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Mowen, Kerri
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Mowen, Kerri

Faculty Member
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Positions

  • 2015 Associate Professor, Chemical Physiology , Scripps Research
  • 2007 - 2015 Assistant Professor, Chemical Physiology , Scripps Research
  • 2005 - 2015 Faculty Member, Skaggs Graduate School of Chemical and Biological Sciences , Scripps Research
  • 2005 - 2007 Assistant Professor, Immunology and Microbial Science (IMS) , Scripps Research
  • 2000 - 2004 Postdoctoral Fellow with Dr. Laurie H. Glimcher, School of Public Health, Harvard University
Dr. Kerri Mowen investigates the molecular events which control T helper cell and mast cell function, specifically studying a role for the posttranslational modification of arginine methylation by isolating novel substrates, determining the effects of arginine methylation on substrate function, and creating mice deficient in the enzymes that regulate arginine methylation.
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Publications

recent publications

  • academic article

    • Cheung, N., Fung, T. K., Zeisig, B. B., Holmes, K., Rane, J. K., Mowen, K. A., Finn, M. G., Lenhard, B., Chan, L. C., So, C. W. E. Targeting aberrant epigenetic networks mediated by PRMT1 and KDM4C in acute myeloid leukemia Cancer Cell  2016 29:32  DOI:10.1016/j.ccell.2015.12.007  PMID:26766589  PMCID:PMC4712026
    • Kolaczkowska, E., Jenne, C. N., Surewaard, B. G. J., Thanabalasuriar, A., Lee, W. Y., Sanz, M. J., Mowen, K., Opdenakker, G., Kubes, P. Molecular mechanisms of NET formation and degradation revealed by intravital imaging in the liver vasculature Nature Communications  2015 6:6673  DOI:10.1038/ncomms7673  PMID:25809117  PMCID:PMC4389265
    • Mowen, K. A., David, M. Unconventional post-translational modifications in immunological signaling Nature Immunology  2014 15:512-520  DOI:10.1038/ni.2873  PMID:24840982
    • Christophorou, M. A., Castelo-Branco, G., Halley-Stott, R. P., Oliveira, C. S., Loos, R., Radzisheuskaya, A., Mowen, K. A., Bertone, P., Silva, J. C. R., Zernicka-Goetz, M., Nielsen, M. L., Gurdon, J. B., et al. Citrullination regulates pluripotency and histone H1 binding to chromatin Nature  2014 507:104-108  DOI:10.1038/nature12942  PMID:24463520  PMCID:PMC4843970
    • MacLeod, A. S., Hemmers, S., Garijo, O., Chabod, M., Mowen, K., Witherden, D. A., Havran, W. L. Dendritic epidermal T cells regulate skin antimicrobial barrier function Journal of Clinical Investigation  2013 123:4364-4374  DOI:10.1172/jci70064  PMID:24051381  PMCID:PMC3784546
    • Fernandez-Castaneda, A., Arandjelovic, S., Stiles, T. L., Schlobach, R. K., Mowen, K. A., Gonias, S. L., Gaultier, A. Identification of the low density lipoprotein (ldl) receptor-related protein-1 interactome in central nervous system myelin suggests a role in the clearance of necrotic cell debris Journal of Biological Chemistry  2013 288:4538-4548  DOI:10.1074/jbc.M112.384693  PMID:23264627  PMCID:PMC3576060
    • Dillon, M. B., Rust, H. L., Thompson, P. R., Mowen, K. A. Automethylation of protein arginine methyltransferase 8 (PRMT8) regulates activity by impeding S-adenosylmethionine sensitivity Journal of Biological Chemistry  2013 288:27872-27880  DOI:10.1074/jbc.M113.491092  PMID:23946480  PMCID:PMC3784702
    • Arandjelovic, S., McKenney, K. R., Leming, S. S., Mowen, K. A. ATP induces protein arginine deiminase 2-dependent citrullination in mast cells through the P2X7 purinergic receptor Journal of Immunology  2012 189:4112-4122  DOI:10.4049/jimmunol.1201098  PMID:22984079  PMCID:PMC3466374
    • Dillon, M. B. C., Bachovchin, D. A., Brown, S. J., Finn, M. G., Rosen, H., Cravatt, B. F., Mowen, K. A. Novel inhibitors for PRMT1 discovered by high-throughput screening using activity-based fluorescence polarization ACS Chemical Biology  2012 7:1198-1204  DOI:10.1021/cb300024c  PMID:22506763  PMCID:PMC3401332
    • Rohrbach, A. S., Slade, D. J., Thompson, P. R., Mowen, K. A. Activation of PAD4 in NET formation Frontiers in Immunology  2012 3:360  DOI:10.3389/fimmu.2012.00360  PMID:23264775  PMCID:PMC3525017
    • Rohrbach, A. S., Hemmers, S., Arandjelovic, S., Corr, M., Mowen, K. A. PAD4 is not essential for disease in the K/BxN murine autoantibody-mediated model of arthritis Arthritis Research & Therapy  2012 14:R104  DOI:10.1186/ar3829  PMID:22551352  PMCID:PMC3446481
    • Hemmers, S., Teijaro, J. R., Arandjelovic, S., Mowen, K. A. PAD4-mediated neutrophil extracellular trap formation is not required for immunity against influenza infection PLoS One  2011 6:e22043  DOI:10.1371/journal.pone.0022043  PMID:21779371  PMCID:PMC3133614
    • Weerapana, E., Wang, C., Simon, G. M., Richter, F., Khare, S., Dillon, M. B. D., Bachovchin, D. A., Mowen, K., Baker, D., Cravatt, B. F. Quantitative reactivity profiling predicts functional cysteines in proteomes Nature  2010 468:790-795  DOI:10.1038/nature09472  PMID:21085121  PMCID:PMC3058684
    • Arandjelovic, S., Wickramarachchi, D., Hemmers, S., Leming, S. S., Kono, D. H., Mowen, K. A. Mast cell function is not altered by Coronin-1A deficiency Journal of Leukocyte Biology  2010 88:737-745  DOI:10.1189/jlb.0310131  PMID:20643816  PMCID:PMC2974433
    • Bonham, K., Hemmers, S., Lim, Y. H., Hill, D. M., Finn, M. G., Mowen, K. A. Effects of a novel arginine methyltransferase inhibitor on T-helper cell cytokine production FEBS Journal  2010 277:2096-2108  DOI:10.1111/j.1742-4658.2010.07623.x  PMID:20345902  PMCID:PMC2903848
    • Fathman, J. W., Gurish, M. F., Hemmers, S., Bonham, K., Friend, D. S., Grusby, M. J., Glimcher, L. H., Mowen, K. A. NIP45 controls the magnitude of the type 2 T helper cell response Proceedings of the National Academy of Sciences of the United States of America  2010 107:3663-3668  DOI:10.1073/pnas.0914700107  PMID:20133688  PMCID:PMC2840445
    • Hemmers, S., Mowen, K. A. T(H)2 bias: Mina tips the balance Nature Immunology  2009 10:806-808  DOI:10.1038/ni0809-806  PMID:19621039
    • Mowen, K. A., Glimcher, L. H. Signaling pathways in Th2 development Immunological Reviews  2004 202:203-222  DOI:10.1111/j.0105-2896.2004.00209.x  PMID:15546395
    • Mowen, K., David, M. Response to Matters Arising Cell  2004 119:589-590  DOI:10.1016/j.cell.2004.11.019
    • Mowen, K. A., Schurter, B. T., Fathman, J. W., David, M., Glimcher, L. H. Arginine methylation of NIP45 modulates cytokine gene expression in effector T lymphocytes Molecular Cell  2004 15:559-571  DOI:10.1016/j.molcel.2004.06.042  PMID:15327772
    • Rengarajan, J., Mowen, K. A., McBride, K. D., Smith, E. D., Singh, H., Glimcher, L. H. Interferon regulatory factor 4 (IRF4) interacts with NFATc2 to modulate interleukin 4 gene expression Journal of Experimental Medicine  2002 195:1003-1012  DOI:10.1084/jem.20011128  PMID:11956291  PMCID:PMC2193700
    • Blesofsky, W. A., Mowen, K., Arduini, R. M., Baker, D. P., Murphy, M. A., Bowtell, D. D. L., David, M. Regulation of STAT protein synthesis by c-Cbl Oncogene  2001 20:7326-7333  DOI:10.1038/sj.onc.1204919  PMID:11704862
    • Lieberson, R., Mowen, K. A., McBride, K. D., Leautaud, V., Zhang, X. K., Suh, W. K., Wu, L., Glimcher, L. H. Tumor necrosis factor receptor-associated factor (TRAF)2 represses the T helper cell type 2 response through interaction with NFAT-interacting protein (NIP45) Journal of Experimental Medicine  2001 194:89-98  DOI:10.1084/jem.194.1.89  PMID:11435475  PMCID:PMC2193447
    • Mowen, K. A., Tang, J., Zhu, W., Schurter, B. T., Shuai, K., Herschman, H. R., David, M. Arginine methylation of STAT1 modulates IFN alpha/beta-induced transcription Cell  2001 104:731-741  DOI:10.1016/s0092-8674(01)00269-0  PMID:11257227
    • Mowen, K. A., David, M. Analysis of protein arginine methylation and protein arginine-methyltransferase activity Science's STKE : Signal Transduction Knowledge Environment  2001 2001:pl1  DOI:10.1126/stke.2001.93.pl1  PMID:11752667
    • Mowen, K. A., David, M. Cytokine activation of transcription Genetic Engineering  2001 23:35-44  PMID:11570105
    • Mowen, K., David, M. Regulation of STAT1 nuclear export by Jak1 Molecular and Cellular Biology  2000 20:7273-7281  DOI:10.1128/mcb.20.19.7273-7281.2000  PMID:10982844  PMCID:PMC86281
    • Mowen, K., David, M. Role of the STAT1-SH2 domain and STATE in the activation and nuclear translocation of STAT1 Journal of Biological Chemistry  1998 273:30073-30076  DOI:10.1074/jbc.273.46.30073  PMID:9804758
    • Huggenvik, J. I., Michelson, R. J., Collard, M. W., Ziemba, A. J., Gurley, P., Mowen, K. A. Characterization of a nuclear deformed epidermal autoregulatory factor-1 (DEAF-1)-related (NUDR) transcriptional regulator protein Molecular Endocrinology  1998 12:1619-1639  DOI:10.1210/me.12.10.1619  PMID:9773984
    • Navarro, L., Mowen, K., Rodems, S., Weaver, B., Reich, N., Spector, D., David, M. Cytomegalovirus activates interferon immediate-early response gene expression and an interferon regulatory factor 3-containing interferon-stimulated response element-binding complex Molecular and Cellular Biology  1998 18:3796-3802  PMID:9632763  PMCID:PMC108963
  • thesis

    • Mowen, K. A. Interferon regulation of STAT1 nuclear localization and arginine methylation 2000

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Research

research overview

  • 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.

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Teaching

advisees

  • graduate advising relationship

    • Dillon, Myles, Ph.D.  candidate, 2009 - 2013
    • Rohrbach, Amanda, Ph.D.  candidate, 2007 - 2012
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Service

professional service activities

  • Arthritis Foundation Grant Review (Molecular Immunology Study Section) 2010 -
  • Swiss National Science Foundation Grant Review 2010 -
  • Wellcome Trust Grant Review 2010 -
  • Association for Women in Science Member 2003 -
  • The American Association of Immunologists Member 2003 -
  • International Society of Interferon and Cytokine Research Member 1999 -
  • National Postdoctoral Association Member 2003 - 2005
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Background

education and training

  • Ph.D. in Biology, University of California, San Diego , with Dr. Michael David 2000
  • B.A. in Biological Sciences, Southern Illinois University , summa cum laude 1996

awards and honors

  • Young Career Scientist Award, Donald and Delia Baxter Foundation, 2008
  • Hulda Irene Duggan Investigator Award, Arthritis Foundation, 2005
  • Travel Award, Federation of Clinical Immunology Societies, 2004
  • Teaching Assistant Award, Biology Department, University of California, San Diego, 1998
  • NIH Travel Award, Signal Transduction by Jaks and STATs, Keystone Symposia on Molecular and Cellular Biology, 1998
  • Honorable Mention, Howard Hughes Medical Institute Predoctoral Fellowship, 1997
  • Graduate Fellow, Lucille P. Markey Doctoral Fellowship (1996-1998)
  • Research Training Grant, Center for Molecular Genetics, University of California, San Diego (1998-1999)
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Contact

full name

  • Kerri A. Mowen

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