Maureen J. O’Sullivan


Maureen J. O’Sullivan

Consultant Paediatric Pathologist, Professor

Professor O’Sullivan is a consultant paediatric pathologist working at CHI at Crumlin (formerly OLCHC), which houses the national paediatric oncology-haematology unit. Her specific interest is in paediatric solid tumours and, in the research setting, the genetics, epigenetics and biology of these tumours. Professor O’Sullivan’s group particularly focuses on sarcomas and paediatric renal tumours. They have characterised several novel chromosomal translocations and studied the biological impact these have on cell biology. The work has benefits in terms of diagnosis, prognosis, biological understanding and novel therapeutic development for these rare cancers, which are all too often neglected despite their aggressive behaviour.

Maureen J. O’Sullivan

Consultant Paediatric Pathologist, Professor

The role of transcription factors in sarcomagenesis

Professor O’Sullivan’s group identified and characterised in 2012 the then only known genetic mutation recurrently seen in Clear Cell Sarcoma of Kidney (CCSK), and have been working on the biologic implications of that mutation (YWHAE-NUTM2 fusion) since then, with very exciting results. Recently, one further mutation was identified in CCSK – this is within the BCOR gene which has a role in epigenetic regulation of gene transcription. Professor O’Sullivan’s group have now studied a very large cohort of cases of CCSK collected from international sources to total 159 tumours for these two genetic mutations. Their findings show distinct subsets of CCSK with the BCOR and YWHAE alterations. They have adopted several technical approaches specifically to investigate the epigenetic effect of BCOR ITD in cells. Their studies on YWHAE-NUTM2 are already advanced and they will be uniquely positioned to draw comparisons between the molecular mechanisms in their contributions to CCSK oncogenesis.

An Exploration of Novel Therapeutic Targets in Malignant Rhabdoid Tumour

Malignant rhabdoid tumour (MRT), one of the most aggressive human cancers, afflicts very young children and has extremely poor outcomes. Despite its highly malignant nature, MRT bears mutations in just one gene known as SMARCB1. This gene encodes a protein that is important in the organization of the DNA (the genetic blueprint) within the cell thereby having a major influence on which genes are actively expressed within that cell. We have a number of aims, including working out what cell type rhabdoid tumour arises from, as this is not known and can be important in choosing best treatment. The DNA within a cell is arranged into a structure called chromatin and the precise arrangement is quite dynamic and highly regulated. SMARCB1 is a subunit of a multiprotein complex involved in this regulation of chromatin’s organisation. Therefore, we aimed to work out what exactly happens in terms of DNA organisation when SMARCB1 is inactivated (as occurs in the MRT tumour cell setting) and how this contributes to the cancer developing, but then also to establish what happens when we put SMARCB1 back into the tumour cells that are missing it. Revealing the changes in the chromatin that follow on from loss of, and reintroduction of, SMARCB1 would allow for the identification of vulnerabilities in the MRT cancer cell that could be targeted in new treatments for MRT.

The list of publications below is automatically derived from MEDLINE/PubMed. As a result, there may be incorrect or missing publications.

Chowdhury T, Prichard-Jones K, Sebire NJ, Bier N, Cherian A, Sullivan MO, O'Meara A, Anderson J, 2013 Jan, Persistent complete response after single-agent sunitinib treatment in a case of TFE translocation positive relapsed metastatic pediatric renal cell carcinoma. J Pediatr Hematol Oncol, DOI: 10.1097/MPH.0b013e318266bf34

Funding Agency:Health Research Board – Clinician Scientist Award
Project Title:The role of transcription factors in sarcomagenesis with an emphasis on clear cell sarcoma of kidney and undifferentiated sarcoma
Start Date/End Date:December 2012 – May 31st, 2018
Funding Agency:The National Children’s Research Centre
Project Title:Characterization of novel chromosomal translocations in sarcomas with emphasis on t (17;19) and t (10; 17) as initial investigations.
Start Date/End Date:August 2008 – January 2011
Funding Agency:The National Children’s Research Centre
Project Title:An exploration of biological targets for novel therapeutics in rhabdoid tumours
Funding Agency:The National Children’s Research Centre
Project Title:Pathogenesis of Clear Cell Sarcoma of Kidney-establishing the relative roles of BCOR and 14-3-3e-NUTM2
Start Date/End Date: 03/04/2017- ongoing
Name:Professor Ivo Leuschner
DepartmentPathology, Division of Paediatric Pathology
Institution:Christian-Albrechts University Kiel,
Country:Germany
Name:Dr. Christian Vokuhl
DepartmentPathology
Institution:Christian-Albrechts University, Kiel
Country:Germany
Name:Professor Manfred Gessler
DepartmentTheodor-Boveri-Institute/Biocenter
Institution:Developmental Biochemistry, and Comprehensive Cancer Center Mainfranken, Wuerzburg University, 97074 Wuerzburg
Country:Germany
Name:Professor Norbert Graf
DepartmentPaediatric Oncology and Hematology,
Institution:Saarland University Hospital, Homburg
Country:Germany
Name:Professor Adrian Bracken
DepartmentGenetics
Institution:Smurfit Institute, Trinity College, Dublin
Country:Ireland
Name:Dr. Gerard Cagney
DepartmentConway Institute
Institution:University College Dublin
Country:Ireland