MRC Human Genetics Unit
Medical Research Council Human Genetics Unit

Maria Christophorou: Protein Regulation in Health and Disease

Research Programme

M.Christophorou research

 

The PTM citrullination (or deimination) is the conversion of an arginine residue to the non-coded amino acid citrulline. It is carried out by enzymes called peptidylarginine deiminases (PADIs) and can modulate a protein's function by altering its structure, changing its sub-cellular localisation and affecting its interactions with other molecules. Our recent work has shown that citrullination regulates pluripotency, the ability to generate any type of cell from a stem cell, which holds great promise for regenerative medicine. Notably, abnormal citrullination is a pathological feature of diseases such as autoimmunity (rheumatoid arthritis, multiple sclerosis, ulcerative colitis, psoriasis), neurodegeneration (Alzheimer's and prion diseases), atherosclerosis and cancer. In certain cases it serves as a marker of diagnostic and prognostic value, while its inhibition has shown early promise in disease-based experimental systems. Despite the likely mechanistic importance of citrullination in both cell physiology and disease, it remains largely unexplored.

The central aims of our work are to define how PADIs are regulated and understand how their deregulation contributes to disease development. We employ a combination of biochemical, molecular and cell biological approaches, as well as in vivo model systems. We hope that this work will significantly advance our current understanding of citrullination and explore new regulatory mechanisms involved in both physiology and disease.