Lucille P. Markey Charitable Trust

sponsor of

Basic and Clinical Research Career Tracks in Internal Medicine at

Columbia-Presbyterian Medical Center

Research Interests

The role cytokine signal transduction plays in innate and adaptive immunity with a focus on the JAK-STAT pathway.

Research Activities

Characterization of the ability of Interferons (IFNs), which are members of the cytokine/interleukin family, to rapidly induce new genes led to the identification of the JAK-STAT signaling pathway. Subsequent studies determined that there are four JAKs (Janus Kinases) and seven STATs (Signal Transducers and Activators of Transcription) that transduce pivotal signals for at least 50 other members of the cytokine/interleukin family. Current interests in the laboratory include studies on both the molecular details of STAT dependent signaling, as well as the important role STATs play in transducing the biological response to a number cytokines (e.g., IFNs, IL-4, IL-5, IL-6, IL-10, IL-12). For the latter studies, the laboratory exploits murine models of innate and adaptive immune response. This includes animal models of models of asthma, atherosclerosis, infectious disease and cancer.

Selected Publications

1. Schindler, C., Shuai, K., Prezioso, V., Darnell, JE. (1992). Interferon-dependent tyrosine phosphorylation of a latent cytoplasmic transcription factor. Science 257, 809-813.

2. Gupta, S., Pablo, AM., Jiang, X-c., Wang, N., Tall. AR., Schindler C. (1997). IFN-gamma potentiates atherosclerosis in apoE knock-out mice. J. Clin. Invest. 99, 2752-2761.

3. Azam, M., Lee, C., Strehlow, I., Schindler C. (1997). Functional distinct isoforms of Stat5 are generated by protein processing. Immunity 6, 691-701.

4. Collum, B., Brutsaert, S., Lee, G., Schindler C. (2000). A Stat3 Interacting Protein (StIP1) Regulates Cytokine Signal Transduction. Proc. Natl. Acad. Sci., USA. 97, 10120-10125.

5. Park, C., Li, S., Cha, E., Schindler, C. (2000) Immune response in Stat2 knock-out mice. Immunity 13, 795-804.

6. Song, L., Leung, C., Schindler, C. (2001). Lymphocytes are important in atherosclerosis. J. Clin. Invest., 108, 251-259.

7. Battacharya, S. & Schindler, C. (2003) Regulation of Stat3 nuclear export. J. Clin. Invest. 111, 553-559.

8. Braunstein, J., Brutsaert, S., Olson, R., Leung, C., Schindler, C. (2003) STATs dimerize in the absence of phosphorylation. J. Biol. Chem., In press.

Reviews

1. Kisseleva, T., Bhattacharya, S., Schröder-Braunstein, J., Schindler, C. (2002) Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene 285, 1-24.

2. Schindler, C. (2002) JAK-STAT signaling in human disease. J. Clin. Invest. 109, 1133-1137.