TGU Talk: “A Crohn’s & Still’s risk gene revamps core purine metabolism”

We investigate the biology of Crohn’s disease and ulcerative colitis. These are two inflammatory bowel diseases that can affect individuals at any age, most often in early adulthood. They emerge from a complex gene – environment interaction. The actual triggers remain still unknown.

Employing and developing a wide range of technologies, from complex genetic models to sophisticated liquid chromatography mass spectrometry, we explore the major biological mechanisms that are affected by risk genes of inflammatory bowel disease. This has generated important insights into how autophagy and endoplasmic reticulum stress collude to drive a pathological unfolded protein response. And most recently led to the discovery of a very fundamental purine enzyme that enables a metabolic cycle balancing electron transfer into mitochondria and controlling immunometabolism of macrophages.

Our laboratory is based in the Cambridge Institute of Therapeutic Immunology and Infectious Disease.

We also run a clinical trials unit, based at Addenbrooke’s Hospital and the Clinical Research Facility, which translates novel insights into therapeutic opportunities for our patients with inflammatory bowel disease. This ranges from proof-of-concept studies and early phase clinical development programmes of novel mechanisms of action up to late phase pivotal registration trials.

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