Christian Stehlik, PhD Assistant Professor Medicine, Division of Rheumatology Molecular mechanisms of inflammatory and infectious disease Curricula: Immunology and Microbial Pathogenesis Molecular Biology and Genetics E-mail:   c-stehlik@northwestern.edu

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The major focus in my laboratory is to delineate regulatory mechanisms of immunity and inflammation. In particular, we are studying inflammasomes, which are molecular platforms in phagocytic cells that mediate activation of inflammatory caspases and their cytokine substrates, interleukin (IL)-1 and IL-18. Defects in inflammasomes, such as hereditary mutations, are linked to human debilitating inflammatory diseases, and is caused by dysregulated signal transduction and excessive and inappropriate secretion of the inflammatory cytokines IL-1 and IL-18.

We identified several novel components of inflammasomes, including an activating receptor and a novel regulatory protein family, which we termed PYRIN-only proteins (POPs). Several additional mechanisms that limit inflammasome assembly and activity are currently under investigation, including inflammasome localization and posttranslational modification of inflammasome components.

The lab has also interest in the apoptotic response mediated by some inflammasome components in epithelial cells. In particular, ASC and POP1 are silenced by promoter methylation in carcinomas, such as breast cancer, suggesting a potential role as tumor suppressor genes. Molecular mechanisms by which these proteins mediate apoptosis are under investigation.

Finally, we are interested in a novel member of the adhesion family of G-proteincoupled receptors, and its function in the inflammatory response and activation of endothelial cells.

Selected Publications:

Stehlik, C., Krajewska, M., Welsh, K., Krajewski, S., Godzik, A., and Reed, J.C. (2003) The PAAD/PYRIN-only protein POP is a modulator of ASC-mediated NF-kB and pro-Caspase-1 regulation. Biochem. J. 372, 101-113.

Stehlik, C., Lee, S.H., Dorfleutner A., Stassinopoulos, A., Sagara, J., and Reed, J.C. (2003) Apoptosis-associated speck-like protein containing a caspase recruitment domain is a Regulator of pro-Caspase-1 Activation, J. Immunol. 171, 6154-63.

Stehlik, C. and Reed, J.C. (2004) The PYRIN Connection: Novel Players in innate immunity and inflammation. (Review) J. Exp. Med. 200, 551-558.

Stehlik C., Kroismayr, R., Dorfleutner A., Binder B.R., and Lipp J. (2004) VIGR – a novel inducible adhesion family G-protein coupled receptor in endothelial cells. FEBS Letters 569, 149-155.

Dorfleutner, A., Talbott, S.J., Bryan, N.B., Funya, K.N., Rellick, S.L., Reed, J.C., Shi, X., Flynn, D.C, Rojanasakul, Y. and Stehlik, C. (2007) A shope Fibroma virus PYRIN-only protein modulates the host immune response. Virus Genes, 35, 685-694.

Dorfleutner, A., Bryan, N.B., Talbott, S.J., Fynya, K.N., Rellick, S.L., Reed, J.C., Shi, X., Royanasakul, Y., Flynn, D.C., and Stehlik, C. (2007) Cellular PYRIN domain-only protein (cPOP) 2 is a novel regulator of inflammasome activation. Infect. Immun., 75, 1484-1492.

Stehlik, C. (2007) The PYRIN domain in signal transduction. Curr. Prot. Pept. Sci., 8, 293-310.

Stehlik, C. and Dorfleutner, A. (2007) COPs & POPs: Modulators of Inflammasome Activity. J. Immunol., 179, 7993-7998.

Bryan, N.B., Dorfleutner, A., Rojanasakul, Y, and Stehlik, C. (2009) Activation of inflammasomes requires intracellular redistribution of the apoptotic speck-like protein containing a caspase recruitment domain (ASC). J. Immunol., 182, 3173-3182.