Examining role of epigenetic alterations as biomarkers in gastrointestinal diseases
Inflammatory Bowel Disease – Ulcerative Colitis
Preliminary data from our group as well as literature demonstrate a significant involvement of DNA methylation alterations in the pathogenesis of Ulcerative colitis. Our Science Foundation Ireland-funded programme – DETECT as well as research programme funded by the European Crohn’s & Colitis Organisation – DYNAMIC, aims to identify DNA methylation signatures that enable the prediction of treatment response, disease progression as well as development of secondary manifestations associated with Ulcerative colitis across both adult and paediatric patient populations.
Metastatic colorectal cancer
Work from our group has enabled us to identify a tumour-specific novel DNA methylation signature derived from metastatic colorectal cancer encompassing gene promoter and enhancer regions. Through an Irish Research Council-funded research project, we are further interrogating the therapeutic potential by applying large CRISPRi screens to colorectal cancer cell lines. In parallel, we aim to further validate the role of this signature in predicting survival and treatment response in metastatic colorectal cancer patients.
Examining role of epigenetic alterations as novel therapeutic targets in gastrointestinal diseases
Inflammatory Bowel Disease – Ulcerative Colitis
We have developed novel in vitro and cell line-based 3D printed models that recapitulate the inflammatory microenvironment associated with IBD. Using these model systems, we are currently evaluating the anti-inflammatory potential of current FDA approved as well as novel epigenetic targeting agents. The proof-of-concept data generated from these studies will ultimately enable us to further evaluate these potential therapeutic options using in vivo models.
Colorectal cancer
Through ongoing collaboration with the Department of Medicinal Chemistry, Royal College of Surgeons in Ireland, we are evaluating novel derivatives of clinically approved histone deacetylase inhibitors (HDACi) that have been developed to prevent premature metabolic degradation in solid tumours such as colorectal cancer. To this end, using both 2D and 3D model systems we are carrying out extensive phenotypic and multi-omic analysis to elucidate the molecular impact of these novel HDACi derivatives.
Applying machine learning approaches to identify novel molecular mechanisms and therapeutic targets in gastrointestinal diseases
Inflammatory Bowel Disease – Ulcerative Colitis & Crohn’s Disease
The project supported through the Science Foundation Ireland-funded Center for Research Training in genomics data sciences aims to develop and apply a machine learning-based analysis pipeline to identify novel features and therapeutic targets using large multi-omic data sets derived from both adult and paediatric Ulcerative colitis and Crohn’s disease patients.
EpiGastroDRG 