Our principal research interests are in genetic and molecular endocrinology, with particular emphasis on disorders nuclear hormone synthesis and action. We study several human disorders: Resistance to Thyroid Hormone (RTH), defined broadly as abnormal circulating thyroid hormones with tissue refractoriness to hormone action; and PPARgamma gene defects associated with lipodystrophic insulin resistance. 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 alter physiological processes acting via receptor subtypes in tissues. In a multisystem selenoprotein deficiency disorder including thyroid deiodinase enzymes, we are investigating features (cardiovascular, metabolic, photosensitivity) attributable to elevated ROS and the roles of selenoproteins of unknown function. Finally, we translate our research into technologies (biochemical, genetic) that comprise our national diagnostic laboratory service, develop biomarkers of hormone action and trial therapies (e.g. selective thyromimetics) that are applicable to commoner thyroid dysfunction or metabolic disorders.
Achermann JC, Schwabe J, Fairall L, Chatterjee K. Genetic disorders of Nuclear Receptors J. Clin. Invest. (2017) 127: 1181-1192. doi: 10.1172/JCI88892. PMID number: 28368288
Majithia AR*, Tsuda B*, Agostini M*, Gnanapradeepan K*, Rice R, Peloso G, Patel KA, Zhang X, Broekema MF, Patterson N, Duby M, Sharpe T, Kalkhoven E, Rosen ED, Barroso I, Ellard S, UK Monogenic Diabetes Consortium, Kathiresan S, Myocardial Infarction Genetics Consortium, O’Rahilly S, UK Congenital Lipodystrophy Consortium, Chatterjee K, Florez JC, Mikkelsen T, Savage DB, Altshuler D. Prospective functional classification of all possible missense variants in PPARG. Nature Genetics (2016) 48: 1570-1575. PMID number: 27749844
Schoenmakers E, Carlson B, Agostini M, Moran C, Rajanayagam O, Bockukova E, Tobe R, Peat R, Gevers E, Muntoni F, Guicheney P, Schoenmakers N, Farooqi S, Lyons G, Hatfield D, Chatterjee K. Mutation in human selenocysteine transfer RNA selectively disrupts selenoprotein synthesis. J. Clin. Invest. (2016) 126: 992-996. PMID number: 26854926. PMCID:PMC4767355
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.
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.