Scripps Research Joint Appointments

Faculty, Kellogg School of Science and Technology

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.

Education

B.A., Biological Sciences, Southern Illinois University, 1996
Ph.D., Biology, University of California, San Diego, 2000

Professional Experience

2005-present Assistant Professor, The Scripps Research Institute, La Jolla, CA
2000-2004 Postdoctoral Fellow with Dr. Laurie Glimcher at Harvard School of Public Health
1996-2000 Graduate Student with Dr. Michael David at UCSD

Awards & Professional Activities

Other Experience and Professional Memberships

1999- The International Society of Interferon and Cytokine Research
2003-05 National Postdoctoral Association
2003- Association for Women in Science
2003- American Association of Immunologists

Grant Review: Arthritis Foundation (Molecular Immunology Study Section), Wellcome Trust, Swiss National Science Foundation

Ad hoc Reviewer: Journal of Immunology, Proceedings of the National Academy of Sciences, Journal of Biological Chemistry, Gene, FEBS Letters, Genes and Development, Developmental Cell, Nature Immunology

Honors

2005 The Hulda Irene Duggan Arthritis Investigator, Arthritis Foundation
2008 Donald and Delia Baxter Foundation Young Career Scientist Award

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.

Fathman J.W., Gurish M.F., Hemmers S., Bonham K., Friend D.S., Grusby M.J., Glimcher L.H, and Mowen K. A. (Feb 2010)  NIP45 Controls the Magnitude of the Type 2 T Helper Cell Response.  Proc Natl Acad Sci.  107:3663-8. PMCID: PMC2840445

Bonham K., Hemmers S., Lim Y-H., Hill D.H., Finn M.G., and Mowen K.A. (May 2010). Effects of a Novel Arginine Methyltransferase Inhibitor on T Helper Cell Cytokine Production. Febs Journal. 277:2096-108. PMCID: PMC2903848

Arandjelovic S., Leming S., and Mowen K. A. (epub Jul 2010). Coronin-1 is not required for mast degranulation. Journal of Leukoc Biol  PCMID: in progress.

Weerapana E., Wang C., Simon G.M., Khare S., Richter F., Dillon M.B.D., Bachovchin D.A., Mowen K.A., Baker D., and Cravatt B.F. (in press Nature) Quantitative reactivity profiling predicts functional cysteines in native and designed proteins.