|Scanned image of a SNP microarray|
|Image of a peripheral blood film at x100 magnification showing multiple mature lymphocytes with condensed nuclear chromatin and basophilic cytoplasm consistent with chronic lymphocytic leukaemia. Some prolymphocytes are also present.|
Dr, University Research Lecturer
TRANSLATIONAL GENETICS: BRINGING RESEARCH INTO CLINICAL PRACTICE
We aim to develop advanced technologies for use in the UK NHS and healthcare services globally and to translate research findings into clinical practice for a range of clinically important conditions.
Our laboratory is affiliated with the Genomic Medicine Theme of the Oxford NIHR Biomedical Research Centre (BRC), an initiative that helps to drive the translation of research from ‘bench to bedside’.
Much of our work has focused on using microarray technology, an approach that has revolutionized our ability to perform high resolution genome-wide testing. Genetic changes identified include losses and gains of chromosomal material (copy number variants and copy number abnormalities) as well as copy neutral ones. Clinically, these changes may be benign, directly pathogenic or represent risk factors for disease. It is particularly important to identify those that contribute to disease not only to improve molecular diagnostic capability and counselling for families, but also to understand mechanisms of disease and biological pathways that, in the future, may lead to targeted therapies for appropriate patient groups.
Previously, our work resulted in the implementation of microarray testing for the molecular diagnosis of idiopathic learning disability (ILD) within the Oxford University Hospitals NHS Trust (OUHT). Now, microarray testing has been adopted nationally for ILD and has transformed clinical practice globally in this field.
Collaboratively, our work has contributed to the identification of novel syndromes, most notably a recurrent 17q21.31 microdeletion syndrome and 15q24 and 15q13.3 microdeletion syndromes.
To realize fully the potential of microarray testing in clinical practice, we are investigating now other clinical disorders, for example brain malformations and B-cell chronic lymphocytic leukaemia (CLL) and maximizing utility for other applications, for example supporting next generation sequencing (NGS) efforts, assessing the genetic integrity of induced pluripotent stem cell lines and for pre-implantation genetic diagnosis.
Our CLL microarray studies have shown already improved capability over cytogenetic approaches used currently in clinical practice to inform upon diagnosis, prognosis and
treatment selection. Now we are making further advances with the implementation of NGS, targeting specific genes of interest.
However, work is still needed to facilitate data analysis within a molecular diagnostic environment and to exploit fully the results to benefit patients. The goal of this continuing work is to enable individually tailored patient treatments, minimize side-effects and mortality and reduce NHS costs.
In the future, our focus will continue to complement the objectives of the Genomic Medicine Theme of the Oxford NIHR BRC.
Identification of Circulating Genomic and Metabolic Biomarkers in Intrahepatic Cholangiocarcinoma
Winter H. et al, (2019), Cancers, 11, 1895 - 1895
Whole genome sequencing identifies putative associations between genomic
polymorphisms and clinical response to the antiepileptic drug levetiracetam
Vavoulis DV. et al, (2019)
Correction: Whole-genome sequencing of chronic lymphocytic leukaemia reveals distinct differences in the mutational landscape between IgHVmut and IgHVunmut subgroups.
Burns A. et al, (2019), Leukemia, 33
The complete costs of genome sequencing: a microcosting study in cancer and rare diseases from a single center in the United Kingdom.
Schwarze K. et al, (2019), Genet Med
Clinical spectrum of STX1B-related epileptic disorders.
Wolking S. et al, (2019), Neurology, 92, e1238 - e1249