I-Cheng Ho

I-Cheng Ho

Associate Professor of Medicine
I-Cheng Ho

The function of many proteins is regulated by post-translational modifications. One such modification is citrullination, which converts peptidylarginine to peptidylcitrulline. This process is catalyzed by the enzymes peptidylarginine deiminases (PADs), including PAD1-4 and PAD6. The physiological role of PADs in the immune system is still poorly understood. However, aberrant citrullination is very likely pathogenic in several human diseases. For example, rheumatoid arthritis (RA), an autoimmune disease affecting 1-2% of the general population in North America, is characterized by the presence of anti-citrullinated protein antibodies. In addition, several major risk factors of RA are associated with local or systemic hypercitrullination. However, how abnormal citrullination contributes to the development of RA or other human diseases is unclear.

Two lines of research are being conducted in my laboratory.

We have identified a molecular signature of RA, which predates the clinical symptoms. The future directions are to understand the cause of the molecular signature and to explore its clinical applications. The ultimate goal is to develop personalized treatments or even cure of RA. This project is highly translational and requires close collaboration with clinicians.

We are also studying the physiological and pathological roles of citrullination. We have discovered that citrullination can alter the function of several transcription factors that are critical for the function of immune cells, including T cells and neutrophils. In addition, we have found several proteins that are citrullinated in an age-specific manner. The future goals are to establish age-specific and organ-specific citrullinome and to understand how citrullination regulates the function of proteins or cells in the context of human diseases.

Contact Information

Brigham and Women's Hospital
Department of Medicine; Division of Rheumatology, Immunology and Allergy
Building for Transformative Medicine (BTM)
60 Fenwood Road, Room 6002M
Boston, MA 02115
p: 617-525-1005