Doble LabStem Cell Research

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.

Pluripotent Stem Cells

There are several types of stem cells, and some have different potencies that determine the number of unique cell types they can generate. Pluripotent stem cells, which include embryonic stem cells derived from microscopic embryos, can give rise to all cell types found in an adult organism. The Doble lab uses mouse embryonic stem cells and human induced pluripotent stem cells for most of its studies.

Model Systems

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.

Five Methods Used in the Doble Lab


Cellular differentiation on micropatterned surfaces

By confining pluripotent cells to micropatterns of different shapes, we can generate highly reproducible differentiation environments that allow us to study detailed mechanisms of cell fate determination. The beautiful image on the left is a single micropatterned circle filled with differentiating embryonic stem cells expressing three different fluorescent fusion proteins. The diameter of the unmagnified circle is 1 mm.


RNA-seq, ChIP-seq and ATAC-seq

Several projects in the lab are related to understanding the mechanisms through which transcriptions factors of the TCF/LEF family regulate target genes. These transcription factors are the primary mediators of Wnt-regulated transcriptional programs. We employ next-generation sequencing approaches that enable us to evaluate genome-wide consequences of transcription factor activation or repression.


In vitro differentiation: gastruloids, embryoid bodies and directed differentiation

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.

Research Projects

The Doble lab relocated to Winnipeg at the beginning of July 2019 (see our Blog for details). You can find out a bit more about projects we are working onby clicking the Learn More button below. Learn about current and past lab members by clicking the Lab Members button.