Supervisor View Full Details 2nd

• genetics, genomics and molecular biology
• cell and developmental biology/regenerative medicine
• cancer/oncology

• Medicine
• Surgery
• Pathology

• Dermatology
• Gastroenterology
• Oncology

Work in the functional genomics group (FGG) focusses on the use of cutting-edge genomics technologies (e.g., ChIP-Seq, RNA-seq, CRISPR-Screens) and aligned integrative bioinformatics strategies to investigate transcription factor de-regulation in disease with a particular interest in the p53 family. Through better understanding the genome-wide targets, mechanism of action and consequences of de-regulation of key transcription factors, we aim to identify altered genes or processes which could be exploited for diagnostic or therapeutic application.

My groups work is somewhat disease agnostic, with our project closely with large multidisciplinary translational teams with current funding from BBSRC, MRC, CRUK, PCUK-Movember, Bowel Research UK and Innovate UK. Our current funded work is focussed on Colorectal, Prostate and Squamous cancers as well an interest in homeostasis of Skin and other barrier tissues. We also have a burgeoning interest in the development novel genomics assays, analysis methodologies and easy to use analysis tools.

My group are actively involved in the CRUK ECMC-network with number of active Clinical-Translational studies of relevance to potential projects for the ICAT programme. Our translational work is focused on using functional genomics studies in cutting-edge models to identify targetable vulnerabilities induced by standard-of-care (SoC) treatments in genetically defined subsets of patients.

Research from our group has supported a first-in-man multi-centre Phase-1 trial of global pharma Eli-Lilly’s CDC7 funded by the CRUK funded New Agents Committee, for which I am Co-Investigator and Scientific lead (Chief investigator Richard Wilson University of Glasgow/CRUK Beatson Institute). The trial and associated pre-clinical work in my laboratory, aims to establish the safety of the drug and its potential for targeting a subset of mutant p53 expressing colorectal cancers (identified from work in my group and the colorectal team) and other cancer types with high p53 mutation frequency. This trial is about to enter dose-expansion phase in colorectal and squamous cancer, during which we will be collecting clinical samples for further Biomarker/translational studies. There is therefore an opportunity for clinical fellow to work on data generated from this trial as well as continue aligned translational work focussed on SoC combination partners for later phase trials potentially focussed on colorectal, squamous or ovarian cancers.

There are also opportunities related to our recent work funded through CRUK and PCUK-Movember, has highlighted the potential for epigenetic modifying agents, in particular the class-I HDAC inhibitor Entinostat to augment the effects of SoC chemotherapy in colorectal and prostate cancers (Lees, McIntyre et al. PNAS 2020). We are in process of designing pre- and clinical studies to dissect the complex mechanisms through which Entinostat (alone or combination with other EMAS’s) may increase tumour cell killing of SoC, while priming anti-tumour immunity and increasing immune-cell induced tumour cell death.

Finally, based on our interest in de-regulation of homeostasis in skin, there are additional opportunities to explore novel approaches to exploiting the role of p53 (and its family member p63) in regulating stress response, inflammation, and barrier function in skin and other barrier tissues such as colon