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Dr Carles Gaston-Massuet

Carles

Reader in Developmental Genetics and Endocrinology

Centre: Endocrinology

Email: c.gaston-massuet@qmul.ac.uk
Telephone: +44(0) 20 7882 2115

Profile

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.

Research

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)

Summary 

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).

Publications

  • Rolas L, Stein M, Barkaway A et al. (2024). Senescent endothelial cells promote pathogenic neutrophil trafficking in inflamed tissues. nameOfConference


  • Garcia-Rendueles AR, Chenlo M, Oroz-Gonjar F et al. (2023). Correction: RET signalling provides tumorigenic mechanism and tissue specificity for AIP-related somatotrophinomas. nameOfConference


  • Scagliotti V, Vignola ML, Willis T et al. (publicationYear). Imprinted Dlk1 dosage as a size determinant of the mammalian pituitary gland. nameOfConference


    QMRO: qmroHref
  • Escuin S, Rose Raza-Knight S, Savery D et al. (2023). Dual mechanism underlying failure of neural tube closure in the Zic2 mutant mouse.. nameOfConference


    QMRO: qmroHref
  • Rai A, Yelamanchi SD, Radotra BD et al. (publicationYear). Phosphorylation of β-catenin at Serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours. nameOfConference


  • Glaser J, Iranzo J, Borensztein M et al. (publicationYear). The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates. nameOfConference


    QMRO: qmroHref
  • Rai A, Yelamanchi SD, Radotra BD et al. (2021). Hyper-phosphorylation of [beta]-catenin at Serine552 correlates with invasion and predicts recurrence of Non-Functioning Pituitary Tumours (NFPTs). BES2021


  • Garcia-Rendueles AR, Chenlo M, Oroz-Gonjar F et al. (2021). RET signalling provides tumorigenic mechanism and tissue specificity for AIP-related somatotrophinomas. nameOfConference


  • Thomas B, Eldridge S, Nosrati B et al. (2021). WNT3A-loaded exosomes enable cartilage repair. nameOfConference


  • Kaygusuz SB, Ates EA, Vignola ML et al. (2021). Dysgenesis and Dysfunction of the Pancreas and Pituitary Due to FOXA2 Gene Defects. nameOfConference


    QMRO: qmroHref
  • Correia JC, Corral LG, Kaygusuz SB et al. (2021). FOXA2 as a Candidate Gene Responsible for Congenital Panhypopituitarism: A Review of the Literature. nameOfConference


    QMRO: qmroHref
  • Gualtieri A, Kyprianou N, Gregory LC et al. (publicationYear). Activating mutations in BRAF disrupt the hypothalamo-pituitary axis leading to hypopituitarism in mice and humans. nameOfConference


  • Chatterjee S, Bertola DR, Agwu C et al. (2021). Novel LZTR1 mutations in subjects with features of Noonan Syndrome and GH insensitivity negatively regulate GH-induced IGF-I production and hyperactivate GH-induced ERK1/2 activation in response to GH in vitro. nameOfConference

    DOI: doi

  • Crescente M, Armstrong PC, Kirkby NS et al. (publicationYear). Profiling the eicosanoid networks that underlie the anti- and pro-thrombotic effects of aspirin. nameOfConference


  • Oleari R, André V, Lettieri A et al. (2021). A Novel SEMA3G Mutation in Two Siblings Affected by Syndromic GnRH Deficiency. nameOfConference


    QMRO: qmroHref
  • Kyprianou N, Blackburn J, Tan R et al. (publicationYear). A novel clinical risk score that accurately predicts recurrence of craniopharyngioma - a multicentre cohort study. nameOfConference


  • Mariniello K, Ruiz-Babot G, McGaugh EC et al. (publicationYear). Stem Cells, Self-Renewal, and Lineage Commitment in the Endocrine System. nameOfConference


  • Mistry A, Solomou A, Vignola ML et al. (publicationYear). Investigating the role of AIP in pituitary tumourigenesis. nameOfConference


    QMRO: qmroHref
  • Bollington M, Mistry A, Solomou A et al. (publicationYear). Transcriptomic analyses reveal deregulation of focal adhesion pathway in Aip KO mice and AIP mutation positive human tumours. nameOfConference


    QMRO: qmroHref
  • Mitchell JA, Shala F, Elghazouli Y et al. (2019). Cell-Specific Gene Deletion Reveals the Antithrombotic Function of COX1 and Explains the Vascular COX1/Prostacyclin Paradox. nameOfConference


  • Ewans LJ, Colley A, Gaston-Massuet C et al. (2019). Pathogenic variants in PLOD3 result in a Stickler syndrome-like connective tissue disorder with vascular complications. nameOfConference


    QMRO: qmroHref
  • Macdougall CE, Wood EG, Solomou A et al. (2019). Constitutive Activation of β-Catenin in Conventional Dendritic Cells Increases the Insulin Reserve to Ameliorate the Development of Type 2 Diabetes in Mice. nameOfConference


  • Gregory LC, Ferreira CB, Young-Baird SK et al. (2019). Impaired EIF2S3 function associated with a novel phenotype of X-linked hypopituitarism with glucose dysregulation. nameOfConference


    QMRO: qmroHref
  • Barry S, Carlsen E, Marques P et al. (2019). Tumor microenvironment defines the invasive phenotype of AIP-mutation-positive pituitary tumors. nameOfConference


  • Macdougall CE, Wood EG, Loschko J et al. (2018). Visceral Adipose Tissue Immune Homeostasis Is Regulated by the Crosstalk between Adipocytes and Dendritic Cell Subsets. nameOfConference


  • Bettini LR, Graziola F, Fazio G et al. (publicationYear). Rings and Bricks: Expression of Cohesin Components is Dynamic during Development and Adult Life. nameOfConference


  • Macdougall C, Wood E, Charalambous M et al. (2018). Investigating β-catenin signalling in conventional dendritic cells in obesity-induced tissue inflammation. nameOfConference

    DOI: doi

    QMRO: qmroHref
  • Giri D, Vignola ML, Gualtieri A et al. (publicationYear). Novel FOXA2 mutation causes hyperinsulinism, hypopituitarism with craniofacial dysmorphism and endoderm-derived organ abnormalities. nameOfConference


    QMRO: qmroHref
  • Kyprianou N, Gregory L, Vignola ML et al. (publicationYear). The MAPK effector B-Raf is essential for hypothalamic-pituitary axis development and activating mutations in BRAF Cause Congenital hypopituitarism. nameOfConference


    QMRO: qmroHref
  • Barry S, Solomou A, Vignola L et al. (publicationYear). A comprehensive analysis of the AIP mutation positive pituitary tumour microenvironment: role of stromal cells and the pro-inflammatory cytokine network. nameOfConference


    QMRO: qmroHref
  • Scagliotti V, Gutierrez LP, Gualtieri A et al. (publicationYear). Cyclooxygenase-2 is a potential target for the treatment of Adamantinomatous craniopharyngioma. nameOfConference


    QMRO: qmroHref
  • Solomou A, Herincs M, Roncaroli F et al. (publicationYear). Investigating the role of AIP in mouse pituitary adenoma formation. nameOfConference


    QMRO: qmroHref
  • Kyprianou N, Gregory L, Lillina VM et al. (publicationYear). The MAPK effector B-Raf is essential for hypothalamic-pituitary axis development and activating mutations in BRAF cause congenital hypopituitarism. nameOfConference


    QMRO: qmroHref
  • Giri D, Vignola ML, Gualtieri A et al. (2017). Novel FOXA2 mutation causes Hyperinsulinism, Hypopituitarism with Craniofacial and Endoderm-derived organ abnormalities. nameOfConference


  • Jimenez FA, Gualtieri A, Scagliotti V et al. (2017). Ephrin-B2 is critical regulator of endocrine organ development. nameOfConference


    QMRO: qmroHref
  • Crescente M, Armstrong PC, CHAN MV et al. (2017). PLATELET COX-1 KNOCKOUT MOUSE AS A MODEL OF THE EFFECTS OF ASPIRIN IN THE CARDIOVASCULAR SYSTEM. BCS Annual Conference, ‘Cardiology at the Extremes'


    QMRO: qmroHref
  • Jimenez F, Gualtieri A, Scagliotti V et al. (publicationYear). Ephrin-B2 is required for pituitary development. nameOfConference


    QMRO: qmroHref
  • Giri D, Vignola ML, Gualtieri A et al. (2017). A NOVEL DENOVO FORKHEAD BOX A2 (FOXA2) MUTATION LEADS TO CONGENITAL HYPERINSULINISM, CRANIOFACIAL DYSMORPHIC FEATURES AND CONGENITAL HYPOPITUITARISM. nameOfConference

    DOI: doi

    QMRO: qmroHref
  • Rolas L, Barkaway A, Morrell S et al. (2017). Characterization of a Novel Mouse Model of Endothelial Cell Progerin Expression. nameOfConference

    DOI: doi

    QMRO: qmroHref
  • Gregory LC, Mccabe MJ, Alatzoglou KS et al. (2017). IDENTIFICATION OF GENETIC VARIANTS IN A LARGE COHORT OF PATIENTS WITH CONGENITAL HYPOTHALAMO-PITUITARY DISORDERS. nameOfConference

    DOI: doi

    QMRO: qmroHref
  • Gaston-Massuet C, McCabe MJ, Scagliotti V et al. (2016). Transcription factor 7-like 1 is involved in hypothalamo–pituitary axis development in mice and humans. nameOfConference


    QMRO: qmroHref
  • Gregory LC, Williams H, Rahman S et al. (2016). A Novel Mutation in Eukaryotic Translation Initiation Factor 2 Subunit 3 (EIF2S3) is Associated with X-Linked Hypopituitarism and Glucose Dysregulation. nameOfConference

    DOI: doi

    QMRO: qmroHref
  • Gregory L, Kypranou N, Besser R et al. (2016). The MAPK Effector BRAF is Essential for the Integrity of Hypothalamic-Pituitary Development and Deregulation of this Pathway Causes Congenital Hypopituitarism. nameOfConference

    DOI: doi

    QMRO: qmroHref
  • Avagliano L, Doi P, Tosi D et al. (2016). Cell death and cell proliferation in human spina bifida. nameOfConference


    QMRO: qmroHref
  • Fazio G, Gaston-Massuet C, Bettini LR et al. (2016). CyclinD1 Down‐Regulation and Increased Apoptosis Are Common Features of Cohesinopathies. nameOfConference


    QMRO: qmroHref
  • McCabe MJ, Hu Y, Gregory LC et al. (2015). Novel application of luciferase assay for the in vitro functional assessment of KAL1 variants in three females with septo-optic dysplasia (SOD). nameOfConference


    QMRO: qmroHref
  • Scagliotti V, Avagliano L, Gualtieri A et al. (2016). Histopathology and molecular characterisation of intrauterine-diagnosed congenital craniopharyngioma. nameOfConference


    QMRO: qmroHref
  • Gregory LC, Gaston-Massuet C, Andoniadou CL et al. (2015). The role of the sonic hedgehog signalling pathway in patients with midline defects and congenital hypopituitarism.. nameOfConference


    QMRO: qmroHref
  • Gevers EF, Gaston-Massuet C, de Roux N (2014). Pituitary and Neuroendocrinology. nameOfConference


    QMRO: qmroHref
  • Andoniadou CL, Matsushima D, Mousavy Gharavy SN et al. (2013). Sox2(+) stem/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential.. nameOfConference


    QMRO: qmroHref
  • Gevers EF, Gaston-Massuet C, Dattani MT (2013). Pituitary. nameOfConference


    QMRO: qmroHref
  • McCabe MJ, Gaston-Massuet C, Gregory LC et al. (2013). Variations in PROKR2, but not PROK2, are associated with hypopituitarism and septo-optic dysplasia.. nameOfConference


    QMRO: qmroHref
  • Graziola F, Scagliotti V, Gold-Diaz D et al. (2013). Nipbl expression analysis in the developing mouse embryo. nameOfConference

    DOI: doi

    QMRO: qmroHref
  • Jayakody SA, Andoniadou CL, Gaston-Massuet C et al. (2012). SOX2 regulates the hypothalamic-pituitary axis at multiple levels.. nameOfConference


    QMRO: qmroHref
  • Gevers EF, Gaston-Massuet C, Dattani MT (2012). Pituitary. nameOfConference


    QMRO: qmroHref
  • Andoniadou CL, Gaston-Massuet C, Reddy R et al. (2012). Identification of novel pathways involved in the pathogenesis of human adamantinomatous craniopharyngioma.. nameOfConference


  • Andoniadou CL, Signore M, Young RM et al. (2011). HESX1- and TCF3-mediated repression of Wnt/β-catenin targets is required for normal development of the anterior forebrain.. nameOfConference


    QMRO: qmroHref
  • McCabe MJ, Gaston-Massuet C, Tziaferi V et al. (2011). Novel FGF8 mutations associated with recessive holoprosencephaly, craniofacial defects, and hypothalamo-pituitary dysfunction.. nameOfConference


    QMRO: qmroHref
  • GASTON MASSUET JC, Andoniadou CL, Signore M et al. (2011). Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans.. nameOfConference


    QMRO: qmroHref
  • Jayakody SA, Andoniadou C, Signore M et al. (2011). Investigating genetic factors underlying hypopituitarism and septo-optic dysplasia in humans. nameOfConference

    DOI: doi

    QMRO: qmroHref
  • Sottocornola R, Royer C, Vives V et al. (2010). ASPP2 Binds Par-3 and Controls the Polarity and Proliferation of Neural Progenitors during CNS Development. nameOfConference


    QMRO: qmroHref
  • Gaston-Massuet C, Andoniadou CL, Signore M et al. (2010). Enhancement of the Canonical Wnt Pathway in Rathke's Pouch Results in Pituitary Tumours Reminiscent of Human Adamantinomatous Craniopharyngioma. nameOfConference

    DOI: doi

    QMRO: qmroHref
  • Gaston-Massuet C, Kelberman D, Dattani M et al. (2009). Absence of SIX3 mutations in patients with congenital hypopituitarism.. nameOfConference


    QMRO: qmroHref
  • GREENE NDE, COPP AJ, PAUWS E et al. (2009). Abstracts of papers presented at the nineteenth Genetics Society's Mammalian Genetics and Development Workshop held at the Institute of Child Health, University College London on 20 and 21 November 2008. nameOfConference


    QMRO: qmroHref
  • Andoniadou CL, Gaston-Massuet C, Martinez-Barbera JP (2009). Hesx1 antagonises canonical Wnt signalling in anterior forebrain and pituitary gland. nameOfConference


    QMRO: qmroHref
  • Jayakody SA, Gaston-Massuet C, Andoniadou CL et al. (2009). Molecular analysis of Hesx1 function in pituitary and hypothalamic development. nameOfConference


    QMRO: qmroHref
  • Massa V, Ybot-Gonzalez P, Savery D et al. (2009). Role of Zic2 in mammalian neural tube closure. nameOfConference

    DOI: doi

    QMRO: qmroHref
  • Gaston-Massuet C, Andoniadou CL, Signore M et al. (2008). Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development.. nameOfConference


    QMRO: qmroHref
  • Sajedi E, Gaston-Massuet C, Signore M et al. (2008). Analysis of mouse models carrying the I26T and R160C substitutions in the transcriptional repressor HESX1 as models for septo-optic dysplasia and hypopituitarism.. nameOfConference


    QMRO: qmroHref
  • Sajedi E, Gaston-Massuet C, Andoniadou CL et al. (2008). DNMT1 interacts with the developmental transcriptional repressor HESX1.. nameOfConference


    QMRO: qmroHref
  • ROMIO L, CASTRO S, LOPES C et al. (2007). Abstracts of papers presented at the seventeenth Genetics Society's Mammalian Genetics and Development Workshop held at the Institute of Child Health, University College London on 9 and 10 November 2006. nameOfConference


    QMRO: qmroHref
  • Ybot-Gonzalez P, Gaston-Massuet C, Girdler G et al. (2007). Neural plate morphogenesis during mouse neurulation is regulated by antagonism of Bmp signalling.. nameOfConference


    QMRO: qmroHref
  • Andoniadou CL, Signore M, Sajedi E et al. (2007). Lack of the murine homeobox gene Hesx1 leads to a posterior transformation of the anterior forebrain.. nameOfConference


    QMRO: qmroHref
  • Andoniadou C, Signore M, Sajedi E et al. (2007). Lack of the murine homeobox gene Hesx1 leads to a posterior transformation of the anterior forebrain. nameOfConference

    DOI: doi

    QMRO: qmroHref
  • Sajed E, Gaston-Massuet C, Signore M et al. (2006). Role of the homeobox gene Hesx1/HESX1 in forebrain and pituitary formation in mouse and humans. nameOfConference

    DOI: doi

    QMRO: qmroHref
  • Gaston-Massuet C, Henderson DJ, Greene NDE et al. (2005). Zic4, a zinc-finger transcription factor, is expressed in the developing mouse nervous system.. nameOfConference


    QMRO: qmroHref
  • Murdoch JN, Henderson DJ, Doudney K et al. (2003). Disruption of scribble (Scrb1) causes severe neural tube defects in the circletail mouse.. nameOfConference


    QMRO: qmroHref
  • Gaston-Massuet C, Elms P, Henderson D et al. (2003). Requirement for Zic2 during mouse neurulation.. nameOfConference

    DOI: doi

    QMRO: qmroHref

Sponsors

Collaborators

External

Internal 

Centre for Endocrinology (WHRI)

Blizard Institute

  • Professor Tim Warner

Barts Cancer Institute: Centre for Cancer and Inflammation

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

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