Mechanisms of growth control and cancer

Lines of investigation

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

Body-fat sensor triggers ribosome maturation in the steroidogenic gland to initiate sexual maturation in Drosophila Juarez-Carreño S, Vallejo DM, Carranza-Valencia J, Palomino-Schätzlein M, Ramon-Cañellas P, Santoro R, de Hartog E, Ferres-Marco D, Romero A, Peterson HP, Ballesta-Illan E, Pineda-Lucena A, Dominguez M, Morante J Cell Rep 2021 37(2):109830 https://doi.org/10.1016/j.celrep.2021.109830
Ecdysone-Induced 3D Chromatin Reorganization Involves Active Enhancers Bound by Pipsqueak and Polycomb Gutierrez-Perez I, Rowley MJ, Lyu X, Valadez-Graham V, Vallejo DM, Ballesta-Illan E, Lopez-Atalaya JP, Kremsky I, Caparros E, Corces VG, Dominguez M Cell Rep 2019 28(10):2715 https://doi.org/10.1016/j.celrep.2019.07.096
Notch and EGFR regulate apoptosis in progenitor cells to ensure gut homeostasis in Drosophila Reiff T, Antonello ZA, Ballesta-Illán E, Mira L, Sala S, Navarro M, Martinez LM, Dominguez M EMBO Journal 2019 38(21):e101346 https://doi.org/10.15252/embj.2018101346
PI3K/Akt Cooperates with Oncogenic Notch by Inducing Nitric Oxide-Dependent Inflammation Villegas SN, Gombos R, Garcia-Lopez L, Gutierrez-Perez I, Garcia-Castillo J, Vallejo DM, Da Ros VG, Ballesta-Illan E, Mihaly J, Dominguez M Cell Rep 2018 22(10):2541 https://doi.org/10.1016/j.celrep.2018.02.049
A brain circuit that synchronizes growth and maturation revealed through Dilp8 binding to Lgr3 Vallejo DM, Juarez-Carreño S, Bolivar J, Morante J, Dominguez M Science 2015 350(6262):aac6767 https://doi.org/10.1126/science.aac6767

See all

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Main Investigator