Factor VIII alloantibodies that disrupt haemostasis (inhibitors) present the biggest challenge to treatment of haemophilia A in the developed world. Despite the CD4 T cell response being pivotal to the alloresponse, cohort studies have only concluded class II HLA association to be a weak determinant of inhibitor risk. However, it may be more informative to analyse individual HLA peptide presentation and develop techniques to better define the specificity of such inhibitory antibodies.
Since joining the Blizard Institute in 2009, Dan secured an Early Career Investigator award from the internationally competitive Bayer Hemophilia Awards Program to develop a high throughput, structural mimic peptide array to define the molecular specificity of alloantibodies against factor VIII ( September 2010). In May 2011, he was awarded a British Society of Haematology Early Career Fellowship to support his evolving interest in T cell epitope prediction using an in silico platform and applied artificial intelligence algorithms to risk stratifying inhibitor formation in haemophilia. This work will form a satellite study to the established international INSIGHT study looking at inhibitor risk in patients with mild and moderate haemophilia A.
Dan has recently joined the UK Haemophilia Centre Doctors’ Organisation national inhibitor working party and is working with the chair, Dr Peter Collins (Arthur Bloom Haemophilia Centre, Cardiff) and other working party members to identify a translational research programme utilising the national cohort. Of particular current interest is the immunological basis of the recent recognition of a bimodal lifetime inhibitor risk, with a previously unrecognised increase risk later in life in addition to the well recognised early factor VIII exposure risk of inhibitor formation.
Dan has additional research collaborations with Prof Brohi’s Trauma research group co-supervising a PhD student and contributing to the established Trauma coagulopathy research group. Work with Lochana Nanayakkara at The Dental Institute aims to identify issues relating to dental work in patients with an inherited bleeding disorder.