Oxford Molecular Diagnostics
Figure 1: Genome-wide clustering reveals changes in mutation profiles. (A-C) Grouping of somatic mutation profiles for all single nucleotide variants (SNVs). Absolute white blood cell (WBC) and lymphocyte (LY) counts are shown at the top of each figure. The bottom panels show genome-wide SNV frequencies plotted against the 5 time points. Mutation profiles for coding genes are shown as black lines.RESEARCH SUMMARY
The Molecular Diagnostics Centre (MDC) has been designated an NHS England Genomic Medicine Centre and partners with Genomics England in the implementation of whole genome sequencing technology to provide NHS diagnostics. A particular focus of the laboratory is to define molecular-based disease classifiers for cancers and haematological malignancies that underpin precision medicine approaches including risk stratification and rational treatment design.
Using samples from National Cancer Research Network (NCRN) clinical trials, my group is also interested in the evaluation of the clinical utility of whole genome sequencing and was first to publish longitudinal studies of whole genome sequencing (WGS) from chronic lymphocytic leukaemia (CLL) patients undergoing treatment. A current focus of the laboratory is to further characterise hyper-mutated non-coding region in the CLL genome and to examine total RNA expression in CLL.
In my role as the clinical lead for CLL and other lymphoproliferative disorders for the Academic Health Science Network, I am a Chief or Principal Investigator on a number of early and late phase clinical trials that are currently undergoing review by the National Institute for Health and Care Excellence (NICE), which are likely to change clinical practice for treatment of relapsed CLL patients worldwide. I also have a particular clinical focus on Richter’s Syndrome (high grade transformation of CLL) and am the Chief Investigator on the first ever Phase 2 clinical trials for this rare patient group.
RESEARCH THEME
GROUP INFORMATION
RESEARCH SCIENTISTS
Dr Dimitris Vavoulis, PhD, Head of Bioinformatics
Dr Kate Ridout, PhD, senior bioinformatician
Kieran Howard, Clinical Scientist and bioinformatician
Dr Grigore-Aristide Gafencu , MD, PhD and bioinformatician
Dr Anthony Cutts, PhD, Scientific Lead
Helene Dreau, Lead Clinical Scientist
Dr Adam Burns, Lead Scientist Global Health
DPHIL STUDENTS
Ismail Draguma
Niamh Appleby, MD
Sandra Maseno, MD
OPERATIONS
Dr Claire El Moulden, Programme Manager AI-REAL
Gagandeep Batth, Operational manager
Mickey Leonte, Laboratory Logistics Manager
LABORATORY ASSISTANTS
Georgeta Ciuban
Melinda Kormany
Kayleigh Mainwood
Thomas Wenban-Smith
IMPACT
We made significant contributions to Genomics England’s 100,000 Genome Project by producing and analysing the largest whole genome sequencing dataset in CLL. We identified new biological and clinical risk groups that can be used to refine outcome prediction and to identify people with pre-malignancy at risk of progression to malignancy opening the way to early interception studies. We also expect that the NHS will apply these types of analyses to all patients with CLL recruited into clinical trials.
We have developed and validated a liquid biopsy test for earlier and more precise diagnosis of children with EBV-positive Burkitt’s lymphoma in Sub-Saharan Africa that is expected to aid clinicians in the choice of treatment ultimately saving lives of 100s of children every year. We are working with government representatives in Uganda and Tanzania to implement this test.
We hold intellectual property to analyse circulating foetal DNA from maternal plasma for the diagnosis of autosomal recessive diseases starting with haemoglobinopathies and to interrogate circulating tumour DNA for earlier cancer diagnosis. We have created a social enterprise called SEREN to make these technologies available to low-to-middle income countries starting with East Africa.