Mechanisms of growth control and cancer

The main questions we studied are how growth is regulated at the organ, between organs, and at the organism level, and how the disruption of these regulations leads to cancer. We leverage the powerful genetic tools in the fruit fly, Drosophila melanogaster, to address these questions. The precision and robustness of such growth control are illustrated by bilateral symmetry. 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 striking when considering the noisiness of gene expression, unavoidable environmental perturbations, errors, and mutations. We have found that an individual’s degree of bilateral symmetry or asymmetry reflects the vulnerability of development and growth processes to such perturbations and the shortage of mechanisms that buffer such variation. Our lab discovered that developmental buffering involves organ-organ and organ-brain communication mediated by a hormone of the relaxin family (Ilp8) and its receptor Lgr3 expressed in the CNS. In addition, to the high-order control of growth, cell-cell communication and cancer cell-host communication are important in both the prevention and initiation and progression of cancer. This communication is mediated by hormones and signaling pathways such as the Notch, PI3K/AKT/PTEN, and JAK/SAT pathways. The main findings in this area are the demonstration that in response to fat levels, a neuroendocrine axis is activated and matures that activates sexual maturation in the fly Drosophila melanogaster and that this axis causes obesity when inactive, but can be rescued with the hormone human Leptin, demonstrating conservation of processes. Furthermore, we have reported that hormones produced by the brain can remodel the size of adult organs such as the gut to sustain the high energetic demands of reproduction.