The Doble lab studies the signaling networks within stem cells that control their amazing properties. We are especially interested in key developmental signaling pathways essential for stem cell self-renewal and differentiation. Malfunctions in these pathways underlie many human diseases including numerous cancers and developmental disorders.
Our primary model systems employ pluripotent stem cells that we manipulate using methods described in the sections below. We are also studying cellular models of the Wnt subgroup of a type of childhood brain cancer called medulloblastoma. We grow Wnt-activated medulloblastoma cells from mouse tumours as tumour spheres in culture. Wnt-activated medulloblastoma is very rare, and human model systems are lacking. We are developing human Wnt-activated cell model systems from induced pluripotent stem cells.
We use a variety of techniques to assess the ability of pluripotent stem cells to differentiate and self-renew. One striking example is the formation of embryoid bodies, which spontaneously generate cardiomyocytes that you can observe contracting in the video. By using different growth factors and culture conditions, we can differentiate human induced pluripotent stem cells into any cell or tissue type we are interested in studying.