The Camargo lab studies how tumor growth is inhibited in a tissue-wide context. The lab’s hypothesis is that the same intrinsic mechanisms that regulate organs to reach an appropriate size in their own environment may normally act as tumor suppressors. Using a mouse model, Camargo’s team is determining whether mechanisms controlling tissue size act as critical regulators of tumor growth and have focused their studies on the Hippo pathway of genes to test this model. Using a range of molecular biological techniques and RNA interference (RNAi) screens, they hope to identify novel regulators of a signaling pathway, known as the Hippo pathway, and to then determine their role as tumor suppressor genes.
As an Innovation Fund investigator, Camargo’s lab is collaborating with the lab of Alexander A. Gimelbrant, Ph.D., to combine an expertise in developmental biology and epigenetics to study mechanisms behind clonal epigenetic mosaicism. Individuals who are genetically identical can have dramatically different physical features or manifestations, known as phenotypes. Similarly, cells may exhibit significant phenotypic variation despite being genetically identical, or clones. Mechanisms behind such variations are poorly understood, but could be caused by epigenetics, or modifications to DNA that do not affect the sequence but do alter gene expression. For instance, although animals inherit two copies of each gene, one from each parent, in certain instances either the maternal or paternal gene is silenced. This phenomenon is random and results in a mosaic in which some cells express genes of maternal origin and others express genes of paternal origin. This diversity can lead to differences in cellular behavior and overall phenotype. For instance, variations among immune cells can affect how they respond to infection or chemotherapy. Together, Gimelbrant and Camargo will utilize mouse models and cutting-edge tools like cellular barcoding and single-cell RNA-seq to study mechanisms behind epigenetic clone-to-clone variation, or clonal epigenetic mosaicism. This work could shed light on how non-genetic variations drive cell response during injury, infection, or therapeutic interventions.