Trinity College Dublin

Skip to main content.

Top Level TCD Links

Cancer Stem Cell Research

Tumorigenesis diagram

In recent years the cancer stem cell (CSC) theory of tumorigenesis has received vastly increased attention. Our department is home to the only pure Cancer Stemness research group in Ireland. It is now generally accepted that most, if not all, cancers are driven by a population of stem-cell like cancer cells. These CSCs can self-renew and differentiate to generate tumors in vivo, thrive in the hypoxic environment of tumors and are resistant to current therapeutics. Thus CSC-targeting is an area through which the efficiency of cancer treatment may be improved.

The primary characteristic defining CSCs is their differentiation capacity. Our group investigates the relationship between the differentiation potential of CSC populations and tumour grade, metastasis, recurrence and chemoresistance. We employ an embryonal carcinoma model of cancer stemness, which we have shown is highly relevant to ovarian cancer (Gallagher et al 2009: d’Adhemar et al 2010: Figures 1 and 2). The group’s primary aim is development of a therapeutically relevant method or targeting CSCs without harming non-CSCs within the body.

Group Leader

Michael Gallagher (B.Sc, PhD) trained in the Stem Cell department at the Genome Institute of Singapore and is primarily interested in transcriptional and post-transcriptional networks that regulate early CSC differentiation. To date we have characterised gene and miRNA expression and modeled translation at a whole genome level, generating substantial lists of putative gene and miRNA targets. This data is used as a platform for functional analysis of the effects of gene and miRNA targeting on CSC differentiation, tumor generation and chemoresistance.

Postgraduate Students and Projects

Salah Elbaruni (B.Sc, M.Sc):

Functional analysis of TGF-beta pathway genes on differentiation on ovarian cancer stem cells. TGF-beta signaling was identified by array analysis of CSCs and Salah has characterised this pathway in CSCs and is currently functionally analyzing the role of TGF-beta signaling in CSC differentiation.

Yvonne Salley (B.Sc, M.Sc):

Generation of stem cell-like cells from prostate cancer. Yvonne’s work is part of the Cancer Research Ireland (CRI) funded Prostate Cancer Research Consortium and involves generation and characterization of stem cell-like holoclones from prostate cancer cells.

Sebastian Vencken (B.Sc):

Functional analysis of miRNAs involved in differentiation of ovarian cancer stem cells. This CRI funded project assesses the necessity of miRNAs identified in our data set of the differentiation of CSCs.

Aoife Cooke (B.Sc):

The role of TLR/MyD88 signaling in ovarian cancer stem cell differentiation and chemoresistance in normal, hypoxic conditions. This CRI funded project exploits our identification of a TLR/MyD88 switch in CSC differentiation. Aoife is fully characterizing the role of TLR4/MyD88 signalling in CSC differentiation and chemoresistance in normal and hypoxic conditions.

Brendan Ffrench (B.Sc):

Isolation and characterization of novel cancer stem cell populations from ovarian cancer. This project if funded by The Emer Casey Foundation and will establish a protocol for the isolation of multiple CSC populations from chemoresistant and chemosensitive primary and recurrent ovarian cancers.

Charles d’Adhemar (M.D):

TLR4/MyD88 expression in ovarian cancer samples. Charles has completed a comprehensive analysis of TLR4/MyD88 expression in ovarian tumour samples, associating them with tumor grade (d’Adhemar et al 2010).

Aoife Canney (M.D):

Assessment of EMT in ovarian cancer. Tumor cells are believed to travel to secondary sites and establish secondary malignancies via a process termed epithelial-mesenchymal transition (EMT). Aoife is characterizing this process in ovarian CSCs.

For more information please contact Michael Gallagher: gallagmi@tcd.ie

References

Gallagher MF, ElBaruni S et al 2009: Regulation of microRNA biosynthesis and expression in 2102Ep embryonal carcinoma stem cells is mirrored in ovarian serous adenocarcinoma patients. Journal of ovarian research, 2: 19.

Heffron CCBB, Gallagher MF et al 2007: Global mRNA analysis to determine a transcriptome profile of cancer stemness in a mouse model. Anticancer research, 27:1319-1324.

D’Adhemar C, Gallagher MF et al 2010: Functional Expression Analysis of TLR-4 and MyD88 in Epithelial Ovarian Neoplasia. In prep

Figure 2

Back to Research Project Index


Last updated 21 September 2016 Paul Smyth (Email).