Dr J.p. Martinez-Barbera
I obtained my PhD at the University of Cadiz (Spain). There, I cloned and characterized several pituitary hormone genes from farmed fish species. Later, I moved to the University of Lund (Sweden) as a postdoctoral scientist in the laboratory of Stefan Krauss, where I changed field to work in developmental biology. In March 1997 I joined the laboratory of Dr. Rosa Beddington to pursue the analysis of the Hesx1 null mutant mouse I had engineered. The characterization of these mutants was instrumental for the identification of mutations in the human gene HESX1 in patients with septo-optic dysplasia. I also characterized the Hex mutants, which revealed the importance of Hex in forebrain, liver and pancreas development. Finally, I joined Prof. Antonio Simeone’ s laboratory at KCL, determined to continue my research in the field of brain development. I analyzed the brain defects in double Otx2;Gbx2 deficient mice, which demonstrated an essential role of these two transcription factors in the positioning of the mid-hindbrain boundary.
I started my own laboratory at the UCL-Institute of Child Health funded by a Research Career Development Fellowship from the Wellcome Trust in 2003. Initially, I focused my research on the cellular analysis of the forebrain defects observed in the Hesx1-deficient embryos. We generated a Hesx1-Cre mouse line to carry out detailed genetic fate mapping of Hesx1-expressing cells in the forebrain. Using this tool, we demonstrated that the absence of Hesx1 leads to a cell fate transformation of anterior to posterior forebrain. In addition, we expanded our scientific horizons by performing a thorough analysis of the pituitary defects in Hesx1 mutants.
In 2008, I was awarded a University Award from The Wellcome Trust to characterize the molecular mechanism underlying the forebrain defects observed in Hesx1-deficient mice. This award has helped to consolidate my laboratory in the field of forebrain and pituitary development. The main goal of my lab is to understand normal development of the forebrain and pituitary gland through mouse models and to apply this knowledge to reveal insights of pathological conditions affecting these structures in children. Our recent research has revealed that HESX1 normally functions by inhibiting the activation of Wnt/beta-catenin signaling in the anterior forebrain. In addition, we have demonstrated an essential role for this signaling pathway during normal pituitary development and shown that its deregulation leads to an enlargement of the pituitary progenitor/stem cell (PSC) pool and subsequently tumorigenesis. This research has revealed the molecular and cellular origin of human adamantinomatous craniopharyngioma, a devastating tumour mainly affecting children. This latter research has allowed us to generate new hypotheses regarding the biology of these elusive PSCs and discovered novel signaling pathways likely to play a role in normal pituitary development and in disease.
Another important aspect of my research at the ICH and UCL has been the establishment of an embryonic stem (ES) cell targeting and chimera production laboratory, which was not previously available. This is offered as a service within UCL and externally. We have generated more than 30 mouse models so far.
Embryonic stem cell research
Signalling pathways involved in normal pituitary development and in tumorigenesis
Transcription factors in early forebrain and pituitary development
lecturer (90 hours/year) at the University of Cadiz (Spain). I
was solely responsible for two of the courses taught in the Department of Biochemistry
and Molecular Biology: (i) ”Molecular Biology and Biotechnology (1993-1995);
(ii) Biochemistry (1996-1999). This teaching activity involved both practical
and theoretical courses. From 1996, during my post-doctoral training in Sweden,
until 1998, I went back to Spain for eight weeks each year to deliver my
lectures. Eventually, I resigned from this position in Spain in 1999, since I
was fully committed to research in UK.
Every January, I have
delivered a two-hour lecture entitled:” Axis formation in the mouse” in the BSc
course organised by Prof. Claudio Stern (Mechanisms of Development).
Prof Mehul Dattani; Dr Mike Hubank
- Andoniadou CL, Gaston-Massuet C, Reddy R, Schneider RP, Blasco MA, Le Tissier P, Jacques TS, Pevny LH, Dattani MT, Martinez-Barbera JP (2012). Identification of novel pathways involved in the pathogenesis of human adamantinomatous craniopharyngioma.. Acta Neuropathol, 124(2), 259 - 271. doi:10.1007/s00401-012-0957-9
- Sun Y, Bak B, Schoenmakers N, van Trotsenburg AS, Oostdijk W, Voshol P, Cambridge E, White JK, le Tissier P, Gharavy SN, Martinez-Barbera JP, Stokvis-Brantsma WH, Vulsma T, Kempers MJ, Persani L, Campi I, Bonomi M, Beck-Peccoz P, Zhu H, Davis TM, Hokken-Koelega AC, Del Blanco DG, Rangasami JJ, Ruivenkamp CA, Laros JF, Kriek M, Kant SG, Bosch CA, Biermasz NR, Appelman-Dijkstra NM, Corssmit EP, Hovens GC, Pereira AM, den Dunnen JT, Wade MG, Breuning MH, Hennekam RC, Chatterjee K, Dattani MT, Wit JM, Bernard DJ (2012). Loss-of-function mutations in IGSF1 cause an X-linked syndrome of central hypothyroidism and testicular enlargement.. Nat Genet, 44(12), 1375 - 1381. doi:10.1038/ng.2453
- Jayakody SA, Andoniadou CL, Gaston-Massuet C, Signore M, Cariboni A, Bouloux PM, Le Tissier P, Pevny LH, Dattani MT, Martinez-Barbera JP (2012). SOX2 regulates the hypothalamic-pituitary axis at multiple levels.. J Clin Invest, 122(10), 3635 - 3646. doi:10.1172/JCI64311
- Reynaud R, Jayakody SA, Monnier C, Saveanu A, Bouligand J, Guedj AM, Simonin G, Lecomte P, Barlier A, Rondard P, Martinez-Barbera JP, Guiochon-Mantel A, Brue T (2012). PROKR2 variants in multiple hypopituitarism with pituitary stalk interruption.. J Clin Endocrinol Metab, 97(6), E1068 - E1073. doi:10.1210/jc.2011-3056
- West EL, Gonzalez-Cordero A, Hippert C, Osakada F, Martinez-Barbera JP, Pearson RA, Sowden JC, Takahashi M, Ali RR (2012). Defining the integration capacity of embryonic stem cell-derived photoreceptor precursors.. Stem Cells, 30(7), 1424 - 1435. doi:10.1002/stem.1123
- McCabe MJ, Gaston-Massuet C, Tziaferi V, Gregory LC, Alatzoglou KS, Signore M, Puelles E, Gerrelli D, Farooqi IS, Raza J, Walker J, Kavanaugh SI, Tsai PS, Pitteloud N, Martinez-Barbera JP, Dattani MT (2011). Novel FGF8 mutations associated with recessive holoprosencephaly, craniofacial defects, and hypothalamo-pituitary dysfunction.. J Clin Endocrinol Metab, 96(10), E1709 - E1718. doi:10.1210/jc.2011-0454
- Gaston-Massuet C, Andoniadou CL, Signore M, Jayakody SA, Charolidi N, Kyeyune R, Vernay B, Jacques TS, Taketo MM, Le Tissier P, Dattani MT, Martinez-Barbera JP (2011). Increased Wingless (Wnt) signaling in pituitary progenitor/stem cells gives rise to pituitary tumors in mice and humans.. Proc Natl Acad Sci U S A, 108(28), 11482 - 11487. doi:10.1073/pnas.1101553108
- Alatzoglou KS, Andoniadou CL, Kelberman D, Buchanan CR, Crolla J, Arriazu MC, Roubicek M, Moncet D, Martinez-Barbera JP, Dattani MT (2011). SOX2 haploinsufficiency is associated with slow progressing hypothalamo-pituitary tumours.. Hum Mutat, 32(12), 1376 - 1380. doi:10.1002/humu.21606
- McCabe MJ, Gaston-Massuet C, Tziaferi V, Gregory LC, Alatzoglou KS, Signore M, Puelles E, Gerrelli D, Farooqi IS, Raza J, Walker J, Kavanaugh SI, Tsai PS, Pitteloud N, Martinez-Barbera JP, Dattani MT (2011). Novel FGF8 Mutations Associated with Recessive Holoprosencephaly, Craniofacial Defects, and Hypothalamo-Pituitary Dysfunction. J CLIN ENDOCR METAB, 96(10), E1709 - E1718. doi:10.1210/jc.2011-0454
- Norris FC, Cleary JO, Modat M, Sinclair B, Mccue K, Wells JA, Martinez-Barbera JP, Brander S, Fisher E, Scambler PJ, Ourselin S, Lythgoe MF (2011). Mouse phenotyping using high resolution 3D microscopic magnetic resonance imaging.
- Jayakody SA, Andoniadou C, Signore M, Gaston-Massuet C, Pevny LH, Brue T, Martinez-Barbera J-P (2011). Investigating genetic factors underlying hypopituitarism and septo-optic dysplasia in humans.
- Dattani MT, Martinez-Barbera JP (2011). The future of genomic endocrinology.. Front Endocrinol (Lausanne), 2, 11 - . doi:10.3389/fendo.2011.00011
- Andoniadou CL, Signore M, Young RM, Gaston-Massuet C, Wilson SW, Fuchs E, Martinez-Barbera JP (2011). HESX1- and TCF3-mediated repression of Wnt/β-catenin targets is required for normal development of the anterior forebrain.. Development, 138(22), 4931 - 4942. doi:10.1242/dev.066597
- Cleary JO, Modat M, Norris FC, Price AN, Jayakody SA, Martinez-Barbera JP, Greene ND, Hawkes DJ, Ordidge RJ, Scambler PJ, Ourselin S, Lythgoe MF (2011). Magnetic resonance virtual histology for embryos: 3D atlases for automated high-throughput phenotyping.. Neuroimage, 54(2), 769 - 778. doi:10.1016/j.neuroimage.2010.07.039
- Pauws E, Hoshino A, Bentley L, Prajapati S, Keller C, Hammond P, Martinez-Barbera JP, Moore GE, Stanier P (2010). Tbx22(null) mice have a submucous cleft palate due to reduced palatal bone formation and also display ankyloglossia and choanal atresia phenotypes (vol 18, pg 4171, 2009). HUM MOL GENET, 19(15), 3103 - 3103. doi:10.1093/hmg/ddq223
- Gaston-Massuet C, Andoniadou CL, Signore M, Jayakody S, Charolidi N, Le Tissier P, Dattani M, Martinez-Barbera JP (2010). Enhancement of the Canonical Wnt Pathway in Rathke's Pouch Results in Pituitary Tumours Reminiscent of Human Adamantinomatous Craniopharyngioma.
- McCabe MJ, Tziaferi V, Gaston-Massuet C, Gregory LC, Walker J, Tsai PS, Pitteloud N, Martinez-Barbera JP, Dattani MT (2010). Mutations in the Gene Encoding Fibroblast Growth Factor 8, FGF8, Are Associated with Complex Midline and Hypothalamo-Pituitary Defects..
- Pauws E, Hoshino A, Bentley L, Prajapati S, Keller C, Hammond P, Martinez-Barbera J-P, Moore GE, Stanier P (2009). Tbx22null mice have a submucous cleft palate due to reduced palatal bone formation and also display ankyloglossia and choanal atresia phenotypes. Human Molecular Genetics, 18(21), 4171 - 4179.
- de Melo IS, Iglesias C, itez-Rondan A, Medina F, Martinez-Barbera JP, Bolivar J (2009). NOA36/ZNF330 is a conserved cystein-rich protein with proapoptotic activity in human cells. Biochimica et Biophysica Acta-Molecular Cell Research, 1793(12), 1876 - 1885.
- Andoniadou CL, Gaston-Massuet C, Martinez-Barbera JP (2009). Hesx1 antagonises canonical Wnt signalling in anterior forebrain and pituitary gland. Mechanisms of Development, 126, S229 - S230.
- Charolidi N, Cynthia LA, Signore M, Richard GJ, Martinez-Barbera JP (2009). Developmental regulatory targets of the homeobox transcription factor HESX1. Mechanisms of Development, 126, S117 - S117.
- Gaston-Massuet C, Kelberman D, Dattani M, Martinez-Barbera JP (2009). Absence of SIX3 mutations in patients with congenital hypopituitarism. Am J Med Genet A, 149A(12), 2874 - 2876. doi:10.1002/ajmg.a.33103
- Pauws E, Hoshino A, Bentley L, Prajapati S, Keller C, Martinez-Barbera JP, Moore GE, Stanier P (2009). Loss of Tbx22 causes submucous cleft palate, ankyloglossia and choanal atresia.
- Longbottom R, Fruttiger M, Douglas RH, Martinez-Barbera JP, Greenwood J, Moss SE (2009). Genetic ablation of retinal pigment epithelial cells reveals the adaptive response of the epithelium and impact on photoreceptors.. Proc Natl Acad Sci U S A, 106(44), 18728 - 18733. doi:10.1073/pnas.0902593106
- Sajedi E, Gaston-Massuet C, Signore M, Andoniadou CL, Kelberman D, Castro S, Etchevers HC, Gerelli D, Dattani MT, Martinez-Barbera JP (2008). Analysis of mouse models carrying the I26T and R160C substitutions in the transcriptional repressor HESX1 as models for septo-optic dysplasia and hypopituitarism. Disease Models and Mechanisms, 1(4-5), 241 - 254. doi:10.1242/dmm.00071
- Abrahamsen B, Zhao J, Asante CO, Cendan CM, Marsh S, Martinez-Barbera JP, Nassar MA, Dickenson AH, Wood JN (2008). The cell and molecular basis of mechanical, cold, and inflammatory pain. Science, 321(5889), 702 - 705.
- Sajedi E, Gaston-Massuet C, Signore M, Andoniadou CL, Kelberman D, Castro S, Etchevers HC, Gerrelli D, Dattani MT, Martinez-Barbera JP (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(4-5), 241 - 254. doi:10.1242/dmm.000711
- Gaston-Massuet C, Andoniadou CL, Signore M, Sajedi E, Bird S, Turner JMAAM-B, J P (2008). Genetic interaction between the homeobox transcription factors HESX1 and SIX3 is required for normal pituitary development. Developmental Biology, , - . doi:10.1016/j.ydbio.2008.08.008
- Sajedi E, Gaston-Massuet C, Andoniadou CL, Signore M, Hurd PJ, Dattani M, Martinez-Barbera JP (2008). DNMT1 interacts with the developmental transcriptional repressor HESX1. Biochim.Biophys.Acta, 1783(1), 131 - 143. doi:10.1016/j.bbamcr.2007.08.010
- Kelberman D, de Castro SC, Huang S, Crolla JA, Palmer R, Gregory JW, Taylor D, Cavallo L, Faienza MF, Fischetto R, Achermann JC, Martinez-Barbera JP, Rizzoti K, Lovell-Badge R, Robinson IC, Gerrelli D, Dattani MT (2008). SOX2 plays a critical role in the pituitary, forebrain, and eye during human embryonic development. J Clin Endocrinol Metab, 93(5), 1865 - 1873. doi:10.1210/jc.2007-2337
- Andoniadou CL, Signore M, Sajedi E, Gaston-Massuet C, Kelberman D, Burns AJ, Itasaki N, Dattani M, Martinez-Barbera JP (2007). Lack of the murine homeobox gene Hesx1 leads to a posterior transformation of the anterior forebrain. Development, 134(8), 1499 - 1508. doi:10.1242/dev.02829
- Val P, Martinez-Barbera JP, Swain A (2007). Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage. Development, 134(12), 2349 - 2358.
- Withington SL, Scott AN, Saunders DN, Lopes Floro K, Preis JL, Michalicek J, Maclean K, Sparrow DB, Martinez-Barbera JPAD, S L (2006). Loss of Cited2 affects trophoblast formation and vascularization of the mouse placenta. Developmental Biology, 294, 67 - 82.
- Sajed E, Gaston-Massuet C, Signore M, Dattani M, Martinez-Barbera JP (2006). Role of the homeobox gene Hesx1/HESX1 in forebrain and pituitary formation in mouse and humans.
- Bort R, Signore M, Tremblay K, Martinez-Barbera JPAZ, K S (2006). ). Hex homeobox gene controls the transition of the endoderm to a pseudostratified, cell emergent epithelium for liver bud development. Developmental Biology, 290, 44 - 56.
- Signore M, Sajedi S, Gaston-Massuet C, Dattani M, Martinez-Barbera JP (2005). Role of the Homeobox Gene Hesx1 in forebrain and pituitary formation in mouse and human. MECH DEVELOP, 122, S33 - S33.
- Woods KS, Cundall M, Turton J, Rizotti K, Mehta A, Palmer R, Wong J, Chong WK, Al-Zyoud M, El-Ali M, Otonkoski T, Martinez-Barbera JP, Thomas PQ, Robinson IC, Lovell-Badge R, Woodward KJ, Dattani MT (2005). Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism. Am J Hum Genet, 76(5), 833 - 849. doi:10.1086/430134
- Ivanova A, Signore M, Caro N, Greene ND, Copp AJ, Martinez-Barbera JP (2005). In vivo genetic ablation by Cre-mediated expression of diphtheria toxin fragment A. Genesis, 43(3), 129 - 135.
- Weninger WJ, Floro KL, Bennett MB, Withington SL, Preis JI, Barbera JPM, Mohun TJ, Dunwoodie SL (2005). Cited2 is required both for heart morphogenesis and establishment of the left-right axis in mouse development. Development, 132(6), 1337 - 1348.
- Ragge NK, Brown AG, Poloschek CM, Lorenz B, Henderson RA, Clarke MP, Russell-Eggitt I, Fielder A, Gerrelli D, Martinez-Barbera JP, Ruddle P, Hurst J, Collin JR, Salt A, Cooper ST, Thompson PJ, Sisodiya SM, Williamson KA, Fitzpatrick DR, van Heyningen V, Hanson IM (2005). Heterozygous mutations of OTX2 cause severe ocular malformations.. The American Journal of Human Genetics, 76(6), 1008 - 1022. doi:10.1086/430721
- Bort R, Martinez-Barbera JP, Beddington RS, Zaret KS (2004). Hex homeobox gene-dependent tissue positioning is required for organogenesis of the ventral pancreas. Development, (131), 797 - 806.
- Rana R, Martinez-Barbera JP, Rodriguez TA, Lynch D, Hirst E, Smith JC, Beddington RSP (2004). Targeted deletion of the novel cytopalsmic dyelinmD2LIC disrupts the embryonic organiser, formation of the body axes and specification of ventral cell fates. Development, (131), 4999 - 5007.
- Guo Y, Chan R, Ramsey H, Li W, Xie X, Shelley WC, Martinez-Barbera JP, Bort B, Zaret K, Yoder MAH, R (2003). The homeoprotein Hex is required for hemangioblast differentiation.. Blood, 102(2428), 2435 - .
- Guo Y, Chan R, Ramsey H, Li W, Xie X, Shelley WC, Martinez-Barbera JP, Bort B, Zaret K, Yoder M, Hromas R (2003). The homeoprotein Hex is required for hemangioblast differentiation.. Blood, 102(7), 2428 - 2435. doi:10.1182/blood-2003-02-0634
- Gogoi RN, Schubert FR, Martinez-Barbera JP, Acampora D, Simeone A, Lumsden A (2002). The pair-type homeobox gene Dmbx1marks the midbrain and pretectum. Mechanisms of Development, 114, 213 - 217.
- Dattani ML, Martinez-Barbera J, Thomas PQ, Brickman JM, Gupta R, Wales JK, Hindmarsh PC, Beddington RS, Robinson IC (2000). Molecular genetics of septo-optic dysplasia. Horm Res, 53 Suppl 1, 26 - 33.
- Dattani MT, Martinez-Barbera JP, Thomas PQ, Brickman JM, Gupta R, Martensson IL, Toresson H, Fox M, Wales JK, Hindmarsh PC, Krauss S, Beddington RS, Robinson IC (1998). Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse. Nat Genet, 19(2), 125 - 133. doi:10.1038/477
- Martínez-Barberá JP, Vila V, Valdivia MM, Castrillo JL (1997). Molecular cloning of gilthead seabream (Sparus aurata) pituitary transcription factor GHF-1/Pit-1.. Gene, 185(1), 87 - 93.