My work as a CIRM bridges scholar focuses on the intestinal stem cell (ISC) niche. The surfaces of the intestine and colon are covered in a highly regenerative epithelial layer, which rapidly renews itself in response to mechanical and chemical damage. This renewal is affected by a stem cell population that resides in small invaginations of the intestine known as crypts. Crypt base cells presenting the g-protein couple receptor Lgr5 are thought to represent the actively cycling stem cells and have been shown to repopulate the intestinal epithelium in a clonal manner. The proliferation of these cells is tightly regulated by growth factors released by adjacent paneth cells and the sub-epithelial compartment, such as WNT and bone morphogenetic protein ligands. Previous transcriptome analysis of FACS sorted Lgr5+ cells has revealed a number of transcripts present at higher levels compared to the surrounding tissue. I focus on the protein product of one of these upregulated genes; Repulsive Guidance Molecule B (RGMb). RGMb is a GPI-linked cell surface protein that is known to act as a BMP co-receptor in conjunction with BMP type 1 receptors and another receptor known as Neogenin. Thus far I have generated adenoviruses that can infect mice and express the extracellular domains of these receptors in their blood plasma, allowing me to investigate the role of this molecule by observing changes in intestinal stem cell dynamics through histology and antibody staining. I’m generating siRNA reagents that will allow me to knockdown RGMb transcripts in organotypic culture in-vitro­ and also plan to purify the ectodomains of RGMb and Neogenin for use in-vitro. Ultimately I would like to know if RGMb is playing a role as a BMP co-receptor in Lgr5+ ISCs and whether or not it’s essential for maintenance of a functional ISC niche.