Inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease are chronic
relapsing disorders of the intestinal tract for which their is still no cure. Current treatment options
aim to suppress inflammation however there are a large number of patients that do not respond
or have a loss of response to treatment. Hence, there is a great need for new non-toxic therapies.
One appealling alternative approach is the inhibition of the oxygen sensing enzymes prolyl
hydroxylase 1, 2 and 3 which has been proven to be protective in experimental models for IBD.
However, due to the risk of unwanted side-effects their use in the clinic is hampered. Isoformspecific
targeting could represent a way to overcome these issues. In this regard, we showed that
the lack of prolyl hydroxylase 1 specifically in immune cells ameliorates the course of experimental
UC. However, some important questions still remain which we will address in the following
1) Evaluate the therapeutic potential of specific Phd1 targeting in chronic models of colitis and
2) Assess the impact of Phd1 targeting on inflammation-linked intestinal complications (i.e. fibrosis
and colitis-associated cancer).
3) Dissect the mechanism(s) by which PHD1 targeting elicits anti-inflammatory properties by
analysing its effect in innate and and adaptive immune cells of healthy individuals and IBD