Rebecca Powell Doherty
Dissecting the biological basis of HLA variation to susceptibility, disease progression, and response to therapies in Crohn’s Disease and Ulcerative Colitis
My work focuses on the development and progression of disease in individuals who have moderate to severe Crohn's Disease or Ulcerative Colitis. I investigate those with a known very strong but so far unexplained genetic predisposition to either severe colitis, or to developing antibodies which neutralise drugs known as anti-TNF biologics used in the treatment of inflammatory bowel disease in order to study the immunological mechanisms that underlie this genetic predisposition.
The genes involved are referred to as the HLA system, which are involved in regulating the immune response - these genes encode proteins that interact with antigens or fragments of antigens. In one aspect of this work, we hope to be able to identify the specific antigens in the environment that trigger severe colitis, informing pathogenesis of disease. In another aspect, we hope to identify the parts of the drugs which are responsible for causing patients to developing neutralising antibodies to biologics. This may allow a rational drug design of a non-immunogenic molecule.