Name:   V Krishna K CHATTERJEE

Present appointment: (Job title, department, and organisation.)

Director of Research & Emeritus Professor of Endocrinology, Cambridge University Hospitals NHS Foundation Trust

Address: (Full work address.)

University of Cambridge Metabolic Research Laboratories

Level 4 Wellcome-MRC Institute of Metabolic Science

Box 289 Addenbrooke’s Hospital, Cambridge, CB2 0QQ

Email address:

kkc1@medschl.cam.ac.uk

Qualifications:

1979: B.A. Pathology, Class 1, University of Cambridge

1982: B.M.B.Ch., University of Oxford Medical School

1985: M.R.C.P., Royal College of Physicians (UK)

1996: F.R.C.P.

Professional registration: (Name of body, registration number and date of registration.)

GMC: 2597722. Date of registration: 01 Aug 1983

Previous and other appointments: (Include previous appointments in the last 5 years and other current appointments.)

1994 - ongoing: Honorary Consultant Physician, Addenbrooke’s NHS Trust, Cambridge

2002 - ongoing: Director, NIHR Cambridge Clinical Research Centre

2007 - 2017:      Deputy Scientific Director, NIHR Cambridge Biomedical Research Centre

2007 - ongoing: Deputy Director and then Director, Wellcome PhD Programme for Clinicians

2003 - ongoing: Director, Supraregional Assay Service, Addenbrooke's Hospital, Cambridge

1998 - 2018:      Professor of Endocrinology, Dept of Medicine, University of Cambridge

Awards and Honours:

2025: Gerald Aurbach award for Outstanding Translational Research, Endocrine Society

2025: European Hormone Medal, European Society of Endocrinology

2023: CBE for services to people with endocrine disorders

2018: Dale Medal, Society for Endocrinology

2017: Fellow of the Royal Society

2017: President, British Thyroid Association

2016: Dr Archibald Pitcairne Lecture, Royal College of Physicians, Edinburgh

2015: Emeritus Senior Investigator, National Institute for Health Research

2015: Merck-Serono Prize, European Thyroid Association

2014: Pitt-Rivers Medal Lecture, British Endocrine Society

2013: European Thyroid Journal Opening Plenary Lecture, European Thyroid Association

2011: Sidney Ingbar Visiting Lecturer, Harvard Medical School

2009: Senior Investigator, National Institute for Health Research

2006: Medal of the Society for Endocrinology, UK

2003: Eli Lilly HypoCCS Prize Lecture

2001: Clinical Endocrinology Trust Prize Lecturer, British Endocrine Society

Invited Lectures:

2024: Invited Speaker, American Thyroid Association, USA

2023: Invited Speaker, Grand Rounds, Johns Hopkins, USA

2022: Invited Speaker, EMBO Nuclear Receptor workshop, Malta

2021: Plenary Speaker, International Congress of Endocrinology

2019: MacIntyre Award for Endocrinology, William Harvey Research Institute, St

          Bartholomew’s & Royal London Hospitals

2017: Invited Speaker, FEBS Nuclear Receptors and Disease, Spetses

2016: Plenary Speaker, American Thyroid Association

2014: Plenary Lecture, Italian Thyroid Association

2013: Plenary Lecture, Societe d’Endocrinologie, France

2012: Plenary Lecture, American Thyroid Association, USA

2011: Invited Speaker, EMBO Nuclear Receptor Meeting, Barcelona

2010: Invited Speaker, Dutch Endocrine Society

2009: Invited Speaker, EMBO Nuclear receptor meeting, Croatia

2008: Invited Speaker, International Congress of Endocrinology, Rio de Janeiro, Brazil

2007: Invited Speaker, NIH Workshop on Nuclear Receptors in Liver and Digestive Diseases

2006: Symposium Speaker, European Congress of Endocrinology, Glasgow

2005: Invited Speaker, Keystone Symposium on PPARs/LXR, Vancouver

2003: Invited Speaker, Nuclear Receptors and Cardiovascular Disease, San Diego

2001: International Congress of Clinical Pharmacology and Therapeutics, Denmark

2000: Symposium, 11th International Congress of Endocrinology, Sydney

1998: Symposium on Thyroid Hormone Action, Endocrine Society, New Orleans

1996: Symposium, European Thyroid Association, Amsterdam

1995: 12th Symposium on Steroid Receptor Biochemistry and Molecular Biology, Berlin

1994: European Congress of Endocrinology, Amsterdam

1993: Annual Meeting of the European Thyroid Association, Cardiff

Research Experience & Grant Funding:

My 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 PPARγ 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.

Grant Funding

2022 – 2027: Wellcome PhD for Health Professionals Programme (£7.68M) (lead applicant)

2022 – 2029: NIHR Funding for Clinical Research Facilities for Experimental Medicine

(£19.6M) (lead applicant)

2022-2027: NIHR Cambridge Biomedical Centre, Endocrinology subtheme, (£99,565) (co-applicant)

2018 – 2025: Wellcome Investigator Award “Disorders of Thyroid Hormone Action: Diagnosis, Pathophysiology and Therapy” (£1,651,565) (lead applicant)

Publications:

*Coequal first authors; †Coequal corresponding authors

1. Persani L, Rodien P, Moran C, Visser WE, Groeneweg S, Peeters R, Refetoff S, Gurnell M, Beck-Peccoz P, Chatterjee K. 2024 European Thyroid Association Guidelines on diagnosis and management of genetic disorders of thyroid hormone transport, metabolism and action. Eur. Thyroid J. (2024) 13:e240125 PMID:38963712

2. Moran C, Schoenmakers N, Halsall D, Oddy S, Lyons G, van den Berg S, Gurnell M, Chatterjee K. Approach to the patient with raised thyroid hormones and non-suppressed TSH. Journal of Clinical Endocrinology and Metabolism (2024) 109:1094-1108. PMID: 37988295

3. Lockhart SM, Muso M, Zvetkova I, Lam BYH, Ferrari A, Schoenmakers E, Duckett K, Leslie J, Romartinez-Alonso B, Tadross J, Jia R, Gardner EJ, Kentistou K, Zhao Y, Day F, Morseburg A, Rainbow K, Rimmington D, Mastantuoni M, Harrison J, Nus M, Guma’a K, Sherratt-Mayhew S, Jiang X, Smith KR, Paul DS, Jenkins B, Koullman A, Pietzner M, Langenberg C, Wareham N, Yeo GS, Chatterjee K, Schwabe J, Oakley F, Mann D, Tontonoz P, Coll T, Ong K, Perry JRB, O’Rahilly S. Damaging mutations in liver X receptor-a are hepatotoxic and implicate cholesterol sensing in liver health.  Nature Metabolism (2024)6:1922-1938. PMID: 39322746

4. Schoenmakers E, Marelli F, Jorgensen HF, Visser WEV, Moran C, Groeneweg S, Avalos C, Jurgens SJ, Figg N, Finigan A, Wali N, Agostini M, Wardle-Jones H, Lyons G, Rusk R, Gopalan D, Twiss P, Visser J, Goddard M, Nashef S, Heijmen R, Clift P, Sinha S, Pirruccello JP, Ellinor PT, Busch-Nentwich E, Ramirez-Solis R, Persani L, Bennett M, Chatterjee K. Selenoprotein deficiency predisposes to aortic aneurysm formation. Nature Communications (2023) 14:7994. PMID: 38042913.

5. Okosieme OE, Usman D, Taylor PN, Dayan CM, Lyons G, Moran C, Chatterjee K, Rees DA. Cardiovascular morbidity and mortality in patients in Wales, UK with Resistance to Thyroid Hormone b (RTHb): a linked record study. Lancet Diabetes Endocrinol. (2023) 11: 657-666. PMID 37475119

6. Dore R, Watson L, Hollidge S, Krause C, Sentis SC, Oelkrug R, Geisler C, Johann K, Pedaran M, Lyons G, Lopez-Alcantara N, Resch J, Sayk F, Iwen KA, Franke A, Boysen TJ, Dalley JW, Lorenz K, Moran C, Rennie KL, Arner A, Kirchner H, Chatterjee K, Mittag J. Resistance to thyroid hormone induced tachycardia in RTHa syndrome. Nat. Commun. (2023) 14:3312. PMID: 37286550.

7. Moran C and Chatterjee K. Maternal Resistance to Thyroid Hormone b and pregnancy outcomes. J. Clin. Endocrinol. Metab. (2023) 109:e420-e421. PMID 37315195.

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

9. Uter J, Heldmann M, Rogge B, Obst M, Steinhardt J, Brabant G, Moran C, Chatterjee K, Münte TF. Patients with mutations of thyroid hormone beta receptor show an ADHD-like phenotype for performance monitoring: an electrophysiological study. NeuroImage Clin. (2020) 22:102250. PMID: 32217468

10. Moran C, Habeb AM, Kahaly GJ, Campmann C, Hughes M, Mark J, Rajanayagam O, Kuczynski A, Vargha-Khadem F, Morsy M, Offiah AC, Poole K, Ward K, Lyons G, Halsall D, Berman L, Watson L, Baguley D, Mollon J, Moore AT, Holder GE, Dattani M, Chatterjee K.  Homozygous resistance to thyroid hormone β: Can combined anti-thyroid drug and triiodothyroacetic acid treatment prevent cardiac failure? J Endocr. Soc. (2017) 1:1203-1212. PMID:29264576

11. 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 analyses of three related patients Lancet Diabetes Endocrinol. (2014) 2: 619-626. PMID: 24969835

12. 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. A Mutation in the Thyroid Hormone Receptor Alpha Gene. N. Engl. J. Med. (2012) 366:243-249. PMID: 22168587

13. Sun Y*, Bak B*, Schoenmakers N*, van Trotsenburg 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 MG, Breuning MH, Hennekam RC, Chatterjee K†, Dattani MT†, Wit JM†, Bernard DJ†.  Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement.  Nature Genetics (2012) 44: 1375-1381. PMID: 23143598

14. 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 K F†. Resistance to thyroid hormone is associated with raised energy expenditure, muscle mitochondrial uncoupling, and hyperphagia. J. Clin. Invest. (2010) 120:1345-1354. PMID: 20237409

15. 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, Karbaschi 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 K, Cooke M, Semple R, Halsall D, Wareham N, Schwabe J, Grasso L, Beck-Peccoz P, Ogunko A, Dattani M, Gurnell M, Chatterjee K.  Mutations in the selenocysteine insertion sequence-binding protein 2 gene lead to a multisystem selenoprotein deficiency disorder in humans. Journal of Clinical Investigation (2010) 120: 4220-4235. PMID: 21084748

16. Agostini M*, Schoenmakers E*, Mitchell CS, Szatmari I, Savage DB, Smith AG, Rajanayagam O, Luan J, Semple RK, Bath L, Zalin AN, Labib M, Kumar S, Simpson H, Blom D, Marais D, Schwabe JWR, Trembath R, Nagy L, Wareham N, Gurnell M, O’Rahilly S, Chatterjee VKK.  Non-DNA binding, dominant negative, human PPARg mutations causes lipodystrophic insulin resistance. Cell Metabolism (2006) 4: 303-311. PMID: 17011503

17. Kallenberger BC, Love JD, Chatterjee VKK, Schwabe JWR.  A dynamic mechanism of nuclear receptor activation and its perturbation in a human disease.  Nature Structural Biology (2003) 10: 136-140. PMID: 12536206

18. Kahaly GJ, Matthews CH, Mohr-Kalahy S, Richards CA, Chatterjee VKK. Cardiac involvement in thyroid hormone resistance. J. Clin. Endo. Metab. (2002) 87:204-212. PMID:11788648

19. Savage DB*, Agostini M*, Barroso I*, Gurnell M*, Luan JA*, Meirhaeghe A, Harding A-H, Ihrke G, Rajanayagam O, Soos MA, George S, Berger D, Thomas EL, Bell JD, Meeran K, Ross R, Vidal-Puig A, Wareham NJ, O’Rahilly S†, Chatterjee VKK†, Schafer AJ.  Digenic inheritance of severe insulin resistance in a human pedigree.  Nature Genetics (2002) 31: 379-384. PMID: 12118251

20. 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.  Retardation of post-natal development caused by a negatively acting thyroid hormone receptor a1.  EMBO J. (2002) 21: 5079-5087. PMID: 12356724

21. Barroso I*, Gurnell M*, Crowley VEF*, Agostini M, Schwabe JW, Soos MA, Maslen GLI, Williams TDM, Lewis H, Schafer AJ, Chatterjee VKK†, O’Rahilly S†.  Dominant negative mutations in human PPARg are associated with severe insulin resistance, diabetes mellitus and hypertension.  Nature (1999) 402: 880-883. PMID: 10622252

22. Gurnell M*, Wentworth JM*, Agostini M, Adams M, Collingwood TN, Provenzano C, Browne PO, Rajanayagam O, Burris TP, Schwabe JW, Lazar MA, Chatterjee VKK.  A dominant negative PPARg mutant is a constitutive repressor and inhibits PPARg-mediated adipogenesis. Journal of Biological Chemistry (2000) 275: 5754-5759. PMID: 10681562

23. Collingwood TN, Wagner R, Matthews CH, Clifton-Bligh RJ, Gurnell M, Rajanayagam O, Agostini M, Fletterick RJ, Beck-Peccoz P, Reinhardt W, et al and Chatterjee VKK. A role for helix 3 of the TRb ligand binding domain in coactivator recruitment identified by characterization of a third cluster of mutations in resistance to thyroid hormone.  EMBO J. (1998) 17:4760-4770. PMID:9707435

24. Clifton-Bligh RJ, Wentworth JM, Heinz P, Crisp MS, John R, Lazarus JH, Ludgate M, Chatterjee VKK. Mutation of the gene encoding human TTF-2 associated with thyroid agenesis, cleft palate and choanal atresia.  Nature Genetics (1998) 19: 399-401. PMID: 9697705

25. Collingwood TN, Rajanayagam O, Adams M, Wagner R, Cavailles V, Kalkhoven E, Matthews C, Nystrom E, Stenlof K, Lindstedt G, Tisell L, Fletterick RJ, Parker MG, Chatterjee VKK. A natural transactivation mutation in the thyroid hormone receptor: Impaired interaction with putative transcriptional mediators.  Proc. Natl. Acad. Sci. USA (1997) 94: 248-253. PMID: 8990194

26. Matthews CH and Chatterjee VKK.  Isolated deficiency of follicle-stimulating hormone 'Re-revisited'.  N. Engl. J. Med. (1997) 337: 642. PMID: 9280841

27. Adams M, Montague CT, Prins JB, Holder JC, Smith SA, Sanders L, Digby JE, Sewter CP, Lazar MA, Chatterjee VKK, O’Rahilly S. Activators of PPARg have depot-specific effects on human preadipocyte differentiation.  J. Clin. Invest. (1997) 100: 3149-3153. PMID: 9399962

28. Collingwood TN*, Adams M*, Tone Y, Chatterjee VKK. Spectrum of transcriptional dimerization and dominant negative properties of twenty different mutant thyroid hormone b receptors in thyroid hormone resistance syndrome. Mol. Endocrinol. (1994) 8:1262-1277. PMID:7838159

29. Adams M, Matthews CH, Collingwood TN, Tone Y, Beck-Peccoz P, Chatterjee VKK.  Genetic analysis of twenty-nine kindreds with generalised and pituitary resistance to thyroid hormone. J. Clin. Invest. (1994) 94:506-515. PMID:8040303

30. Matthews CH, Borgato S, Beck-Peccoz P, Adams M, Tone Y, Gambino G, Casagrande S, Tedeschini G, Benedetti S, Chatterjee VKK.  Primary amennorhoea and infertility due to a mutation in the b subunit of follicle stimulating hormone.  Nature Genetics (1993) 5: 83-86. PMID: 8220432

31. Chatterjee VKK, Nagaya T, Madison LD, Rentoumis A, Jameson JL. Thyroid hormone resistance syndrome; inhibition of normal receptor function by mutant thyroid receptors. J. Clin. Invest (1991) 87:1977-1984. PMID:2040690

32. Chatterjee VKK, Lee J-K, Rentoumis A and Jameson JL.  Negative regulation of the TSHa-subunit gene by thyroid hormone: a response element localizes to the TATA box.  Proc. Natl. Acad. Sci. USA. (1989) 86: 9114-9118. PMID: 2480596