WHERE WERE YOU BEFORE RECEIVING THIS AWARD?
Traditionally, communication between cancer cells and surrounding stromal cells was believed to be governed primarily by direct cell-tocell contact as well as secretion and uptake of soluble factors. In recent years information exchange via secreted extracellular vesicles (EVs) has gained much attention and cancer-derived EVs are regarded as having promising potential as therapeutics and disease biomarkers. However, experimental challenges to separate EVs from non-EV material in biofluids existed that had to be overcome in order to understand and exploit EVs in translational cancer medicine.
YOUR RESEARCH PROJECT IN LAY TERMS
Extracellular vesicles (EVs) are small spherical vesicles that are released from all cells in the body and can be taken up by a variety of other cell types. Released EVs contain components of their cell of origin, thus they act as a surrogate marker of the cell from which they were released. When taken up by other cells, EVs pass information to recipient cells and can alter recipient cell function. EVs are released in higher numbers from cancer cells compared to normal cells and thus are highly abundant in body fluids including blood, bone marrow, saliva and urine, making them an easily accessible means of diagnosing and monitoring cancer in real time. This approach has many advantages over invasive tumour biopsies that is currently used for diagnosing and monitoring cancer.
This project focussed on developing methods to separate EVs from the highly abundant non-EV components present in human blood. Purified EVs are characterised to identify components that differ from normal EVs and that correlate with disease stage and prognosis. A better understanding of these factors may lead to development of a non-invasive blood test for cancer diagnosis and monitoring.
HOW HAS ISSF HELPED YOUR RESEARCH CAREER?
This award enabled me to study the function of extracellular vesicles during cancer progression, metastasis, and drug resistance using clinical patient specimens. We have overcome experimental challenges for EV separation and developed new approaches for their characterisation. This work has contributed to new interdisciplinary collaborations comprising researchers, clinicians and industry partners to exploit EVs as non-invasive liquid biopsies with potential to inform clinical decisions and ultimately contribute to the implementation of personalised medicine.
TANGIBLE OUTPUTS AS A RESULT OF RECEIVING THE AWARD
Funding >€2.5 million awarded since 2017:
- 2019 Irish Cancer Society Biomedical Scholarship €130K
- 2019 Collaboration with Vejle Hospital, Denmark €180K
- 2019 UCD Equipment Scheme €320K
- 2020 Science Foundation Ireland €330K
- 2021 UCD Equipment Scheme €150K
- 2021 IRC Scholarship €110K
- 2022 Science Foundation Ireland Infrastructure Award €915K
- 2022 Horizon Europe €400K
Publications
- A comparison of methods for the isolation and separation of extracellular vesicles from protein and lipid particles in human serum. Brennan K, Martin K, FitzGerald SP, O'Sullivan J, Wu Y, Blanco A, Richardson C, Mc Gee MM. Sci Rep. 2020 Jan 23;10(1):1039. doi: 10.1038/s41598-020-57497-7. PMID: 31974468 In this highly cited manuscript Brennan et al conducted a comprehensive comparison of all currently available methods for the isolation and separation of EVs from non-EV protein and lipid particles in human serum. The study makes a valuable contribution to the field of EV biomarker discovery and validation
- Cyclophilin A regulates secretion of tumour-derived extracellular vesicles.Wu Y, Brennan K, Fernández AB, Mc Gee MM.Transl Oncol. 2021 Aug;14(8):101112. doi: 10.1016/j. tranon.2021.101112. PMID: 33984826
Conference Presentations
- International Society of Extracellular Vesicles annual conference, Barcelona, Spain. May 2-6 2018. Poster Title: An optimised workflow for the isolation and purification of extracellular vesicles from small serum volumes
- International Society of Extracellular Vesicles annual conference, Kyoto, Japan. April 24-28, 2019. Poster Title: Investigation of a novel role for Cyclophilin A during extracellular vesicle signaling in cancer
- MRS-ISEV The first joint conference on Extracellular Vesicles in Cancer, Nashville Tennessee USA. August 2-4th 2019 – Poster Title: Characterisation and next-generation sequencing-based miRNA expression analysis of chronic lymphocytic leukaemia extracellular vesicles (EVs)
Outreach
Members of my lab are actively involved in outreach activity. Outreach Awards:
- 2022 Professor Patrick Johnston IACR Award for Excellence in Cancer Research Outreach (Rebecca Sheridan)
- 2022 UCD Engage Winner (Rebecca Sheridan)
- 2019 UCD Engage Winner (Rebecca Gorry)
- 2015 UCD Engage Winner (Paul Lavin)
WHAT DID THE AWARD MEAN TO YOU PERSONALLY?
The Award allowed me to develop new research expertise within my group that has seeded several new national and international interdisciplinary collaborations and opened up new exciting research possibilities.