Research Interests

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.

Public engagement: Story of a patient with Resistance to Thyroid Hormone alpha identified via 100,000 Genomes Project 

 

Selected Publications

Groeneweg S, Peeters RP, Moran C, Stoupa A, Auriol F, Tonduti D,  Dica A, Paone L, Rozenkova K, Malikova J, van der Walt A, de Coo IFM, McGowan A, Lyons G, Aarsen FK, Barca D, van Beynum IM, van der Knoop MM, Jansen J, Manshande M, Lunsing RJ, Nowak S, den Uil CA, Zillikens MC, Visser FE, Vrijmoeth P, de Wit MCY, Wolf NI, Zandstra A, Ambegaonkar G, Singh Y, de Rijke YB, Medici M, Bertini ES, Depoorter S, Lebl J, Cappa M, De Meirleir L, Krude H, Craiu D, Zibordi F, Oliver-Petit I, Polak M, Chatterjee K, Visser TJ, Visser WE. Effectiveness and safety of Triac in children and adults with MCT8 deficiency: an international, multicentre, single group, open-label, phase 2 trial.  Lancet Diabetes Endocrinol. (2019) http://dx.doi.org/10.1016/S2213-8587(19)30155-X.  PMID number: 31377265

Krieger TG, Moran CM, Frangini A, Visser WE, Schoenmakers E, Muntoni F, Clark C, Gadian D, Chong WK, Kuczynski A, Dattani M, Lyons G, Efthymiadou A, Varga-Khadem F, Simons BD, Chatterjee K, Livesey FJ.  Mutations in thyroid hormone receptor alpha1 cause premature neurogenesis and progenitor cell depletion in human cortical development.  Proc.Natl.Acad.Sci USA (2019) Pii:201908762. http://doi.org/10.1073/pnas.1908762116. PMID:31628250

Agostini M*, Schoenmakers E*, Beig J, Fairall L, Szatmari I, Rajanayagam O, Muskett FW, Adams C, Marais AD, O’Rahilly S, Semple RK, Nagy L, Majithia A, Schwabe JWR, Blom DJ, Murphy R, Chatterjee K^†, Savage DB^†. A Pharmacogenetic Approach to the Treatment of Patients With PPARG Mutations. Diabetes. 2018 Jun;67(6):1086-1092. (*coequal first authors; ^†joint senior authors) PMID Number:29622583.  PMCID: PMC5967605

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. PMCID: PMC5373888

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. (*coequal first authors) PMID number: 27749844. PMCID: PMC5131844

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 number: 24969835. PMCID: PMC5989926

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. N. Engl. J. of Med. (2012) 366:243-249(*coequal first authors). PMID number: 22168587.