The Waltz laboratory is interested in the molecular mechanisms by which cell-surface receptor tyrosine kinases and growth factors control human disease processes, with a special emphasis on mechanisms regulating cancer growth and metastasis, and inflammation. The Waltz group has made several seminal discoveries related to the Ron receptor tyrosine kinase in both breast and prostate cancers. In particular, the laboratory has shown that Ron overexpression specific to the breast epithelium is sufficient to induce aggressive breast cancers that are highly metastatic. In addition, the Waltz group has found that Ron is an important contributing factor controlling the growth of prostate cancers through the regulation of tumor angiogenesis (blood vessel formation). The immediate goals for these projects are to understand the physiological signaling pathways that control the aggressive tumor phenotype downstream of Ron signaling. Future studies will involve the utilization of in vivo gene-targeted murine models to study disease progression as well as the isolation and analysis of primary epithelial and stromal cells from the breast and prostate environments. In addition, the laboratory plans to use orthotopic transplantation of gene-modified cell lines into syngeneic models to explore these signaling pathways in detail.
With respect to control of cellular inflammation, the Waltz laboratory has also shown that Ron is expressed on select macrophage populations, and that signaling through this receptor negatively regulates the balance of cytokine and chemokine production during acute tissue injury in vivo. This critical balance of immune mediators is essential to control the body's response to injury, wounding, and infection. To analyze the mechanisms responsible for the Ron-dependent regulation of cytokine/chemokine production, the laboratory utilizes co-culture systems composed of primary tissue macrophages and epithelial cells from select gene knockout animals to dissect the role of macrophages in tissue injury.
The overall goal of the Waltz laboratory is to examine the Ron signaling pathway as a novel therapeutic target in the regulation of a variety of human diseases.