baguley D, Guicheney P, Fitzgerald R, Coles A, Gaston H, Todd P, Holmgren A, Khanna KK, Cooke M, Semple R, Halsall D, Wareham N, Schwabe J, Grasso L, Beck-Peccoz P, Ogunko A, Dattani M, Gurnell M, Chatterjee K. (2010). Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans. Journal of Clinical Investigation 120(12):4220-35). PMID: 21084748. PMCID: PMC2993594.

 

Lopez M, Varela L, Vazquez MJ, Rodriguez-Cuenca S, Gonzalez CR, Velagapudi VR, Morgan DA, Schoenmakers E, Agassandian K, Lage R, de Morentin PB, Tovar S, Nogueiras R, Carling D, Lelliott C, Gallego R, Oresic M, Chatterjee K, Saha AK, Rahmoundi K, Dieguez C, Vidal-Puig A. (2010). Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nature Medicine, 16(9):1001-8.  PMID: 20802499. PMCID: PMC2935934.

 

Mitchell CS, Savage DB, Dufour S, Schoenmakers N, Murgatroyd P, Befroy D, Halsall D, Northcott S, Raymond-Barker P, Curran S, Henning E, Keogh J, Owen P, Lazarus J, Rothman DL, Farooqi IS, Shulman GI, Chatterjee K, Petersen KF. (2010). Resistance to thyroid hormone is associated with raised energy expenditure, muscle mitochondrial uncoupling and hyperphagia. J Clin Invest, 120(4):1345-54. PMID: 20237409.

 

Agostini M, Schoenmakers E, Mitchell CS, Szatmari I, Savage DB, Smith AG, Rajanayagam O, Semple RK, Luan J, Bath L, Zalin AN, Labib M, Kumar S, Simpson H, Blom D, Marais AD, Schwabe JWR, Barroso I, Trembath R, Wareham NJ, Nagy L, Gurnell M, O'Rahilly S, & Chatterjee VKK. (2006). Non-DNA binding, dominant-negative, human PPARγ mutations cause lipodystrophic insulin resistance. Cell Metab, 4(4):303-311. PMID: 17011503. PMCID: PMC1821092.

 

Kallenberger BC, Love JD, Chatterjee VKK, Schwabe JWR. (2003). A dynamic mechanism of nuclear receptor activation and its perturbation in a human disease. Nat Struct Biol, 10(2):136-40. PMID: 12536206.

 

Tinnikov A, Nordstrom K, Thoren P, Kindblom JM, Malin S, Rozell B, Adams M, 
Rajanayagam O, Forrest D, Pettersson S, Ohlsson C, Chatterjee K, Vennstrom B. (2002). Retardation of post-natal development caused by a negatively acting thyroid hormone receptor a1. EMBO J, 21(19):5079-87. PMID: 12356724. PMCID: PMC129045.

 

Barroso I, Gurnell M, Crowley VEF, Agostini M, Schwabe JW, Soos MA, Maslen GLl, Williams TDM, Lewis H, Schafer AJ, Chatterjee VKK & O’Rahilly S. (1999). Dominant negative mutations in human PPARg are associated with severe insulin resistance, diabetes mellitus and hypertension. Nature, 402(6764):880-3. PMID: 10622252.