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People About the institute María Dominguez Castellano
1988 B. Sci in Biochemistry, Universidad de Sevilla, Spain

Ph.D program:
1993 Ph.D. in Developmental Biology  at Center of Molecular Biology Severo Ochoa (CBMSO) at the Universidad Autónoma de Madrid, Spain

Posdoctoral Positions:
Jan 1997-Dec 1999 Independent postdoctoral at the MRC-LMB, Cambridge, UK
Sept 1993- Dec 1996  Postdoctoral Fellow, University of Zurich, Zurich, Switzerland
April 1993-Aug 1993 Postdoctoral at the CBMSO, CSIC_UMH, Madrid, Spain

Previous positions:
2005-2008  Researcher of CSIC, Instituto de Neurociencias, CSIC-UMH, Alicante, Spain
2002-2005  Vice-Director, Instituto de Neurociencias, CSIC-UMH, Alicante, Spain
2000-2005  Tenured Scientist of CSIC, Instituto de Neurociencias, CSIC-UMH, Alicante, Spain
Jan 2000-July 2000 Interim Scientist of CSIC, Instituto de Neurociencias, CSIC-UMH, Alicante, Spain

Current Position:
2016-Present Director of the Department of Developmental Neurobiology, Instituto de Neurociencias, CSIC-UMH, Alicante, Spain
2008-Present  Full Professor of CSIC, Instituto de Neurociencias, CSIC-UMH, Alicante, Spain
2016-Present Member of the Board of Directors, , Instituto de Neurociencias, CSIC-UMH, Alicante, Spain
2016-Present Member of the Board of Director of Severo Ochoa Excellence Grant
2018-Alternate representative of institutes and centres of research of the Valencia Government for the Advisory Council of Patronage (CASMEC)
2007-Present Member of European Molecular Biology Organization (EMBO)
2012-2014 Executive member of the Spanish Society of Genetics
2004-2006 Member of the Advisory Board of the Area of Biology and Biomedicine of CSIC
2016- Editorial Board member of Cell Stress, Cellular Signalling

Research Fields:
The main questions we studied are what and how regulate growth of an organ and between organs, and how does disruption of these regulations lead to cancer. Our work uses the fruit fly, Drosophila melanogaster as experimental system. The control of growth is remarkably precise. Think, for example, of how a human face, or the wings of an insect, are perfectly matched in size and shape, even though each part grows separately. This precision is even more striking when considering the noisiness of gene expression and perturbations due to environmental stress, errors, and mutations. The degree of bilateral symmetry or asymmetry of an individual reflects such vulnerability of development and growth processes but mechanisms exist that can buffer such  variation. Our lab discovered that developmental buffering involves organ-organ communication mediated by a hormone of the relaxin family (Dilp8). More recently we also uncovered the receptor of such hormone, Lgr3. In the absence of the hormone or by silencing its receptor in the brain, flies cannot keep tight control of size and display bilateral asymmetry similar to some asymmetric growth syndrome in humans. Cell-cell and organ-organ communication is also essential in the formation and progression of cancer. The Notch pathway is one of such important cell-cell communication network in both normal physiology and cancer. Using unbiased genetic and drug screens, we have uncovered conserved cooperative events in tumorigenesis and new therapies for targeting Notch-driven cancer including already approved anti-inflammatory drugs. We further use the adult intestine and the stem cell biology to study organ plasticity and homeostasis. Major findings in this area are that intestinal stem and progenitor cell number and differentiation involves a mesenchymal-epithelial transition and basal caspase activity, and the identification of remote control of stem cell activity by brain-derived hormones.

Representative Publications

Gutierrez-Perez, I. , Jordan-Rowley, J., Lyu, X., Valadez-Graham, V., Vallejo, D.M., Ballesta-Illan, E., Lopez-Atalaya, J.P., Kremsky, I., Caparros, E., Corce, V.G., Dominguez, M " Ecdysone-Induced 3D Chromatin Reorganization Involves Active Enhancers Bound by Pipsqueak and Polycomb. " Cell Rep . 28(10) , 2715 - 2727.e5 ( 2019 )

Reiff, T. , Antonello, Z.A., Ballesta-Illán, E., Mira, L., Sala, S., Navarro, M., Martinez, L.M., Dominguez, M " Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila. " EMBO J . 4 , 38(21) - e101346 ( 2019 )

Villegas, S.N , Gombos, R., García-López, L., Gutiérrez-Pérez, I., García-Castillo, J., Vallejo, D.M., Da Ros, V., Ballesta-Illán, E., Mihály, J., Dominguez, M. " PI3K/Akt Cooperates with Oncogenic Notch by Inducing Nitric Oxide-Dependent Inflammation. " Cell Rep . 22(10) , 2541 - 2549 ( 2018 )

Vallejo DM. , Juarez-Carreño S., Bolivar J., Morante J., Dominguez M. " A brain circuit that synchronizes growth and maturation revealed through Dilp8 binding to Lgr3. " Science . 350(6262) , - aac6767 ( 2015 )

Garelli, A , Gontijo, A,, Miguela, V,, Caparros, E,, Dominguez, M " Imaginal discs secrete insulin-like peptide 8 to mediate plasticity of growth and maturation time. " Science . 336(6081) , 579 - 582 ( 2012 )
Consejo Superior de Investigaciones Científicas
Universidad Miguel Hernández

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