Structural Immuno-Oncology Research Group

Inflammation is an early response of our bodies to infection and danger. It is initiated by a set of specialized proteins called pattern-recognition receptors, which trigger downstream signaling and activate cell programs to clear the infection and repair the damaged tissue. While controlled inflammation protects us from pathogens, “mistakes” in its regulation emerging from mutations, environmental factors or our lifestyle leads to chronic inflammation – an underlying cause of numerous diseases hunting the modern society, including autoinflammation and cancer. 

Our group is interested in studying inflammatory pathways in health and disease on the molecular level. We combine various structural, biochemical, and cell-based approaches to decipher the mechanisms governing inflammation with an ultimate goal – to provide a foundation for development of novel anti-inflammatory and anti-cancer treatments.

NLRP3 cages revealed by full-length mouse NLRP3 structure control pathway activation.
Andreeva L., David L., Rawson S., Shen C., Pasricha T., Pelegrin P., and Wu H. (2021). Cell. 184(26):6299-6312.e6222. doi: 10.1016/j.cell.2021.11.011 

Phase separation drives RNA virus-induced activation of the NLRP6 inflammasome.
Shen C., Li R., Negro R., Cheng J., Vora S. M., Fu T.-M., Wang A., He K., Andreeva L., Gao P., Tian Z., Flavell R. A., Zhu S., and Wu H. (2021). Cell. 184(23):5759-5774.e20. doi: 10.1016/j.cell.2021.09.032 

BTK operates a phospho-tyrosine switch to regulate NLRP3 inflammasome activity.
Bittner Z.A., Liu X., Mateo Tortola M., Tapia-Abellán A., Shankar S., Andreeva L., Mangan M., Spalinger M., Kalbacher H., Düwell P., Lovotti M., Bosch K., Dickhöfer S., Marcu A., Stevanović S., Herster F., Cardona Gloria Y., Chang T.H., Bork F., Greve C.L., Löffler M.W., Wolz O.O., Schilling N.A., Kümmerle-Deschner J.B., Wagner S., Delor A., Grimbacher B., Hantschel O., Scharl M., Wu H., Latz E., and Weber A.N.R. (2021) J. Exp. Med. 218(11):e20201656. doi: 10.1084/jem.20201656 

STING condensates on ER limit IFN response.
Andreeva L. and Wu H. (2021). Nat. Cell Biol. 23(4):299-300. doi: 10.1038/s41556-021-00662-5  

The cytosolic DNA sensor cGAS recognizes neutrophil extracellular traps.
Apel F., Andreeva L., Knackstedt L.S., Streeck R., Frese C.K., Goosmann C., Hopfner K.-P., and Zychlinsky A. (2021). Sci. Signal. 4(673):eaax7942. doi: 10.1126/scisignal.aax7942 

Structural mechanism for NEK7-licensed activation of NLRP3 inflammasome.
Sharif H., Wang L., Wang W. L., Magupalli V. G., Andreeva L., Qiao Q., Hauenstein A. V., Wu Z., Núñez G., Mao Y., and Wu H. (2019). Nature 570(7761): 338-343. doi: 10.1038/s41586-019-1295-z 

cGAS senses long and HMGB/TFAM bound U-turn DNA by forming protein-DNA ladders.
Andreeva L., Hiller B., Kostrewa D., Lässig C., de Oliveira Mann C.C., Drexler D.J., Maiser A., Gaidt M., Leonhardt H., Hornung V., and Hopfner K.-P. (2017) Nature 549(7672): 394-398. doi: 10.1038/nature23890

Sequence-specific activation of the DNA sensor cGAS by Y-form DaTNA structures as found in primary HIV-1 cDNA.
Herzner A.M., Hagmann C.A., Goldeck M., Wolter S., Kübler K., Wittmann S., Gramberg T., Andreeva L., Hopfner K.-P., Mertens C., Zillinger T., Jin T., Xiao T.S., Bartok E., Coch C., Ackermann D., Hornung V., Ludwig J., Barchet W., Hartmann G., and Schlee M. (2015) Nat. Immunol. 16(10):1025-33. doi: 10.1038/ni.3267 

Cytosolic RNA:DNA hybrids activate the cGAS–STING axis.
Mankan A.K., Schmidt T., Chauhan D., Goldeck M., Höning K., Gaidt M., Kubarenko A.V., Andreeva L., Hopfner K.-P., and Hornung V. (2014) EMBO J. 33(24):2937-46. doi: 10.15252/embj.201488726