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The William Harvey Research Institute - Faculty of Medicine and Dentistry

Dr Carles Gaston-Massuet


Reader in Developmental Genetics and Endocrinology

Centre: Endocrinology

Telephone: +44(0) 20 7882 2115


ORCID iD: 0000-0002-6793-3118

I graduated in Medical Sciences from Barcelona University with exchange programme at King’s College London University. I undertook my PhD studies in Developmental Molecular Biology in Professor Andrew Copp’s laboratory at University College London Institute of Child Health. My thesis work involved analyses of congenital birth defects of the central nervous system. I then joined the group Dr Martinez-Barbera to study congenital abnormalities of hypothalamic-pituitary axis development. In 2009, I was awarded a Research Fellowship from the National Institute of Health Research to specialise in the genetics of rare endocrine diseases in children, from paediatric tumours called adamantinomatous cranyoparhyngioma to the identification of genes that cause congenital forms of hypothalamic-pituitary dysfunction.

In February 2013, I was awarded an Early Career Fellowship through an open base competition to start my own independent research group at the Centre for Endocrinology within the William Harvey Research Institute at Queen Mary University London and Saint Bartholomew's Hospital. Since 2013 I have obtained external funding from several grant funding bodies and Research Councils, among others: Action Medical Research for Sick Children; Barts and The London Strategic Body, Barts Cancer Institute, Children with Cancer Research UK, Medical Research Council, The Rose-Tree Foundation, Marie-Curie WHRI-Co-Fund, the Society of Endocrinology, British Society for Neuroendocrinology, Joan Adams Fellowships. I was awarded the Fellow of Higher Education Academy of the UK (Distinction) from the Institute of Learning University of London and, promoted to my current position as Group Leader & Senior Lecturer in Genetics and Endocrinology.


Group members

Developmental Genetics and Tumorigenesis Group  

Ms Valeria Scagliotti, Research Assistant, PhD Student
Ms Angelica Gualtieri, Research Assistant
Dr Nikolina Kyprianou, BTLC Clinical Fellowship
Dr Rachael Tan, MRC-PhD Studentship
Mr James Gervace Nicholson, MRC-PhD Studentship

Co-supervising with Professor Marta Korbonits

Dr Antonia Solomou, PhD, MRC-funded Postdoctoral Researcher 
Dr Alejandro Ibáñez-Costa, PhD, Marie-Curie Co-fund Postdoctoral Researcher 
Ms Maria Lillina Vignola, Research Assistant


The hypothalamic-pituitary (HP-axis) is critical for life as it regulates body homeostasis through the secretion of hormones that control vital biological functions such as metabolism, fertility, reproduction, stress response, lactation, growth and electrolyte balance among others. Aberrant pituitary function often results from abnormal development of the hypothalamic-pituitary axis, leading to congenital hypopituitarism, characterised by absent or low-level secretion of one or more hormones. The molecular mechanisms that dictate the congruent development of the HP-axis, and how these mechanisms interact to create a master regulator of body homeostasis is poorly understood. Moreover, our understanding of how this adult organ adapts its plasticity to meet endocrine challenges such as pregnancy and obesity remains in its infancy. Within my group, we have identified genes that are important for the development and homeostasis of this endocrine master regulator. We have, for example, discovered that the Wnt/beta-catenin pathway is critical for maintaining the progenitor pituitary pool and that mutations within genes on this pathway lead to severe endocrine diseases such as paediatric pituitary tumours and congenital hypopituitarism. Our research has also shown that crosstalk between Wnt/beta-catenin and Eph-EphrinB signaling mediates the cellular differentiation of hormone-producing cells and adult organ homeostasis. By identifying key molecular regulators, we have discovered genes that play a critical role in diseases such as infertility, growth restriction and pituitary tumours in humans. Unravelling how these molecules orchestrate the congruent development and maintenance of endocrine cells under hypothalamic inputs will allow us to understand the etiologies of complex congenital hypothalamic-pituitary conditions.

Specific projects

1) Using a transgenic approach, we have generated a murine model that demonstrates that over-activation of Wnt signaling causes Adamantinomatous craniopharyngioma (ACP). This pituitary tumor, which mainly occurs in children, is often invasive and hence affects the hypothalamus and optic nerve, leading to severe endocrine dysfunction and high morbidity. We are using this model to pharmacologically identify novel therapeutics for treating ACP tumors. 

2) From a genetic screen we have identified that the Eph:EphrinBs pathway contributes to both hypothalamic-pituitary development and Wnt-mediated tumorigenesis (Fig). Using tissue-specific transgenic modification, we are establishing the requirement for Eph:EphrinBs in hypothalamic-pituitary (HP) development and assessing its role in oncogenic HP tumorigenesis.

Embryonic development of the hypothalamus and the pituitary gland

Embryonic development of the hypothalamus and the pituitary gland: A) Detection of Efnb2 GFP+ve cells during embryogenesis. B) Efnb2 GFP+ve cells mark anterior pituitary gland and the ventral diencephalon (prospective hypothalamus). C) EfnB2 GFP+ve cells partially localises with pituitary stem cell marker Sox2 (red). D) Abnormal development of anterior pituitary gland during development leading to a pituitary tumour (AP, anterior pituitary; PP posterior pituitary gland).

Key Publications

For a full list of pubmed publications click here

  • Giri D, Vignola ML, Gualtieri A, Scagliotti V, McNamara P, Peak M, Didi M, Gaston-Massuet C, and Senniappan S. Novel FOXA2 Mutation Causes Hyperinsulinism, Hypopitutarism with Craniofacial and Endoderm-Derived Organ Abnormalities. Human molecular genetics.
  • Gaston-Massuet, C., McCabe, M.J., Scagliotti. V.,  Gregory L, An ChWu., Jaques, T.S., Gerrelli, D., Farooqi, I.S., Raza, J., Dattani, M.T., Martinez-Barbera, J.P. Transcription factor 7-like 1 is involved in hypothalamic pituitary axis development in mice and humans. Proc Natl Acad Sci USA 2011. 2016 Feb 2;113 (5):E548-57. 
  • Scagliotti, V., Avagliano, L., Graziola, F., Gualtieri, A., Doi., P, Buftamante, G., Jacques TS.,Korbonits, M, Massa V,Gaston-Massuet, C. Histopatological and molecular characterisation of a new form of  intrauterine diagnosed congenital Craniopharyngioma. Pituitary September. 2635026. 
  • Avagliano L, Doi P, Tosi D, Scagliotti V, Gualtieri A, Gaston-Massuet C, Pistocchi A, Gallina A, Marconi AM, Bulfamante G, Massa V.Cell death and cell proliferation in human spina bifida. Birth Defects Res A Clin Mol Teratol. 2015 Dec 10. doi: 10.1002/bdra.23466. 
  • Fazio G*, Gaston-Massuet C*, Bettini LR, Graziola F, Scagliotti V, Cereda A, Ferrari L, Mazzola M, Cazzaniga G, Giordano A, Cotelli F, Bellipanni G, Biondi A, Selicorni A, Pistocchi A, Massa V. CyclinD1 Down-Regulation and Increased Apoptosis Are Common Features of Cohesinopathies. J Cell Physiol. 2016 Mar;231(3):613-22. * Co-joint first author
  • Gregory, L. C., Gaston-Massuet, C., Andoniadou, C. L., Carreno, G., Webb, E. A., Kelberman, D., McCabe, M. J., Panagiotakopoulos, L., Saldanha, J. W., Spoudeas, H. A., Torpiano, J., Rossi, M., Raine, J., Canham, N., Martinez-Barbera, J. P., and Dattani, M. T. (2014) The role of the sonic hedgehog signalling pathway in patients with midline defects and congenital hypopituitarism. Clinical endocrinology 
  • McCabe MJ, Hu Y, Gregory LC, Gaston-Massuet C, Alatzouglou Ks, Saladanha JW, Gualtierri A, Thankomony A, Huges I, Townshend S, Martinez-Barbera JP, Bouloux PM, Dattani MT. Novel application of liciferase assay for the in vitro functional assessment of KAL1 variants in three female with speto-optic dysplasiaMol Cell Endo 2015 Dec 5;417:63-72. 
  • Andoniadou, C. L., Matsushima, D., Mousavy Gharavy, S. N., Signore, M., Mackintosh, A. I., Schaeffer, M., Gaston-Massuet, C., Mollard, P., Jacques, T. S., Le Tissier, P., Dattani, M. T., Pevny, L. H., and Martinez-Barbera, J. P. (2013) Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential. Cell stem cell 13, 433-445
  • Gaston-Massuet, C*., McCabe, M. J*., Gregory, L. C., Alatzoglou, K. S., Tziaferi, V., Sbai, O., Rondard, P., Masumoto, K. H., Nagano, M., Shigeyoshi, Y., Pfeifer, M., Hulse, T., Buchanan, C. R., Pitteloud, N., Martinez-Barbera, J. P., and Dattani, M. T. (2013) Variations in PROKR2, but not PROK2, are associated with hypopituitarism and septo-optic dysplasia. J.Clin.Endocrinol.Metabolism 98, E547-557 *Equal Contribution.  
  • Jayakody, S. A., Andoniadou, C. L., Gaston-Massuet, C., Signore, M., Cariboni, A., Bouloux, P. M., Le Tissier, P., Pevny, L. H., Dattani, M. T., and Martinez-Barbera, J. P. (2012) SOX2 regulates the hypothalamic-pituitary axis at multiple levels. The Journal of clinical investigation 122, 3635-3646
  • Andoniadou, C. L., Gaston-Massuet, C., Reddy, R., Schneider, R. P., Blasco, M. A., Le Tissier, P., Jacques, T. S., Pevny, L. H., Dattani, M. T., and Martinez-Barbera, J. P. (2012) Identification of novel pathways involved in the pathogenesis of human adamantinomatous craniopharyngioma. Acta neuropathologica 124, 259-271
  • Andoniadou, C. L., Signore, M., Sajedi, E., Gaston-Massuet, C., Kelberman, D., Burns, A. J., Itasaki, N., Dattani, M., and Martinez-Barbera, J. P. (2007) Lack of the murine homeobox gene Hesx1 leads to a posterior transformation of the anterior forebrain. Development 134, 1499-1508
  • Gaston-Massuet, C*., McCabe, M*. J., Tziaferi, V., Gregory, L. C., Alatzoglou, K. S., Signore, M., Puelles, E., Gerrelli, D., Farooqi, I. S., Raza, J., Walker, J., Kavanaugh, S. I., Tsai, P. S., Pitteloud, N., Martinez-Barbera, J. P., and Dattani, M. T. (2011) Novel FGF8 mutations associated with recessive holoprosencephaly, craniofacial defects, and hypothalamo-pituitary dysfunction. J.Clin.Endocrinol.Metab 96, E1709-E1718 * equal contribution
  • Gaston-Massuet, C*., Andoniadou, C. L*., Signore, M., Jayakody, S. A., Charolidi, N., Kyeyune, R., Vernay, B., Jacques, T. S., Taketo, M. M., Le Tissier, P., Dattani, M. T., and Martinez-Barbera, J. P. (2011) Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans. Proc Natl Acad Sci USA 2011 July 108, 11482-11487* equal contribution.
  • Sottocornola, R., Royer, C., Vives, V., Tordella, L., Zhong, S., Wang, Y., Ratnayaka, I., Shipman, M., Cheung, A., Gaston-Massuet, C., Ferretti, P., Molnar, Z., and Lu, X. (2010) ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development. Dev.Cell 19, 126-137
  • Gaston-Massuet, C., Kelberman, D., Dattani, M., and Martinez-Barbera, J. P. (2009) Absence of SIX3 mutations in patients with congenital hypopituitarism. Am.J.Med.Genet.A 149A, 2874-2876 
  • Sajedi, E., Gaston-Massuet, C., Signore, M., Andoniadou, C. L., Kelberman, D., Castro, S., Etchevers, H. C., Gerrelli, D., Dattani, M. T., and Martinez-Barbera, J. P. (2008) Analysis of mouse models carrying the I26T and R160C substitutions in the transcriptional repressor HESX1 as models for septo-optic dysplasia and hypopituitarism. Dis.Model.Mech. 1, 241-254
  • Sajedi, E., Gaston-Massuet, C., Andoniadou, C. L., Signore, M., Hurd, P. J., Dattani, M., and Martinez-Barbera, J. P. (2008) DNMT1 interacts with the developmental transcriptional repressor HESX1. Biochimica et biophysica acta 1783, 131-143
  • Ybot-Gonzalez, P., Gaston-Massuet, C., Girdler, G., Klingensmith, J., Arkell, R., Greene, N. D., and Copp, A. J. (2007) Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling. Development 134, 3203-3211
  • Andoniadou, C. L., Signore, M., Sajedi, E., Gaston-Massuet, C., Kelberman, D., Burns, A. J., Itasaki, N., Dattani, M., and Martinez-Barbera, J. P. (2007) Lack of the murine homeobox gene Hesx1 leads to a posterior transformation of the anterior forebrain. Development 134, 1499-1508
  • Andoniadou, C. L., Signore, M., Young, R. M., Gaston-Massuet, C., Wilson, S. W., Fuchs, E., and Martinez-Barbera, J. P. (2011) HESX1- and TCF3-mediated repression of Wnt/beta-catenin targets is required for normal development of the anterior forebrain. Development 138, 4931-4942 
  • Gaston-Massuet, C., Henderson, D. J., Greene, N. D., and Copp, A. J. (2005) Zic4, a zinc-finger transcription factor, is expressed in the developing mouse nervous system. Dev.Dyn. 233, 1110-1115 
  • Murdoch, J. N., Henderson, D. J., Doudney, K., Gaston-Massuet, C., Phillips, H. M., Paternotte, C., Arkell, R., Stanier, P., and Copp, A. J. (2003) Disruption of scribble (Scrb1) causes severe neural tube defects in the circletail mouse. Hum.Mol.Genet. 12, 87-98

* Equal contribution 




Head of the Mouse Cyro-Preservation SMD Transgenic Unit: Co-supervised by Angelica Guiltier  

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