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Blizard Institute - Faculty of Medicine and Dentistry

Dan Hart, BSc, MBChB, MRCP, FRCPath, PhD

Senior Clinical Lecturer in Haematology & Honorary Consultant in Haematology

Centre: Immunobiology

Email: d.hart@qmul.ac.uk
Telephone: 07734 696479

Profile

 

Dan completed his undergraduate medical training at Bristol University in 1995, including a BSc in Cellular and Molecular Pathology. He then completed his general medical training and in Bristol, Gloucester and Southport, Australia. He gained his MRCP in 1998.

On returning to the UK in 2000, he joined the Bristol Childrens’ Hospital Bone Marrow Transplant team as a clinical fellow under Prof Tony Oakhill where his interest in immunological complications of disease and allogenicity started.
Moving to the Haematology training rotation of University College London Hospital in 2001 enabled him to further his transplantation experience under Professors Stephen Mackinnon / David Linch and then pursued his PhD at UCL supervised by Professor Hans Stauss and Dr Emma Morris. His thesis focused on antigen specific T cell responses and gene therapy techniques to redirect the antigen specificity of naïve T cells.

His clinical interest in haemostasis and thrombosis with Prof Machin, Dr Marie Scully and Dr Hannah Cohen, led to a Senior clinical fellowship under the directorship of Prof Ted Tuddenham at the Royal Free Haemophilia & Thrombosis Centre after completion of his FRCPath in January 2009. He was then appointed as Senior Lecturer in Haematology at Barts and The London School of Medicine & Dentistry, Queen Mary University London, in Sep 2009 to join the clinical team in the Haemophilia centre and thrombosis service, whilst setting up a research programme in immunohomeostasis in the Blizard institute.

 

Summary

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.

Teaching

Dan contributes to undergraduate lectures and Problem Based Learning. He also organises the first year Fundamentals of Medicine physiology block. He is a clinical supervisor for London Deanery Haematology trainees at The Royal London Hospital. He lectures on local and national training days for haematology registrars and clinical nurse specialists.

Topics for PhD supervision:

Immunological basis of allo or autoantibody formation


Research

Research Interests:

  • Identification of B and T cell epitopes derived from therapeutic factor VIII or IX to enhance understanding of neutralising antibody formation.
  • Application of artificial intelligence neural networks to apply high throughput in silico prediction.
  • Development of antigenic peptide prediction pipeline as a translational tool to underpin future trials and national protocol development.

Publications

  


View all Dan Hart's Research Publications at: http://www.researchpublications.qmul.ac.uk

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