Faculty

Kerri Mowen 
Assistant Professor
CHEMICAL PHYSIOLOGY
TSRI - 2005

Education 
Ph. D., University of California, San Diego, 2000

Research Focus 
Regulation of T helper cell function by Arginine Methylation


When naive T helper cells first encounter antigen, they are induced to differentiate into one of two lineages. Th1 cells produce the cytokine interferon gamma (IFNg) and are important for defending against infection with intracellular microbes. Th2 cells produce the cytokine interleukin 4 (IL-4) and are necessary for combating extracellular pathogen infections like parasitic worms. The balance between Th1/Th2 subsets determines the susceptibility to malignant, infectious, allergic, and autoimmune diseases. The improper development of Th2 cells can lead to allergy and asthma, while an overactive Th1 response can lead to autoimmune diseases like diabetes. Therefore, manipulation of Th1/Th2 subsets provides an intriguing avenue of therapy.


Posttranslational modifications of proteins within T cell receptor signaling cascades allow T lymphocytes to initiate a rapid but appropriate immune response. We have demonstrated a key role for methylation of arginine residues in regulating T helper cell cytokine production, including IFNg and IL-4. In my laboratory, we are investigating a broader role for arginine methylation in regulating T helper cell and mast cell function by identifying new substrates using expression library screening and mass spectrometry, determining the mechanism by which arginine methylation regulates these substrates, and establishing the role for the arginine methylation enzymes in the immune response by creating mice with targeted deletions of these enzymes. Understanding the molecular events which control T helper cell function would provide useful tools to modulate the Th1/Th2 response.

Selected References 
Mowen K., Tang J., Zhu W., Schurter B T, Shuai K, Herschman H., and David M. (2001) Arginine Methylation of STAT1 modulates IFNa/b induced Transcription. Cell. 104:731-741.

Mowen KA, and David, M. (2001). Cytokine activation of transcription. Genet Engineering, Principles and Methods. Ed. J. K. Setlow, Kluwer Academic/Plenum Press

Mowen K.A., Schurter B.T., Fathman J., David M, and Glimcher L. H. (2004) Arginine Methylation of NIP45 Modulates Cytokine Gene Expression in Effector T Lymphocytes. Molecular Cell. 15:559-571.

Mowen K. A. and Glimcher L.H. (2004) Signaling Pathways in Th2 Development Immunological Reviews 202: 203-222.