The North West Embryonic Stem Cell Centre

Professor Sue Kimber

BA, MA, PhD

Research Interests

1) Human embryonic stem cells and embryos.

We are characterizing the fate of inner cell matrix (ICM) cells, in terms of survival versus death and maintenance of pluripotency versus cell lineage commitment. We are identifying new pluripotency associated genes in human embryonic stem cells (hESc) and working out their function. We are working on the signling mechanisms by which hESc are maintained with a pluripotent phenotype and investigating their induction along pathways to early specified and committed cell types.  We are particularly interested in the role of the extracellular matrix and matrix associated transducers of signalling like focal adhesion kinase and PI3k and the interaction between growth factor signaling and that from the extracellular matrix.  

We have programmes studying targeted differentiation particularly to mesodermal lineages, and most successfully to cartilage (with Hardingham). We can derive chondrocytes form hESc and induced pluripotent stem cells (reprogrammed form adult fibroblasts) and these cells are able to repair osteochondral defects in immunocompromised mice.  This technology is bieng used to produce new disease models for cartilage related diseases.

We are deriving new hES cell lines from human oocytes and embryos (collaborator Brison) . So far we have derived 9 research grade hES cell lines RCM1 and Man1-8 As part of the North West Embryonic Stem Cell Centre , directors Kimber and Brison:  our goals are to derive hES cell lines under clean room conditions, suitable for use in clinical therapy.

 

Regulation of cell pluripotency in mammalian embryos and ES cells

We are mapping expression of pluripotency genes in murine embryos and using RNAi to knockdown gene function. We have identified important signaling pathways regulating early cell fate decisions and stem cell proliferation using hES cell and a major goal is understanding their roles.

 

The stem cell niche

We aim to elucidate the molecules and mechanisms whereby adhesion to both natural and synthetic substrates control hES status and function . We are also now investigating the siganling from ECM components and how this influences hESc pluripotency survival and fate (In colaboration with Matin Humphries and Andrew Gilmore Wellcome Matric Centre).

 

Gene expression patterns during human embryo development

Representative amplification of mRNAs from single cells and embryos allows us to map gene expression patterns during development of individual human embryos and in single blastomeres. We use microarray analysis for transcriptional profiling of early human development (with Brison). Research aims include understanding the basis of cell pluripotency and fate.

 

Metabolic fingerprinting of human embryos and ES cells

We are analysing culture mediums in which human embryos and ES cells are grown using HPLC, infrared spectroscopy and mass spectroscopy to provide a metabolic "fingerprint" associated with embryo viability and ES cell pluripotency/commitment (collaborators Brison and Goodacre).

2) Implantation

In the cascade of interactions involved during implantation, we discovered a novel steroid regulated mechanism for initial attachment of embryos depending on binding of blastocyst receptors to carbohydrates on uterine luminal epithelial glycoproteins.

Identification of molecules in the human uterus, with similar functions, has begun (with Aplin). Our research involves the role of cytokines particularly Leukemia Inhibitory Factor (LIF) in controlling differentiation of the uterus to allow embryo implantation. We are investigating mechanisms by which LIF controls implantation using LIF-nul