Injured or stressed tissues produce a small protein signal called platelet-derived growth factor (PDGF). Some cells have specific PDGF-receptors on the cell surface that allow them to sense the protein signal. PDGF stimulates wound repair, but too much promotes fibrosis. Therefore, our bodies must maintain a careful balance to achieve proper tissue repair.

A few cells in the body, called adult stem cells, have great potential to regenerate damaged tissue and influence neighboring cells to support wound repair. Some kinds of adult stem cells have PDGF-receptors. We are still uncovering how PDGF-receptors control adult stem cells, and how aberrant PDGF signaling could promote disease through misregulation of adult stem cells. We focus on a few tissues that are rich in adult stem cells and PDGF: blood vessels, skin, fat, and skeleton. The tissue repair process appears to be similar in mice and humans, in most respects. We use genetically engineered mice with different amounts of PDGF to understand how PDGF might be acting in tissue repair. We can also mark adult stem cells while they are still in the tissue and track their behavior during tissue repair, an approach called lineage tracing. By understanding how tissue repair is regulated by PDGF and adult stem cells, we hope to suggest new therapies for tissue repair and protection from fibrosis.

We are also studying human genetic diseases where hyperactive PDGFR signaling causes connective tissue overgrowth or wasting, depending on cell types and signaling pathways that are still being identified. We also seek to understand the function of mesenchymal progenitor cells that reside in niches around blood vessels throughout the body, and that express combinations of the two vertebrate PDGFRs, PDGFRα and PDGFRβ.