Korbonits, Márta

Marta Korbonits

Professor in Endocrinology / Deputy Director WHRI

Márta Korbonits graduated in Medicine in Budapest and undertook her early clinical training at the Internal Medicine Department of the Postgraduate Medical School, Budapest. In 1991, she joined the Department of Endocrinology at St. Bartholomew’s Hospital in 1991 under the mentorship of Professors Ashley Grossman and Michael Besser. Her MD and PhD studies contributed to the understanding of the effects of growth hormone secretagogues on hypothalamic hormone release, and the nature and causes of pituitary tumorigenesis. In 2000, she was awarded an MRC Clinician Scientist Fellowship, and commenced studies that produced novel insights into ghrelin physiology and genetics, and had novel findings related to the ghrelin, cannabinoid and glucocorticoid regulation of the metabolic enzyme AMPK. In 2008, she was awarded a Personal Chair as Professor of Endocrinology and Metabolism. Professor Korbonits continues to integrate human studies alongside with laboratory-based research and has pioneered several projects in translational medicine. Over the last decade her major research focus involves the clinical and scientific aspects of familial isolated pituitary adenomas.

In addition to her clinical and basic research, she looks after patients with endocrine diseases in St. Bartholomew’s Hospital, has wide-ranging undergraduate and postgraduate teaching activities and supervises MSc and PhD students. She has received several awards including she is an elected member of the Association of Physicians of Great Britain and Ireland (2009), received the Nicholas T. Zervas Lectureship in Pituitary and Neuroendocrine Disorders at Massachusetts General Hospital (2010),  Society for Endocrinology Medal (2013) and the Endocrine Society Delbert Fischer award (2015). Since 2012 she is Co-Centre Lead for Endocrinology and Since 2016 Depute head of the William Harvey Research Institute. She supports the endocrine community’s learned Societies: served as the Conference Program Secretary for the Society for Endocrinology, was Board member for Pituitary Society and European Neuroendocrine Society and currently she chairs the Science Committee of the European Society of Endocrinology. She is current or past Editorial Board member of Journals of Clinical Endocrinology and Metabolism, Journal and Neuroendocrinology, Pituitary and Journal of Endocrinology and Associate Editor of Scientific Reports, Annals of Human Genetics and the Journal of the Endocrine Society.  

Summary of Research

Pituitary and Neuroendocrine Group

Prof Korbonits is investigating the aetiology and tumorigenic process of familial and sporadic pituitary adenomas. She set up the International FIPA consortium (www.fipapatients.org) and studies the clinical, genetic and molecular characteristics of these patients. A particular focus is the mechanism by which loss-of-function AIP mutations cause particularly aggressive adenomas at a young age, via RNA microarray studies on cell lines and human samples; establishment of animal model in mice and in the fruitfly; dissecting the regulation of AIP expression and the role of AIP in pituitary development (in collaboration with Carles Gaston-Massuet). She has established the genetic alteration in a patient with gigantism from the 18th century and identified the current living families related to this patient. Via her screening efforts lead to early diagnosis and treatment of several pre-symptomatic patients increasing, therefore their chance of better long-term outcome.


AIP Mutations and Gigantism. A. 18th century patient with gigantism due to a mutation of AIP (aryl hydrocarbon receptor interacting protein) beside his twin cousins who also had gigantism, in an etching by John Kay (1742–1826) (National Portrait Gallery, London) (Chahal, NEJM, 2011). B. Ribbon representation of the crystal structure of human AIP (based on data published in Morgan, PlosOne, 2012 and Linnert, Biomol. NMR Assign, 2012) with the stop mutation from the 18th-century patient marked in red. C. A hand of a 4th-year male medical student (172cm tall) compared to the tracing of the hand of an Irish patient from the 18th century with gigantism (tracing from Frankom, G; Musgrave, J.H. The Irish giant, 1974, Duckworth, London).

 

 

www.fipapatients.com

 

Members of the Group

Dr Alejandro Ibanez-Costa, COFUND Marie Curie Postdoctoral Research fellow
Dr Antonia Solomou, Postdoctoral Fellow
Dr Donato Iacovazzo, Diabetes UK Clinical Training Fellow
Ms Karen Young, MRC Clinical Training Fellow
Dr Mary Dang, Database Manager
Dr Nicola Tufton, Clinical Training Fellow
Dr Pedro Marquez, Clinical Training Fellow
Dr Sayka Barry, Postdoctoral Fellow
Mr Xavier Sandin, EU grant manager

Selected Past Lab Members

Dr Blerina Kola, Clinical Training Fellow
Dr Chrysanthia Leontiou, PhD student
Dr Craig Stiles, Wellcome Clinical Training Fellow
Dr Daniela Aflorei, Clinical Training Fellow
Dr Edwin Garcia, Postdoctoral Fellow
Dr Francesco Ferrau, Visiting Clinical Fellow
Dr Giampaolo Trivellin, Postdoctoral Fellow
Dr Harvinder Chahal, MRC Clinical Training Fellow
Dr Erika Hubina, Clinical Training Fellow
Dr Ida Pernicova, Clinical Training Fellow
Dr Julia Thomas, Clinical Training Fellow
Dr Laura Hernandez-Ramirez, Clinical Training Fellow
Dr Marton Doleschall, Postdoctoral Fellow
Dr Mirjam Christ-Crain, Clinical Training Fellow
Dr Pam Gabrovska, Database Manager
Dr Sayka Barry, Postdoctoral Fellow
Dr Serban Radian, Marie Curie Research fellow

Key Publications

For a full list of publist publications click here

1. Rodd, C., Millette, M., Iacovazzo, D., Stiles, C.E., Barry, S., Evanson, J., Albrecht, S., Caswell, R., Bunce, B., Jose, S., Trouillas, J., Roncaroli, F., Sampson, J., Ellard, S. & Korbonits, M. (2016) Somatic GPR101 Duplication Causing X-Linked Acrogigantism (XLAG)-Diagnosis and Management. Journal of Clinical Endocrinology and Metabolism 101, 1927-1930.

2. Radian, S., Diekmann, Y., Gabrovska, P., Holland, B., Bradley, L., Wallace, H., Stals, K., Bussell, A.M., McGurren, K., Cuesta, M., Ryan, A.W., Herincs, M., Hernandez-Ramirez, L.C., Holland, A., Samuels, J., Aflorei, E.D., Barry, S., Denes, J., Pernicova, I., Stiles, C.E., Trivellin, G., McCloskey, R., Ajzensztejn, M., Abid, N., Akker, S.A., Mercado, M., Cohen, M., Thakker, R.V., Baldeweg, S., Barkan, A., Musat, M., Levy, M., Orme, S.M., Unterlander, M., Burger, J., Kumar, A.V., Ellard, S., McPartlin, J., McManus, R., Linden, G.J., Atkinson, B., Balding, D.J., Agha, A., Thompson, C.J., Hunter, S.J., Thomas, M.G., Morrison, P.J. & Korbonits, M. (2016) Increased Population Risk of AIP-Related Acromegaly and Gigantism in Ireland. Human Mutation.

3. Iacovazzo, D., Caswell, R., Bunce, B., Jose, S., Yuan, B., Hernandez-Ramirez, L.C., Kapur, S., Caimari, F., Evanson, J., Ferrau, F., Dang, M.N., Gabrovska, P., Larkin, S.J., Ansorge, O., Rodd, C., Vance, M.L., Ramirez-Renteria, C., Mercado, M., Goldstone, A.P., Buchfelder, M., Burren, C.P., Gurlek, A., Dutta, P., Choong, C.S., Cheetham, T., Trivellin, G., Stratakis, C.A., Lopes, M.B., Grossman, A.B., Trouillas, J., Lupski, J.R., Ellard, S., Sampson, J.R., Roncaroli, F. & Korbonits, M. (2016) Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study. Acta Neuropathol Commun 4, 56.

4. Iacovazzo, D., Carlsen, E., Lugli, F., Chiloiro, S., Piacentini, S., Bianchi, A., Giampietro, A., Mormando, M., Clear, A.J., Doglietto, F., Anile, C., Maira, G., Lauriola, L., Rindi, G., Roncaroli, F., Pontecorvi, A., Korbonits, M. & De Marinis, L. (2016) Factors predicting pasireotide responsiveness in somatotroph pituitary adenomas resistant to first-generation somatostatin analogues: an immunohistochemical study. European Journal of Endocrinology 174, 241-250.

5. Hernández-Ramírez, L.C., Martucci, F., Morgan, R.M., Trivellin, G., Tilley, D., Ramos-Guajardo, N., Iacovazzo, D., D'Acquisto, F., Prodromou, C. & Korbonits, M. (2016) Rapid proteasomal degradation of mutant proteins is the primary mechanism leading to tumorigenesis in patients with missense AIP mutations. Journal of Clinical Endocrinology and Metabolism 101, 3144-3154.

6. Caimari, F. & Korbonits, M. (2016) Novel genetic causes of pituitary adenomas. Clinical Cancer Research 22, 5030-5042.

7. Bolger, G.B., Bizzi, M.F., Pinheiro, S.V., Trivellin, G., Smoot, L., Accavitti, M.A., Korbonits, M. & Ribeiro-Oliveira, A., Jr. (2016) cAMP-specific PDE4 phosphodiesterases and AIP in the pathogenesis of pituitary tumors. Endocrine-Related Cancer 23, 419-431.

8. Hernández-Ramírez, L.C., Gabrovska, P., Dénes, J., Stals, K., Trivellin, G., Tilley, D., Ferraù, F., Evanson, J., Ellard, S., Grossman, A.B., Roncaroli, F., Gadelha, M.R., Korbonits, M. & Consortium., T.I.F. (2015) Landscape of familial isolated and young-onset pituitary adenomas: prospective diagnosis in AIP mutation carriers. Journal of Clinical Endocrinology and Metabolism 100, E1242-1254.

9. Ferrau, F. & Korbonits, M. (2015) Metabolic comorbidities in Cushing's syndrome. European Journal of Endocrinology 173, M133-157.

10. Dénes, J., Swords, F., Rattenberry, E., Stals, K., Owens, M., Cranston, T., Xekouki, P., Moran, L., Kumar, A., Wassif, C., Fersht, N., Baldeweg, S.E., Morris, D., Lightman, S., Agha, A., Rees, A., Grieve, J., Powell, M., Boguszewski, C.L., Dutta, P., Thakker, R.V., Srirangalingam, U., Thompson, C.J., Druce, M., Higham, C., Davis, J., Eeles, R., Stevenson, M., O'Sullivan, B., Taniere, P., Skordilis, K., Gabrovska, P., Barlier, A., Webb, S.M., Aulinas, A., Drake, W.M., Bevan, J.S., Preda, C., Dalantaeva, N., Ribeiro-Oliveira, A., Jr., Tena, G., I, Yordanova, G., Iotova, V., Evanson, J., Grossman, A.B., Trouillas, J., Ellard, S., Stratakis, C.A., Maher, E.R., Roncaroli, F. & Korbonits, M. (2015) Heterogeneous genetic background of the association of pheochromocytoma/paraganglioma and pituitary adenoma - results from a large patient cohort. Journal of Clinical Endocrinology and Metabolism 100, E531-E541.

11. Dénes, J., Kasuki, L., Trivellin, G., Colli, L.M., Takiya, C.M., Stiles, C.E., Barry, S., De Castro, M., Gadelha, M.R. & Korbonits, M. (2015) Regulation of aryl hydrocarbon receptor interacting protein (AIP) protein expression by miR-34a in sporadic somatotropinomas. PloS One 10, e0117107.

12. Williams, F., Hunter, S., Bradley, L., Chahal, H.S., Storr, H., Akker, S.A., Kumar, A.V., Orme, S.M., Evanson, J., Morrison, P.J., Korbonits, M. & Atkinson, A.B. (2014) Clinical experience in the screening and management of a large kindred with familial isolated pituitary adenoma due to an aryl hydrocarbon receptor interacting protein (AIP) mutation. Journal of Clinical Endocrinology and Metabolism 99, 1122-1131.

13. Pernicova, I. & Korbonits, M. (2014) Metformin--mode of action and clinical implications for diabetes and cancer. Nat. Rev. Endocrinol 10, 143-156.

14. Larkin, S.J., Ferraù, F., Karavitaki, N., Hernández-Ramírez, L.C., Ansorge, O., Grossman, A.B. & Korbonits, M. (2014) Sequence analysis of the catalytic subunit of PKA in somatotroph adenomas. European Journal of Endocrinology 171, 705-710.

15. Kola, B., Wittman, G., Bodnar, I., Amin, F., Lim, C.T., Olah, M., Christ-Crain, M., Lolli, F., van, T.H., Leontiou, C.A., Fuzesi, T., Dalino, P., Isidori, A.M., Harvey-White, J., Kunos, G., Nagy, G.M., Grossman, A.B., Fekete, C. & Korbonits, M. (2013) The CB1 receptor mediates the peripheral effects of ghrelin on AMPK activity but not on growth hormone release. FASEB Journal 27, 5112-5121.

16. Garcia, E.A., Trivellin, G., Aflorei, E.D., Powell, M., Grieve, J., Alusi, G., Pobereskin, L., Shariati, B., Cudlip, S., Roncaroli, F., Mendoza, N., Grossman, A.B., Harper, E.A. & Korbonits, M. (2013) Characterization of SNARE proteins in human pituitary adenomas: targeted secretion inhibitors as a new strategy for the treatment of acromegaly? Journal of Clinical Endocrinology and Metabolism 98, E1918-E1926.

17. Trivellin, G., Butz, H., Delhove, J., Igreja, S., Chahal, H.S., Zivkovic, V., McKay, T., Patocs, A., Grossman, A.B. & Korbonits, M. (2012) MicroRNA miR-107 is overexpressed in pituitary adenomas and in vitro inhibits the expression of aryl hydrocarbon receptor-interacting protein (AIP). Am. J. Physiol. Endocrinol. Metab 303, E708-E719.

18. Korbonits, M., Storr, H. & Kumar, A.V. (2012) Familial pituitary adenomas - Who should be tested for AIP mutations? Clinical Endocrinology 77, 351-356.

19. Chahal, H.S., Trivellin, G., Leontiou, C.A., Alband, N., Fowkes, R.C., Tahir, A., Igreja, S.C., Chapple, J.P., Jordan, S., Lupp, A., Schulz, S., Ansorge, O., Karavitaki, N., Carlsen, E., Wass, J.A., Grossman, A.B. & Korbonits, M. (2012) Somatostatin analogs modulate AIP in somatotroph adenomas: the role of the ZAC1 pathway. Journal of Clinical Endocrinology and Metabolism 97, E1411-E1420.

20. Trivellin, G. & Korbonits, M. (2011) AIP and its interacting partners. J. Endocrinol 210, 137-155.

21. Chahal, H.S., Stals, K., Unterlander, M., Balding, D.J., Thomas, M.G., Kumar, A.V., Besser, G.M., Atkinson, A.B., Morrison, P.J., Howlett, T.A., Levy, M.J., Orme, S.M., Akker, S.A., Abel, R.L., Grossman, A.B., Burger, J., Ellard, S. & Korbonits, M. (2011) AIP mutation in pituitary adenomas in the 18th century and today. N. Engl. J. Med 364, 43-50.

22. Igreja, S., Chahal, H.S., King, P., Bolger, G.B., Srirangalingam, U., Guasti, L., Chapple, J.P., Trivellin, G., Gueorguiev, M., Guegan, K., Stals, K., Khoo, B., Kumar, A.V., Ellard, S., Grossman, A.B. & Korbonits, M. (2010) Characterization of aryl hydrocarbon receptor interacting protein (AIP) mutations in familial isolated pituitary adenoma families. Human Mutation 31, 950-960.

23. Ribeiro-Oliveira, A., Jr., Franchi, G., Kola, B., Dalino, P., Pinheiro, S.V., Salahuddin, N., Musat, M., Góth, M.I., Czirjak, S., Hanzély, Z., da Silva, D.A., Jr, P.E., Grossman, A.B. & Korbonits, M. (2008) Protein western array analysis in human pituitary tumours: insights and limitations. Endocrine-Related Cancer 15, 1099-1114.

24. Leontiou, C.A., Gueorguiev, M., J., v.d.S., Quinton, R., Lolli, F., Hassan, S., Chahal, H.S., Igreja, S.C., Jordan, S., Rowe, J., Stolbrink, M., Christian, H.C., Wray, J., Bishop-Bailey, D., Berney, D.M., Wass, J.A., Popovic, V., Ribeiro-Oliveira, A., Jr., Gadelha, M.R., Monson, J.P., Akker, S.A., Davis, J.R., Clayton, R.N., Yoshimoto, K., Iwata, T., Matsuno, A., Eguchi, K., Musat, M., Flanagan, D., Peters, G., Bolger, G.B., Chapple, J.P., Frohman, L.A., Grossman, A.B. & Korbonits, M. (2008) The role of the aryl hydrocarbon receptor-interacting protein gene in familial and sporadic pituitary adenomas. Journal of Clinical Endocrinology and Metabolism 93, 2390-2401.

25. Kola, B., Farkas, I., Christ-Crain, M., Wittmann, G., Lolli, F., Amin, F., Harvey-White, J., Liposits, Z., Kunos, G., Grossman, A.B., Fekete, C. & Korbonits, M. (2008) The orexigenic effect of ghrelin is mediated through central activation of the endogenous cannabinoid system. PloS One 3, e1797.

26. Kola, B., Christ-Crain, M., Lolli, F., Arnaldi, G., Giacchetti, G., Boscaro, M., Grossman, A.B. & Korbonits, M. (2008) Changes in adenosine 5'-monophosphate-activated protein kinase as a mechanism of visceral obesity in Cushing's syndrome. Journal of Clinical Endocrinology and Metabolism 93, 4969-4973.

27. Christ-Crain, M., Kola, B., Lolli, F., Fekete, C., Seboek, D., Wittmann, G., Feltrin, D., Igreja, S.C., Ajodha, S., Harvey-White, J., Kunos, G., Muller, B., Pralong, F., Aubert, G., Arnaldi, G., Giacchetti, G., Boscaro, M., Grossman, A.B. & Korbonits, M. (2008) AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome. FASEB Journal 22, 1672-1683.

28. Korbonits, M., Blaine, D., Elia, M. & Powell-Tuck, J. (2007) Metabolic and hormonal changes during the refeeding period of prolonged fasting. European Journal of Endocrinology 157, 157-166.

29. Korbonits, M., Blaine, D., Elia, M. & Powell-Tuck, J. (2005) Refeeding Blaine: studies following a 44 day fast. New England Journal of Medicine 353, 2307-2308.

30. Kola, B., Hubina, E., Tucci, S.A., Kirkham, T.C., Garcia, E.A., Mitchell, S.E., Williams, L.M., Hawley, S.A., Hardie, D.G., Grossman, A.B. & Korbonits, M. (2005) Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase. J. Biol. Chem 280, 25196-25201.

31. Nanzer, A.M., Khalaf, S., Mozid, A.M., Fowkes, R.C., Patel, M.V., Burrin, J.M., Grossman, A.B. & Korbonits, M. (2004) Ghrelin exerts a proliferative effect on a rat pituitary somatotroph cell line via the mitogen-activated protein kinase pathway. European Journal of Endocrinology 151, 233-240.

32. Korbonits, M., Gueorguiev, M., O'Grady, E., Lecoeur, C., Swan, D.C., Mein, C.A., Weill, J., Grossman, A.B. & Froguel, P. (2002) A variation in the ghrelin gene increases weight and decreases insulin secretion in tall, obese children. Journal of Clinical Endocrinology and Metabolism 87, 4005-4008.

33. Gnanapavan, S., Kola, B., Bustin, S.A., Morris, D.G., McGee, P., Fairclough, P., Bhattacharya, S., Carpenter, R., Grossman, A.B. & Korbonits, M. (2002) The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. Journal of Clinical Endocrinology and Metabolism 87, 2988-2991.

34. Korbonits, M., Bustin, S.A., Kojima, M., Jordan, S., Adams, E.F., Lowe, D.G., Kangawa, K. & Grossman, A.B. (2001) The expression of the growth hormone secretagogue receptor ligand ghrelin in normal and abnormal human pituitary and other neuroendocrine tumors. Journal of Clinical Endocrinology and Metabolism 86, 881-887.

35. Korbonits, M., Bujalska, I., Shimojo, M., Nobes, J., Jordan, S., Grossman, A.B. & Stewart, P.M. (2001) Expression of 11 beta-hydroxysteroid dehydrogenase isoenzymes in the human pituitary: induction of the type 2 enzyme in corticotropinomas and other pituitary tumors. Journal of Clinical Endocrinology and Metabolism 86, 2728-2733.

36. Hayward, B.E., Barlier, A., Korbonits, M., Grossman, A.B., Jacquet, P., Enjalbert, A. & Bonthron, D.T. (2001) Imprinting of the G(s)alpha gene GNAS1 in the pathogenesis of acromegaly. Journal of Clinical Investigation 107, R31-R36.

37. Lidhar, K., Korbonits, M., Jordan, S., Khalimova, Z., Kaltsas, G., Lu, X., Clayton, R.N., Jenkins, P.J., Monson, J.P., Besser, G.M., Lowe, D.G. & Grossman, A.B. (1999) Low expression of the cell cycle inhibitor p27Kip1 in normal corticotroph cells, corticotroph tumors, and malignant pituitary tumors. Journal of Clinical Endocrinology and Metabolism 84, 3823-3830.

38. Korbonits, M., Kaltsas, G., Perry, L.A., Putignano, P., Grossman, A.B., Besser, G.M. & Trainer, P.J. (1999) The growth hormone secretagogue hexarelin stimulates the hypothalamo-pituitary-adrenal axis via arginine vasopressin. Journal of Clinical Endocrinology and Metabolism 84, 2489-2495.

39. Korbonits, M., Jacobs, R.A., Aylwin, S.J.B., Burrin, J.M., Dahia, P.L.M., Monson, J.P., Trainer, P.J., Chew, S.L., Besser, G.M. & Grossman, A.B. (1998) Expression of the growth hormone secretagogue receptor in pituitary adenomas and other neuroendocrine tumors. Journal of Clinical Endocrinology and Metabolism 83, 3624-3630.

40. Korbonits, M., Trainer, P.J., Nelson, M.L., Howse, I., Kopelman, P.G., Besser, G.M., Grossman, A.B. & Svec, F. (1996) Differential stimulation of cortisol and dehydroepiandrosterone levels by food in obese and normal subjects: relation to body fat distribution. Clinical Endocrinology 45, 699-706.

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