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    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 can give rise to all cell types found in an adult organism. The Doble lab uses mouse embryonic stem cells, a type of pluripotent stem cell, for many of its studies.

    Model Systems

    Our primary model systems employ mouse embryonic stem cells that we manipulate using methods described in the sections below.

    Five Methods Used in the Doble Lab

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    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.

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    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.

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    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.

    Research Projects

    The Doble lab relocated to Winnipeg at the beginning of July 2019 (see our Blog for details). Many projects are on hold until new trainees are recruited, although key studies are ongoing. You can find out more about projects we are working on and ones that remain for new recruits to pursue by clicking the Learn More button below.