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Full NameDr Aideen Ryan

Department:Pharmacology & Therapeutics

Organisation:National University of Ireland Galway

Webpage:nuigalway.ie

Email Address:Email hidden; Javascript is required.

Research Fields

  • infectious disease and the immune system
  • cell and developmental biology/regenerative medicine
  • cancer/oncology

Postgrad Medical Specialties

  • Medicine

Medical Subspecialties

  • Gastroenterology
  • Haematology
  • Immunology
  • Pharmacology

My Work

Dr Aideen Ryan’s research group is focussed on identifying therapeutically targetable stromal cell mediated mechanisms of immune suppression in the tumour microenvironment with a view to enhancing anti-tumour immune responses, and improve therapeutic outcomes in cancer. As part of the larger immunology group at the Regenerative Medicine Institute, Dr Ryan’s research group has significant experience in tumour immunology, stromal cell immunology and evaluation of immune responses in pre-clinical tumour and allogeneic transplantation models. Current research is funded by Science Foundation Ireland, Irish Cancer Society and Industry-funded collaborations (Janssen and AbbVie).

Some of our key discoveries in the past include: Identification of the role of Fas ligand in immune suppression in a pre-clinical model of colon cancer; Identification of the effect of stromal cell differentiation on immune-regulatory ligand expression and host immune responses in vivo, and characterization of the role of NF-κB in the molecular regulation of colon cancer metastasis and host anti-tumour immunity in vivo.

www.linkedin.com/in/a-e-ryan
www.remedi.ie

Potential Projects

Background :
Tumors have been described as wounds that do not heal, as they are usually infiltrated with multiple types of immune cells, which together with supporting stromal cells comprise the tumor microenvironment [1]. Data from our laboratory and others [2] indicates that mesenchymal stromal cells (MSCs) are precursors of cancer associated fibroblasts, cells that are identified in tumours by their expression of α-SMA. Stromal cells maintain the structural integrity of tumours and impact tumour progression through multiple mechanisms, including the secretion of cytokines, and immunomodulatory mechanisms. In a model of colon cancer metastasis, we have previously shown that that cancer cell inflammation can regulate tumor associated macrophage polarization (3). This PhD proposal aims to build on this exciting data and to comprehensively determine the functional consequences of how colon cancer cell associated inflammation can affect the immunoregulatory functions of stromal cells.

Proposed Project:
This proposed PhD project involves a detailed analysis of the mechanisms of action of stromal cell in the colon cancer tumour microenvironment. In this project, the PhD student will work alongside the post-doctoral researchers and clinical collaborators (Prof LJ Egan, NUIG/UCHG) to isolate and characterize stromal cells from colon cancer/ inflammation associated colon cancer clinical biopsies. These stromal cells will be extensively characterized using flow cytometry and immunological co-culture assays. The outcome of this research project will be identification and characterization of novel immunoregulatory transcriptional and signaling pathways in stromal cells that enhance their immunoregulatory functions. The PhD student will also investigate if these pathways are regulated by the presence or absence of colon cancer associated inflammation. The outcome of this research project should contribute significantly to our understanding of the extent to which inflammation can impair different aspects of the anti-tumor immune response.

References
(1) Turley S et al., Immunological hallmarks of stromal cells in the tumour microenvironment Nature Reviews Immunology 15, 669–682 (2015) doi:10.1038/nri3902
(2) O’Malley G, Ryan AE et al., Mesenchymal stromal cells (MSCs) and colorectal cancer - a troublesome twosome for the anti-tumour immune response? Oncotarget, (IF 6.3) PMID 27542276
(3) Ryan AE et al., Targeting colon cancer cell NF-κB promotes an anti-tumour M1-like phenotype and inhibits peritoneal metastasis. Oncogene, Mar 19;34(12):1563-74 (IF 8.6) PMID 24704833