Scripps Research Logo

The Mowen Laboratory

Research

Posttranslational modifications of proteins allow cells of the immune system to initiate a rapid but appropriate immune response to pathogens. Our lab studies how two different modifications of the arginine amino acid – methylation and citrullination – contribute to the immune response.

PRMTs

Protein Arginine Methyltransferases (PRMTs) catalyze the addition of a methyl group from S-adenosylmethionine (SAM) to guanidino nitrogen atoms on arginine residues. Many biological processes are regulated by PRMTs, including transcription, DNA repair, RNA processing, and signal transduction. PRMT1 is the predominant arginine methyltransferase, accounting for > 85% of cellular PRMT activity. Aberrant PRMT1 activity has been associated with cardiovascular, malignant, infectious, and autoimmune disease, making it a viable therapeutic target for several indications.

We have previously demonstrated a key role for arginine methylation in regulating T helper cell cytokine expression. Arginine methylation of NIP45 (NFAT-interacting protein, 45kD) by PRMT1 augmented its interaction with NFAT and resulted in elevated cytokine production in T helper cells. However, it is unlikely that NIP45 is the only substrate of PRMT1 in T helper cells or that PRMT1 is the only PRMT that regulates cytokine production in T helper cells. Our long-term goal is to determine the role of PRMT1 in regulating T helper cell function.

PADs

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disease affecting ~ 2% of the world population. Plasma and synovial biopsy specimen from patients with rheumatoid arthritis (RA) contain high levels of citrullinated proteins, and anti-citrullinated peptide antibodies (ACPA) exhibit high specificity and sensitivity as diagnostic markers of the disease.  Proteins containing citrulline are generated through posttranslational modification of arginine residues in a reaction catalyzed by the Ca2+-dependent peptidyl arginine deiminases (PAD). PAD2 and PAD4 expression is closely linked with inflammation in RA synovial tissue. Though citrullination is associated with inflammatory conditions, the process by which PADs are activated during the disease process is unknown. Our long-term goal is to understand the contribution of PAD2 and PAD4 to RA disease pathogenesis.

Our laboratory enjoys a strong collaboration with Dr. M.G. Finn’s laboratory in the Department of Chemistry to generate novel tools to study PAD and PRMT function. Additionally, the TSRI community is rich in immunology expertise, and our affiliation with the Department of Chemical Physiology, in particular, gives us special access to innovative technology platforms in the areas of genomics, proteomics, and metabolomics. Our research has identified a unique contribution of the PRMT and PAD family members in T cell  and mast cell function, providing new therapeutic targets, particularly for autoimmunity.

___________

Lab Home
___________

Research
___________

People
___________

Positions
___________

Publications
___________

Lab Photos
___________

Inspired by Immunology
___________

Links
___________

Contact Us
___________