Breadcrumb

Jonathan D. Ashwell, M.D.

Jonathan D. Ashwell, M.D.

  • Center for Cancer Research
  • National Cancer Institute

RESEARCH SUMMARY

Dr. Ashwell's laboratory focused on the mechanisms and consequences of intracellular signaling, primarily in T cell. Among the major approaches taken to understand this important biological phenomenon were (1) characterization of the molecules and pathways involved in proximal T cell antigen receptor (TCR) signaling, (2) mechanisms and consequences of p38 activation in T cells via the ZAP-70-mediated "alternative pathway", and (3) studies of the biological importance of thymically-produced glucocorticoids in thymocyte antigen-specific selection and generation of the mature T cell repertoire.

Areas of Expertise

Cancer Immunology and Immunotherapy
Cancer Signaling and Pathways
p38
T-Cell Receptor
T-Cell Activation
Thymocyte Development

Publications

Selected Key Publications

Thymocyte responsiveness to endogenous glucocorticoids is required for immunological fitness

Mittelstadt PR, Monteiro JP, Ashwell JD.
J. Clin. Invest. 122: 2384-94, 2012. [ Journal Article ]

Counter-regulation of T cell effector function by differentially activated p38

Alam MS, Gaida MM, Ogawa Y, Kolios AG, Lasitschka F, Ashwell JD.
J. Exp. Med. 211: 1257-70, 2014. [ Journal Article ]

Selective inhibition of the p38 alternative activation pathway in infiltrating T cells inhibits pancreatic cancer progression

Alam, M. S., Gaida, M. M., Bergmann, F., Lasitschka, F., Giese, T., Giese, N. A., Hackert, T., Hinz, U., Hussain, S. P., Kozlov, S. V., and Ashwell, J. D
Nat. Med.. 21: 1337-1343, 2015. [ Journal Article ]

Activation-induced recruitment of calcineurin to the T cell receptor positively regulates proximal signaling and effector functions

Dutta, D., Barr, V. A., Akpan, I., Mittelstadt, P. R., Singha, L. I., Samelson, L. E., and Ashwell, J. D.
Nat. Immunol.. 18: 296-304, 2017.

Intensity and duration of TCR signaling is limited by p38 phosphorylation of ZAP-70T293 and destabilization of the signalosome

Torchia, M. L. G., Dutta, D., Mittelstadt, P. R., Guha, J., Gaida, M. M., Fish, K., Barr, V. A., Akpan, I. O., Samelson, L. E., Tagad, H. D., Debnath, S., Miller Jenkins, L. M., Appella, E., and Ashwell, J. D.
Proc. Natl. Acad. Sci. USA.. 115: 2174-2179, 2018. [ Journal Article ]