Dr Rebecca Keough

Research Interests

Embryonic Stem Cell Laboratory
Pluripotent Stem Cells
Pluripotent stem cells, such as embryonic stem (ES) cells and induced pluripotent (iPS) cells, have the ability to differentiate into all of the cell types of the body. This remarkable cell fate plasticity, together with the ability to grow and maintain large numbers of pluripotent cells in culture, provides a potentially valuable and ready source of cells that can, in theory, be differentiated to any cell type for the treatment of trauma (e.g. spinal cord injury) and disease (e.g. type I diabetes, Parkinsons Disease etc). Understanding how to efficiently grow and maintain pluripotent cells and how to precisely direct cell differentiation to form pure populations of specific cells with useful therapeutic value are key challenges in this field. Current research in our lab is focused on:

1.      Understanding the molecular mechanisms that regulate pluripotency: at the level of signal transduction, gene expression and epigenetics.
2.      Understanding the molecular determinants of cell fate choice as the pluripotent cell differentiates. 

Early mammalian development
Embryonic stem cells are derived from the pre-implantation mammalian embryo. At this early stage, the embryo is called a blastocyst and consists of 2 distinct cell types: the trophectoderm, which goes on to form the extra-embryonic placental structures, and the pluripotent inner cell mass (ICM), from which the embryo itself derives. Subsequent differentiation of the ICM produces a second pluripotent cell population, primitive ectoderm, that then differentiates (via the process of gastrulation) to form the 3 germ layers, mesoderm, endoderm and ectoderm, that give rise to the different tissues and organs of the body. These processes, and subsequent embryonic development, are tightly regulated. The signals and genes that control cell fate and developmental outcomes during the early stages of development are not yet completely understood. However, genetic mutations or environmental factors such as drugs, chemicals, radiation etc, can result in alterations in these pathways that result in developmental defects and disease. ES Cells as a Model for Mammalian Development A unique in vitro model of mammalian embryogenesis was developed at the University of Adelaide by the Rathjen Laboratory (now at the University of Melbourne). This model is based around the formation of early primitive ectoderm-like (EPL) cells from mouse ES cells. This second pluripotent cell type can then be manipulated to differentiate to either an ectodermal or mesendodermal cell fate. Differentiation proceeds via a series of distinct, well-characterised, synchronous and effectively homogeneous progenitor populations, providing an excellent system for studying the molecular control of pluripotency and differentiation. This system is also amenable to manipulation, making it ideal for use in small molecule or genetic screens for agents that affect differentiation and development. Current Projects
Current projects in the lab have evolved out of the Rathjen Laboratory (and are being pursued on a collaborative basis). These include:

1.      Identification of changes in key epigenetic marks as ES cells undergo directed differentiation. The aim is to identify genes and epigenetic signatures that will allow us to lock in cell fate choice, reducing the presence of contaminating cell types arising from alternate cell fates.
2.      Understanding how key pluripotent transcription factors are regulated by signal transduction pathways. This will allow us to improve the growth and manipulation of pluripotent cells (and potentially improve the efficiency of iPS cell formation) using growth factors or chemicals.
3.      Characterisation of the ICM/ES cell transcription factor, CRTR1, in ES cells.

Entry last updated: Tuesday, 26 May 2009