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

Genetic diagnosis: We have developed new diagnostics for genetic disorders associated with elevated thyroid hormones and an NHS Gene Panel is now available for use by physicians in the UK (R182).

TRIAC II trial.  Can treatment with TRIAC (thyroid hormone analogue) alter neurodevelopmental outcome in infants with defective thyroid hormone transporter (MCT8)?

I direct the Cambridge Clinical Research Centre, comprising several units and clinical research facilities within which virtually all experimental medicine and translational research on the Biomedical campus, is conducted.

It is a privilege to direct the PhD for Health Professionals programme which trains health professionals researchers and future research leaders.

 

Selected Publications

Romartinez-Alonso B*, Agostini M*, Jones H, McLellan J,  Sood D, Tomkinson N, Marelli F, Gentile I,  Visser WE, Schoenmakers E, Fairall F, Privalsky M, Moran C, Persani  L, Chatterjee K^†,  John Schwabe J^†. Structure-guided approach to relieving transcriptional repression in Resistance to Thyroid Hormone alpha. Molecular and Cellular Biology (2022) (*coequal first authors;^†joint senior authors). doi.org/10.1128/MCB.00363-21

Munro APS, Jalani L, Cornelius, V, Aley PK, Babbage G, Baxter D,  Bula M,  Cathie K, Chatterjee K, Dodd K, Enever Y, Gokani K, Goodman A, Green CA, Harndahl L, Haughney J,  Hicks A,  van der Klaauw A, Kwok J, Libri V, Llewelyn M, McGregor AC,  Minassian A, Moore P, Mughal M, Mujadidi YF, Murira J, Osanlou O, Osanlou R, Owens DR, Pacurar M, Palfreeman A, Pan D, Rampling R, Regan K,  Saich S,  Sakeld J, Saralaya D, Sharma S, Sheridan R, Sturdy A, Thomson EC, Todd S,  Twelves C,  Read R, Charlton S, Hallis B, Ramsay M, Andrews N, Nguyen-Van-Tam JS,  Snape MD, Liu X, Faust SN and the COV-BOOST study group. Safety and immunogenicity of seven COVID-19 vaccines as a third dose (booster) following two doses of ChAdOx1-nCov19 (AZD1222) or BNT162b2: A blinded, randomised controlled trial (COV-BOOST). Lancet (2021).  doi.org/10.1016/S0140-6736(21)02717-3

Torok ME, Underwood BR, Toshner M, Waddington C, Sidhom E, Sharrocks K, Bousfield R, Summers C, Saunders C, McIntyre Z, Morris H, Piper J, Calderon G, Dennis S, Assari T, Marguerie de Rotrou A, Shaw A, Bradley J, O’Brien J, Rintoul RC, Smith I, Bullmore E, Chatterjee K and on behalf of the Cambridge COVID vaccine trial team. Challenges and opportunities for conducting a vaccine trial during the COVID-19 pandemic in the United Kingdom. Clinical Trials (2021) 18: 615-621. PMID:34154428; PMCID:PMC8479147

Moran C, McEniery CM, Schoenmakers N, Mitchell C, Sleigh A, Watson L, Lyons G, Burling K, Barker P, Chatterjee K. Dyslipidemia, insulin resistance, ectopic lipid accumulation and vascular function in Resistance to Thyroid Hormone β. J. Clin. Endocrinol. Metab. (2021) 106: e2005-e2014. PMID:33524107; PMCID:PMC8063262

Di Cicco E*, Moran C*, Visser WE, Nappi A, Schoenmakers E, Todd P, Lyons G, Dattani M, Ambrosio R, Parisi S, Salvatore D, Chatterjee VK^†, Dentice M^†. Germline mutations in the thyroid hormone receptor alpha gene predispose to cutaneous tags and melanocytic nevi. Thyroid (2021) 31: 1114-1126 (*coequal first authors;^†joint senior authors). PMID:33509032; PMCID:PMC8290313

Moran C, Seger C, Taylor K, Oddy S, Burling K, Rajanayagam O, Fairall L, McGowan A, Lyons G, Halsall D, Gurnell M, Schwabe J, Chatterjee K*, Strey C*. Hyperthyroxinemia and Hypercortisolemia due to Familial Dysalbuminemia. Thyroid (2020) 30: 1681-1684 (*co-equal senior authors). PMID:32669045; PMCID:PMC7692891

Mlcochova P, Collier D, Ritchie A, Assennato SM, Hosmillo M, Goel N, Mend B, Chatterjee K, Mendoza V, Temperton N, Kiss L, James LC, Ciazynska KA, Xiong X, Briggs JAG, Nathan JA, Mescia F, Bergamaschi L, Zhang H, Barmpounakis P, Demeris N, Skells R, Lyons PA, Bradley J, Baker S, Allain JP, Smith KGC, Bousfield R, Wilson M, Sparkes D, Amoroso G, Gkrania-Klotsas E, Hardwick S, Boyle A, Goodfellow I, Gupta RK. Combined point-of-care nucleic acid and antibody testing for SARS-COV2 following emergence of D614G spike variant. Cell Rep. Med. (2020) 1: 100099. PMID:32905045; PMCID:PMC7462534

Warde KM, Schoenmakers E, Ribes Martinez E, Lim YJ, Leonard M, Lawless SJ, O’Shea P, Chatterjee K, Gurnell M, Hantel C, Dennedy MC. Liver X receptor inhibition potentiates mitotane-induced adrenotoxicity in adrenocortical cancer. Endocr. Relat. Cancer (2020) 27: 361-373. PMID:32276262; Europe PMC

Groeneweg S, van Geest FS, Abacı A, Alcantud A, Ambegaonkar GP, Armour CM, Bakhtiani P, Barca D,Bertini ES, van Beynum IM, Brunetti-Pierri N, Bugiani M, Cappa M, Cappuccio G, Castellotti B,Castiglioni C, Chatterjee K, de Coo IFM, Coutant R, Craiu D, Crock P, DeGoede C, Demir K, Dica A,Dimitri P, Dolcetta-Capuzzo A, Dremmen MHG, Dubey R, Enderli A, Fairchild J, Gallichan J, George B,Gevers EF, Hackenberg A, Halasz Z, Heinrich B, Huynh T, Kłosowska A, van der Knaap MS, van der Knoop MM,Konrad D, Koolen DA, Krude H, Lawson-Yuen A, Lebl J, Linder-Lucht M, Lorea CF, Lourenco CM,Lunsing RJ, Lyons G, Malikova J, Mancilla EE, McGowan A, Mericq V, Lora FM, Moran C, Müller KE,Oliver-Petit I, Paone L, Paul PG, Polak M, Porta F, Poswar FO, Reinauer C, Rozenkova K,Menevse TS, Simm P, Simon A, Singh Y, Spada M, van der Spek J, Stals MAM, Stoupa A,Subramanian GM, Tonduti D, Turan S, den Uil CA, Vanderniet J, van der Walt A, Wemeau JL, Wierzba J,de Wit MY, Wolf NI, Wurm M, Zibordi F, Zung A, Zwaveling-Soonawala N, Visser WE. Disease characteristics of MCT8 deficiency: an international, retrospective, multicentre study. Lancet Diabetes Endocrinol. (2020) 8: 594-605. PMID:32559475; Europe PMC

Khoo S, Lyons G, McGowan A, Gurnell M, Oddy S, Visser WE, van den Berg S, Halsall D, Taylor K, Chatterjee K*, Moran C. Familial dysalbuminaemic hyperthyroxinaemia interferes with current free thyroid hormone immunoassay methods. Eur. J. Endocrinol. (2020) 182: 533-538 (*senior author). PMID:32213658; PMCID:PMC7222281

Schoenmakers E, Chatterjee K. Human disorders affecting the selenocysteine incorporation pathway cause systemic selenoprotein deficiency. Antioxid. Redox Signal. (2020) 33: 481-497. PMID:32295391; PMCID:PMC7409586

Uter J, Heldmann M, Rogge B, Obst M, Steinhardt J, Brabant G, Moran C, Chatterjee K, Munte T. Patients with mutations of the thyroid hormone beta receptor show an ADHD-like phenotype for performance monitoring: an electrophysiological study. Neuroimage Clin. (2020) 26: 102250. PMID:32217468; PMCID:PMC7109456

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) 7: 695-706. PMID:31377265; Europe PMC

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) 116: 22754-22763. PMID:31628250; PMCID:PMC6842615

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) 67: 1086-1092 (*coequal first authors;^†joint senior authors). PMID:29622583; PMCID:PMC5967605

Achermann JC, Schwabe J, Fairall L, Chatterjee K. Genetic disorders of Nuclear Receptors. J. Clin. Invest. (2017) 127: 1181-1192. PMID: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. Nat. Genet. (2016) 48: 1570-1575 (*coequal first authors). PMID: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: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. Lancet Diabetes Endocrinol. (2014) 2: 619-626 (*co-equal first authors). PMID: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 Mutation in the Thyroid Hormone Receptor Alpha Gene. N. Engl. J. Med. (2012) 366: 243-249 (*coequal first authors). PMID:22168587; Europe PMC