Harvard Catalyst Profiles

Multiple hormones produced in the intestine can control appetite, making them excellent targets for obesity therapies. However, the cells that make these hormones (enteroendocrine (EE) cells) are rare, and there is a lack of understanding around what controls their differentiation and production of certain hormones. Our lab (I work in David Breault's lab) is focused on trying to understand the molecular mechanisms that drive human intestinal stem cells to become EE cells, and what drives the production and secretion of specific hormones. By doing this, we hope to elucidate druggable targets for future obesity-specific therapies. The majority of our studies use primary human intestinal stem cells grown in vitro using the 3D-organoid system to model the functional intestine. Aside from tissue culture, we also do quantitative PCR, immunofluorescence staining, flow cytometry, and ELISAs. Prior lab experience is helpful but not necessary. We currently have multiple ongoing studies, looking at different aspects of the EE lineage, any of which a student could work on (from understanding what drives a stem cell to differentiate to what causes an EE cell to produce and secrete a hormone). We also have some large datasets a student could look through to identify a new transcriptional target to analyze.