The McLauchlan Group
My group is interested in a number of topics on HCV infection and aims to link our findings from investigating infection in vivo with in vitro model systems that reproduce the infectious process in the laboratory. Some of the questions we are trying to address include:
1. What controls the variability of the virus in populations, individuals and at the single cell level and how does the virus evolve?
2. What are the mutations in the virus genome that may give rise to resistance, especially the new DAAs that directly target the virus proteins?
3. Do the different genotypes elicit the same responses in the liver and what mechanisms may drive distinct responses?
4. What are the host factors that regulate infection and how may the virus overcome such defence systems?
5. Does the virus cause premature biological ageing, and does this contribute to liver and other organ disease?
6. What are the biomarkers associated with increased risk of disease progression?
Determining the mechanisms that underlie the outcome of HCV infection relies on in vivo data derived from well-characterised clinical cohorts. This strategy also needs a suite of technologies and analytical tools. Below is a brief outline of two large consortia with which the group is intimately involved.
HCV Research UK
We are one of the founding members of the HCV Research UK consortium, which was established to promote translational studies into HCV infection in the UK. The consortium was funded by the Medical Research Foundation to create a national cohort of 10,000 HCV-infected patients, supported by an infrastructure consisting of linked databases to hold clinical data and patient specimens in a biorepository. The CVR administers HCV Research UK and houses its biorepository. Following successful NIHR portfolio adoption, the recruitment network for HCV Research UK has grown from 18 to 60 sites. Patient recruitment has reached 10,300 and the initiative has attracted 50 applications to access data and samples for wide-ranging research activities, including provision of 'real world' clinical data for regulatory bodies such as the FDA, EMA and NICE. HCV Research UK has also acted as the central data and specimen repository for the NHS Early Access Programme (EAP), which has provided new all-oral, IFN-free therapies to patients with advanced liver disease before NICE approval. More than 700 EAP patients have been recruited into HCV Research UK, making it one of the largest cohorts receiving new therapies for which collated data and serial samples are available.
In addition, we are key partners in the STOP-HCV consortium, which is led by the University of Oxford. This is a MRC-funded study on stratified medicine which aims to optimise treatment options for infected patients. Samples held in the HCV Research UK biorepository at the CVR underpins much of the scientific strategy for STOP-HCV (for viral and host genomics, biomarkers, immunophenotyping). We also collaborate with members of STOP-HCV on the development of pipelines and bioinformatics for viral sequencing.