Our laboratory is interested in understanding how the intestinal stem cell and its surrounding niche is regulated in the context of development and disease. We have taken several approaches to dissect this important questions:
Project Summaries Bold text
The implication of circulating bone marrow-derived stem cells and cell fusion on intestinal tissue regeneration and tumorigenesis
Our laboratory has shown that circulating BMDCs fuse with intestinal stem cells upon tissue injury, inclusive of intestinal inflammatory disease and intestinal carcinogenesis. We now extend these studies to identify the cellular mediators of fusion, the underlying mechanism, and the long-term fate to the cell fusion hybrids. Our studies offer an exciting alternative view of how tissue regenerates and have the potential to explain how chronic injury can lead to intestinal tumorigenesis. Role of Wnt signaling in regulating the intestinal stem cell niche
Temporal manipulation of the Wnt/β-catenin mediated signaling pathway using genetically engineered mice and of the non-canonical Wnt signaling pathway using lentiviral mediated delivery will facilitate an understanding of how the intestinal stem cell niche is regulated during development and disease.
Identification of markers for intestinal stem cells and intestinal cancer stem cells
The cancer stem cell theory for why many cancers recur after treatment presents a novel target for cancer therapeutics. However, the notion that cancer stem cells arise from mutations in tissue stem cells suggests that these two cell populations may share similar features and targetable epitopes. We have taken a systematic approach to defining surface antigens on these two populations by generating novel monoclonal antibodies. Our studies will establish a link between these two populations and may provide novel epitopes that are unique to the cancer stem cell that can be used for targeted therapy.
We work in Portland, Oregon at OHSU, in the Department of Dermatology and the OHSU Knight Cancer Institute.