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1. Design principles for cyclin K molecular glue degraders

Author

Kozicka, Zuzanna, Suchyta, Dakota J., Focht, Vivian, Kempf, Georg, Petzold, Georg, Jentzsch, Marius, Zou, Charles, Di Genua, Cristina, Donovan, Katherine A., Coomar, Seemon, Cigler, Marko, Mayor-Ruiz, Cristina, Schmid-Burgk, Jonathan L., Häussinger, Daniel, Winter, Georg E., Fischer, Eric S., Słabicki, Mikołaj, Gillingham, Dennis, Ebert, Benjamin L., and Thomä, Nicolas H.

Published
2024
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3. IKKβ primes inflammasome formation by recruiting NLRP3 to the trans-Golgi network

Author

Schmacke, Niklas A., O’Duill, Fionan, Gaidt, Moritz M., Szymanska, Inga, Kamper, Julia M., Schmid-Burgk, Jonathan L., Mädler, Sophia C., Mackens-Kiani, Timur, Kozaki, Tatsuya, Chauhan, Dhruv, Nagl, Dennis, Stafford, Che A., Harz, Hartmann, Fröhlich, Adrian L., Pinci, Francesca, Ginhoux, Florent, Beckmann, Roland, Mann, Matthias, Leonhardt, Heinrich, and Hornung, Veit

Published
2022
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4. LAMP-Seq enables sensitive, multiplexed COVID-19 diagnostics using molecular barcoding

Author

Ludwig, Kerstin U., Schmithausen, Ricarda M., Li, David, Jacobs, Max L., Hollstein, Ronja, Blumenstock, Katja, Liebing, Jana, Słabicki, Mikołaj, Ben-Shmuel, Amir, Israeli, Ofir, Weiss, Shay, Ebert, Thomas S., Paran, Nir, Rüdiger, Wibke, Wilbring, Gero, Feldman, David, Lippke, Bärbel, Ishorst, Nina, Hochfeld, Lara M., Beins, Eva C., Kaltheuner, Ines H., Schmitz, Maximilian, Wöhler, Aliona, Döhla, Manuel, Sib, Esther, Jentzsch, Marius, Borrajo, Jacob D., Strecker, Jonathan, Reinhardt, Julia, Cleary, Brian, Geyer, Matthias, Hölzel, Michael, Macrae, Rhiannon, Nöthen, Markus M., Hoffmann, Per, Exner, Martin, Regev, Aviv, Zhang, Feng, and Schmid-Burgk, Jonathan L.

Published
2021
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6. Author Correction: LAMP-Seq enables sensitive, multiplexed COVID-19 diagnostics using molecular barcoding

Author

Ludwig, Kerstin U., Schmithausen, Ricarda M., Li, David, Jacobs, Max L., Hollstein, Ronja, Blumenstock, Katja, Liebing, Jana, Słabicki, Mikołaj, Ben-Shmuel, Amir, Israeli, Ofir, Weiss, Shay, Ebert, Thomas S., Paran, Nir, Rüdiger, Wibke, Wilbring, Gero, Feldman, David, Lippke, Bärbel, Ishorst, Nina, Hochfeld, Lara M., Beins, Eva C., Kaltheuner, Ines H., Schmitz, Maximilian, Wöhler, Aliona, Döhla, Manuel, Sib, Esther, Jentzsch, Marius, Moench, Eva-Maria C., Borrajo, Jacob D., Strecker, Jonathan, Reinhardt, Julia, Cleary, Brian, Geyer, Matthias, Hölzel, Michael, Macrae, Rhiannon, Nöthen, Markus M., Hoffmann, Per, Exner, Martin, Regev, Aviv, Zhang, Feng, and Schmid-Burgk, Jonathan L.

Published
2022
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8. Table S6 from MAPK Signaling and Inflammation Link Melanoma Phenotype Switching to Induction of CD73 during Immunotherapy

Author

Reinhardt, Julia, primary, Landsberg, Jennifer, primary, Schmid-Burgk, Jonathan L., primary, Ramis, Bartomeu Bibiloni, primary, Bald, Tobias, primary, Glodde, Nicole, primary, Lopez-Ramos, Dorys, primary, Young, Arabella, primary, Ngiow, Shin Foong, primary, Nettersheim, Daniel, primary, Schorle, Hubert, primary, Quast, Thomas, primary, Kolanus, Waldemar, primary, Schadendorf, Dirk, primary, Long, Georgina V., primary, Madore, Jason, primary, Scolyer, Richard A., primary, Ribas, Antoni, primary, Smyth, Mark J., primary, Tumeh, Paul C., primary, Tüting, Thomas, primary, and Hölzel, Michael, primary

Published
2023
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9. Tables S1, S2, S4, S8, S9 from MAPK Signaling and Inflammation Link Melanoma Phenotype Switching to Induction of CD73 during Immunotherapy

Author

Reinhardt, Julia, primary, Landsberg, Jennifer, primary, Schmid-Burgk, Jonathan L., primary, Ramis, Bartomeu Bibiloni, primary, Bald, Tobias, primary, Glodde, Nicole, primary, Lopez-Ramos, Dorys, primary, Young, Arabella, primary, Ngiow, Shin Foong, primary, Nettersheim, Daniel, primary, Schorle, Hubert, primary, Quast, Thomas, primary, Kolanus, Waldemar, primary, Schadendorf, Dirk, primary, Long, Georgina V., primary, Madore, Jason, primary, Scolyer, Richard A., primary, Ribas, Antoni, primary, Smyth, Mark J., primary, Tumeh, Paul C., primary, Tüting, Thomas, primary, and Hölzel, Michael, primary

Published
2023
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10. Legends to Suppl. Figures from MAPK Signaling and Inflammation Link Melanoma Phenotype Switching to Induction of CD73 during Immunotherapy

Author

Reinhardt, Julia, primary, Landsberg, Jennifer, primary, Schmid-Burgk, Jonathan L., primary, Ramis, Bartomeu Bibiloni, primary, Bald, Tobias, primary, Glodde, Nicole, primary, Lopez-Ramos, Dorys, primary, Young, Arabella, primary, Ngiow, Shin Foong, primary, Nettersheim, Daniel, primary, Schorle, Hubert, primary, Quast, Thomas, primary, Kolanus, Waldemar, primary, Schadendorf, Dirk, primary, Long, Georgina V., primary, Madore, Jason, primary, Scolyer, Richard A., primary, Ribas, Antoni, primary, Smyth, Mark J., primary, Tumeh, Paul C., primary, Tüting, Thomas, primary, and Hölzel, Michael, primary

Published
2023
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11. Supplementary Figure 1 to 7 from MAPK Signaling and Inflammation Link Melanoma Phenotype Switching to Induction of CD73 during Immunotherapy

Author

Reinhardt, Julia, primary, Landsberg, Jennifer, primary, Schmid-Burgk, Jonathan L., primary, Ramis, Bartomeu Bibiloni, primary, Bald, Tobias, primary, Glodde, Nicole, primary, Lopez-Ramos, Dorys, primary, Young, Arabella, primary, Ngiow, Shin Foong, primary, Nettersheim, Daniel, primary, Schorle, Hubert, primary, Quast, Thomas, primary, Kolanus, Waldemar, primary, Schadendorf, Dirk, primary, Long, Georgina V., primary, Madore, Jason, primary, Scolyer, Richard A., primary, Ribas, Antoni, primary, Smyth, Mark J., primary, Tumeh, Paul C., primary, Tüting, Thomas, primary, and Hölzel, Michael, primary

Published
2023
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12. Movie S2 from The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity against Acute Lymphoblastic Leukemia

Author

Vercruysse, Thomas, primary, De Bie, Jolien, primary, Neggers, Jasper E., primary, Jacquemyn, Maarten, primary, Vanstreels, Els, primary, Schmid-Burgk, Jonathan L., primary, Hornung, Veit, primary, Baloglu, Erkan, primary, Landesman, Yosef, primary, Senapedis, William, primary, Shacham, Sharon, primary, Dagklis, Antonis, primary, Cools, Jan, primary, and Daelemans, Dirk, primary

Published
2023
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13. Supplementary Methods from MAPK Signaling and Inflammation Link Melanoma Phenotype Switching to Induction of CD73 during Immunotherapy

Author

Reinhardt, Julia, primary, Landsberg, Jennifer, primary, Schmid-Burgk, Jonathan L., primary, Ramis, Bartomeu Bibiloni, primary, Bald, Tobias, primary, Glodde, Nicole, primary, Lopez-Ramos, Dorys, primary, Young, Arabella, primary, Ngiow, Shin Foong, primary, Nettersheim, Daniel, primary, Schorle, Hubert, primary, Quast, Thomas, primary, Kolanus, Waldemar, primary, Schadendorf, Dirk, primary, Long, Georgina V., primary, Madore, Jason, primary, Scolyer, Richard A., primary, Ribas, Antoni, primary, Smyth, Mark J., primary, Tumeh, Paul C., primary, Tüting, Thomas, primary, and Hölzel, Michael, primary

Published
2023
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14. Antiviral signalling by a cyclic nucleotide activated CRISPR protease

Author

Rouillon, Christophe, primary, Schneberger, Niels, additional, Chi, Haotian, additional, Blumenstock, Katja, additional, Da Vela, Stefano, additional, Ackermann, Katrin, additional, Moecking, Jonas, additional, Peter, Martin F., additional, Boenigk, Wolfgang, additional, Seifert, Reinhard, additional, Bode, Bela E., additional, Schmid-Burgk, Jonathan L., additional, Svergun, Dmitri, additional, Geyer, Matthias, additional, White, Malcolm F., additional, and Hagelueken, Gregor, additional

Published
2022
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15. Myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cells

Author

Armbruster, Julia, primary, Aboouf, Mostafa A., additional, Gassmann, Max, additional, Egert, Angela, additional, Schorle, Hubert, additional, Hornung, Veit, additional, Schmidt, Tobias, additional, Schmid-Burgk, Jonathan L., additional, Kristiansen, Glen, additional, Bicker, Anne, additional, Hankeln, Thomas, additional, Zhu, Hao, additional, and Gorr, Thomas A., additional

Published
2022
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16. Myoglobin regulates fatty acid trafficking and lipid metabolism in mammary epithelial cells

Author

Appanna, Vasu D, Appanna, V D ( Vasu D ), Armbruster, Julia, Aboouf, Mostafa A; https://orcid.org/0000-0003-0377-5939, Gassmann, Max, Egert, Angela, Schorle, Hubert; https://orcid.org/0000-0001-8272-0076, Hornung, Veit, Schmidt, Tobias, Schmid-Burgk, Jonathan L, Kristiansen, Glen, Bicker, Anne, Hankeln, Thomas, Zhu, Hao; https://orcid.org/0000-0003-0866-9246, Gorr, Thomas A; https://orcid.org/0000-0002-6023-4234, Appanna, Vasu D, Appanna, V D ( Vasu D ), Armbruster, Julia, Aboouf, Mostafa A; https://orcid.org/0000-0003-0377-5939, Gassmann, Max, Egert, Angela, Schorle, Hubert; https://orcid.org/0000-0001-8272-0076, Hornung, Veit, Schmidt, Tobias, Schmid-Burgk, Jonathan L, Kristiansen, Glen, Bicker, Anne, Hankeln, Thomas, Zhu, Hao; https://orcid.org/0000-0003-0866-9246, and Gorr, Thomas A; https://orcid.org/0000-0002-6023-4234

Abstract

Myoglobin (MB) is known to bind and deliver oxygen in striated muscles at high expression levels. MB is also expressed at much reduced levels in mammary epithelial cells, where the protein´s function is unclear. In this study, we aim to determine whether MB impacts fatty acid trafficking and facilitates aerobic fatty acid ß-oxidation in mammary epithelial cells. We utilized MB-wildtype versus MB-knockout mice and human breast cancer cells to examine the impact of MB and its oxygenation status on fatty acid metabolism in mouse milk and mammary epithelia. MB deficient cells were generated through CRISPR/Cas9 and TALEN approaches and exposed to various oxygen tensions. Fatty acid profiling of milk and cell extracts were performed along with cell labelling and immunocytochemistry. Our findings show that MB expression in mammary epithelial cells promoted fatty acid oxidation while reducing stearyl-CoA desaturase activity for lipogenesis. In cells and milk product, presence of oxygenated MB significantly elevated indices of limited fatty acid ß-oxidation, i.e., the organelle-bound removal of a C2 moiety from long-chain saturated or monounsaturated fatty acids, thus shifting the composition toward more saturated and shorter fatty acid species. Presence of the globin also increased cytoplasmic fatty acid solubility under normoxia and fatty acid deposition to lipid droplets under severe hypoxia. We conclude that MB can function in mammary epithelia as intracellular O$_{2}$-dependent shuttle of oxidizable fatty acid substrates. MB’s impact on limited oxidation of fatty acids could generate inflammatory mediator lipokines, such as 7-hexadecenoate. Thus, the novel functions of MB in breast epithelia described herein range from controlling fatty acid turnover and homeostasis to influencing inflammatory signalling cascade. Future work is needed to analyse to what extent these novel roles of MB also apply to myocytic cell physiology and malignant cell behaviour, respectively.

Published
2022

19. A Conserved Histidine in the RNA Sensor RIG-I Controls Immune Tolerance to N1-2′O-Methylated Self RNA

Author

Schuberth-Wagner, Christine, Ludwig, Janos, Bruder, Ann Kristin, Herzner, Anna-Maria, Zillinger, Thomas, Goldeck, Marion, Schmidt, Tobias, Schmid-Burgk, Jonathan L., Kerber, Romy, Wolter, Steven, Stümpel, Jan-Philip, Roth, Andreas, Bartok, Eva, Drosten, Christian, Coch, Christoph, Hornung, Veit, Barchet, Winfried, Kümmerer, Beate M., Hartmann, Gunther, and Schlee, Martin

Published
2015
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20. LAMP-Seq: Sensitive, Scalable, and Multiplexable COVID-19 Diagnostics Using Molecular Barcoding

Author

Ludwig, Kerstin U., Schmithausen, Ricarda M., Li, David, Jacobs, Max L., Hollstein, Ronja, Blumenstock, Katja, Liebing, Jana, Słabicki, Mikołaj, Ben-Shmuel, Amir, Israeli, Ofir, Weiss, Shay, Ebert, Thomas S., Paran, Nir, Rüdiger, Wibke, Wilbring, Gero, Feldman, David, Lippke, Bärbel, Ishorst, Nina, Hochfeld, Lara M., Beins, Eva C., Kaltheuner, Ines H., Schmitz, Maximilian, Wöhler, Aliona, Döhla, Manuel, Sib, Esther, Jentzsch, Marius, Borrajo, Jacob D., Strecker, Jonathan, Reinhardt, Julia, Cleary, Brian, Geyer, Matthias, Hölzel, Michael, Macrae, Rhiannon, Nöthen, Markus M., Hoffmann, Per, Exner, Martin, Regev, Aviv, Zhang, Feng, and Schmid-Burgk, Jonathan L.

Subjects
Article
Abstract

Frequent testing of large population groups combined with contact tracing and isolation measures will be crucial for containing COVID-19 outbreaks. Here, we present LAMP-Seq, a modified, highly scalable reverse-transcription loop-mediated isothermal amplification (RT-LAMP) method. Unpurified biosamples are barcoded and amplified in a single heat step, and pooled products are analyzed en masse by sequencing. Using commercial reagents, LAMP-Seq has a limit of detection of ~2.2 molecules/µl at 95% confidence, and near-perfect specificity for SARS-CoV-2 given its sequence readout. Clinical validation of an open-source protocol with 676 swab samples, 98 of which were deemed positive by standard RT-qPCR, demonstrated 100% sensitivity in individuals with Ct values up to 33, and a specificity of 99.7%, at material cost of 2.73 USD per sample. With a time-to-result less than 24 hours, low cost, and little new infrastructure requirement, LAMP-Seq can be readily deployed for frequent testing as part of an integrated public health surveillance program.

Published
2021

21. Cell intrinsic immunity spreads to bystander cells via the intercellular transfer of cGAMP

Author

Ablasser, Andrea, Schmid-Burgk, Jonathan L., Hemmerling, Inga, Horvath, Gabor L., Schmidt, Tobias, Latz, Eicke, and Hornung, Veit

Subjects
Cellular immunity -- Research, Cyclic adenylic acid -- Properties, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

The innate immune defence of multicellular organisms against microbial pathogens requires cellular collaboration. Information exchange allowing immune cells to collaborate is generally attributed to soluble protein factors secreted by pathogen-sensing cells. Cytokines, such as type I interferons (IFNs), serve to alert non-infected cells to the possibility of pathogen challenge (1). Moreover, in conjunction with chemokines they can instruct specialized immune cells to contain and eradicate microbial infection. Several receptors and signalling pathways exist that couple pathogen sensing to the induction of cytokines, whereas cytosolic recognition of nucleic acids seems to be exquisitely important for the activation of type I IFNs, master regulators of antiviral immunity (2). Cytosolic DNA is sensed by the receptor cyclic GMP-AMP (cGAMP) synthase (cGAS), which catalyses the synthesis of the second messenger cGAMP(2'-5') (3-8). This molecule in turn activates the endoplasmic reticulum (ER)-resident receptor STING (9-11), thereby inducing an antiviral state and the secretion of type I IFNs. Here we find in murine and human cells that cGAS-synthesized cGAMP (2'-5') is transferred from producing cells to neighbouring cells through gap junctions, where it promotes STING activation and thus antiviral immunity independently of type I IFN signalling. In line with the limited cargo specificity of connexins, the proteins that assemble gap junction channels, most connexins tested were able to confer this bystander immunity, thus indicating a broad physiological relevance of this local immune collaboration. Collectively, these observations identify cGAS-triggered cGAMP(2'-5') transfer as a novel host strategy that serves to rapidly convey antiviral immunity in a transcription-independent, horizontal manner., On recognition of virus-derived nucleic acids, innate immune signalling initiates cell-autonomous antiviral effector mechanisms that aim to block viral propagation. Moreover, virus-infected cells alert non-infected neighbouring cells, a process largely [...]

Published
2013

23. Diverse enzymatic activities mediate antiviral immunity in prokaryotes

Author

Howard Hughes Medical Institute, Massachusetts Institute of Technology. Department of Biological Engineering, McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Gao, Linyi, Altae-Tran, Han, Böhning, Francisca, Makarova, Kira S, Segel, Michael, Schmid-Burgk, Jonathan L, Koob, Jeremy, Wolf, Yuri I, Koonin, Eugene V, Zhang, Feng, Howard Hughes Medical Institute, Massachusetts Institute of Technology. Department of Biological Engineering, McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Gao, Linyi, Altae-Tran, Han, Böhning, Francisca, Makarova, Kira S, Segel, Michael, Schmid-Burgk, Jonathan L, Koob, Jeremy, Wolf, Yuri I, Koonin, Eugene V, and Zhang, Feng

Abstract

Bacteria and archaea are frequently attacked by viruses and other mobile genetic elements and rely on dedicated antiviral defense systems, such as restriction endonucleases and CRISPR, to survive. The enormous diversity of viruses suggests that more types of defense systems exist than are currently known. By systematic defense gene prediction and heterologous reconstitution, here we discover 29 widespread antiviral gene cassettes, collectively present in 32% of all sequenced bacterial and archaeal genomes, that mediate protection against specific bacteriophages. These systems incorporate enzymatic activities not previously implicated in antiviral defense, including RNA editing and retron satellite DNA synthesis. In addition, we computationally predict a diverse set of other putative defense genes that remain to be characterized. These results highlight an immense array of molecular functions that microbes use against viruses.

Published
2021

24. Design principles for cyclin K molecular glue degraders

Author

Kozicka, Zuzanna, Suchyta, Dakota J., Focht, Vivian, Kempf, Georg, Petzold, Georg, Jentzsch, Marius, Zou, Charles, Di Genua, Cristina, Donovan, Katherine A., Coomar, Seemon, Cigler, Marko, Mayor-Ruiz, Cristina, Schmid-Burgk, Jonathan L., Häussinger, Daniel, Winter, Georg E., Fischer, Eric S., Słabicki, Mikołaj, Gillingham, Dennis, Ebert, Benjamin L., and Thomä, Nicolas H.

Abstract

Molecular glue degraders are an effective therapeutic modality, but their design principles are not well understood. Recently, several unexpectedly diverse compounds were reported to deplete cyclin K by linking CDK12–cyclin K to the DDB1–CUL4–RBX1 E3 ligase. Here, to investigate how chemically dissimilar small molecules trigger cyclin K degradation, we evaluated 91 candidate degraders in structural, biophysical and cellular studies and reveal all compounds acquire glue activity via simultaneous CDK12 binding and engagement of DDB1 interfacial residues, in particular Arg928. While we identify multiple published kinase inhibitors as cryptic degraders, we also show that these glues do not require pronounced inhibitory properties for activity and that the relative degree of CDK12 inhibition versus cyclin K degradation is tuneable. We further demonstrate cyclin K degraders have transcriptional signatures distinct from CDK12 inhibitors, thereby offering unique therapeutic opportunities. The systematic structure–activity relationship analysis presented herein provides a conceptual framework for rational molecular glue design.

Published
2023
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25. LAMP-Seq: Population-Scale COVID-19 Diagnostics Using a Compressed Barcode Space

Author

Schmid-Burgk, Jonathan L., Li, David, Feldman, David, Słabicki, Mikołaj, Borrajo, Jacob, Strecker, Jonathan, Cleary, Brian, Regev, Aviv, and Zhang, Feng

Abstract

Summary The ongoing COVID-19 pandemic has already caused devastating losses. Early evidence shows that the exponential spread of COVID-19 can be slowed by restrictive isolation measures, but these place a tremendous burden on society. Moreover, once these restrictions are lifted, the exponential spread is likely to re-emerge. It has been suggested that population-scale testing can help break the cycle of isolation and spread, but current detection methods are not capable of such large-scale processing. Here we propose LAMP-Seq, a barcoded Reverse-Transcription Loop-mediated Isothermal Amplification (RT-LAMP) protocol that could dramatically reduce the cost and complexity of population-scale testing. In this approach, individual samples are processed in a single heat step, producing barcoded amplicons that can be shipped to a sequencing center, pooled, and analyzed en masse . Using unique barcode combinations per sample from a compressed barcode space enables extensive pooling, significantly reducing cost and organizational efforts. Given the low cost and scalability of next-generation sequencing, we believe that this method can be affordably scaled to analyze millions of samples per day using existing sequencing infrastructure.

Published
2020
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27. RNA-guided DNA insertion with CRISPR-associated transposases

Author

McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology. Department of Biological Engineering, Strecker, Jonathan, Ladha, Alim, Gardner, Zachary, Schmid-Burgk, Jonathan L., Makarova, Kira S., Koonin, Eugene V., Zhang, Feng, McGovern Institute for Brain Research at MIT, Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology. Department of Biological Engineering, Strecker, Jonathan, Ladha, Alim, Gardner, Zachary, Schmid-Burgk, Jonathan L., Makarova, Kira S., Koonin, Eugene V., and Zhang, Feng

Abstract

CRISPR-Cas nucleases are powerful tools for manipulating nucleic acids; however, targeted insertion of DNA remains a challenge, as it requires host cell repair machinery. Here we characterize a CRISPR-associated transposase from cyanobacteria Scytonema hofmanni (ShCAST) that consists of Tn7-like transposase subunits and the type V-K CRISPR effector (Cas12k). ShCAST catalyzes RNA-guided DNA transposition by unidirectionally inserting segments of DNA 60 to 66 base pairs downstream of the protospacer. ShCAST integrates DNA into targeted sites in the Escherichia coli genome with frequencies of up to 80% without positive selection. This work expands our understanding of the functional diversity of CRISPR-Cas systems and establishes a paradigm for precision DNA insertion., National Institutes of Health (Grant 1R01-HG009761), National Institutes of Health (Grant 1R01-MH110049), National Institutes of Health (Grant 1DP1-HL141201)

Published
2020

28. Structure-guided multivalent nanobodies block SARS-CoV-2 infection and suppress mutational escape

Author

Koenig, Paul-Albert, primary, Das, Hrishikesh, additional, Liu, Hejun, additional, Kümmerer, Beate M., additional, Gohr, Florian N., additional, Jenster, Lea-Marie, additional, Schiffelers, Lisa D. J., additional, Tesfamariam, Yonas M., additional, Uchima, Miki, additional, Wuerth, Jennifer D., additional, Gatterdam, Karl, additional, Ruetalo, Natalia, additional, Christensen, Maria H., additional, Fandrey, Caroline I., additional, Normann, Sabine, additional, Tödtmann, Jan M. P., additional, Pritzl, Steffen, additional, Hanke, Leo, additional, Boos, Jannik, additional, Yuan, Meng, additional, Zhu, Xueyong, additional, Schmid-Burgk, Jonathan L., additional, Kato, Hiroki, additional, Schindler, Michael, additional, Wilson, Ian A., additional, Geyer, Matthias, additional, Ludwig, Kerstin U., additional, Hällberg, B. Martin, additional, Wu, Nicholas C., additional, and Schmidt, Florian I., additional

Published
2021
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31. LAMP-Seq: Population-Scale COVID-19 Diagnostics Using Combinatorial Barcoding

Author

Schmid-Burgk, Jonathan L., primary, Schmithausen, Ricarda M., additional, Li, David, additional, Hollstein, Ronja, additional, Ben-Shmuel, Amir, additional, Israeli, Ofir, additional, Weiss, Shay, additional, Paran, Nir, additional, Wilbring, Gero, additional, Liebing, Jana, additional, Feldman, David, additional, Słabicki, Mikołaj, additional, Lippke, Bärbel, additional, Sib, Esther, additional, Borrajo, Jacob, additional, Strecker, Jonathan, additional, Reinhardt, Julia, additional, Hoffmann, Per, additional, Cleary, Brian, additional, Hölzel, Michael, additional, Nöthen, Markus M., additional, Exner, Martin, additional, Ludwig, Kerstin U., additional, Regev, Aviv, additional, and Zhang, Feng, additional

Published
2020
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32. Experimental and stochastic models of melanoma T-cell therapy define impact of subclone fitness on selection of antigen loss variants

Author

Glodde, Nicole, primary, Kraut, Anna, additional, van den Boorn-Konijnenberg, Debby, additional, Vadder, Saskia, additional, Kreten, Florian, additional, Schmid-Burgk, Jonathan L., additional, Aymans, Pia, additional, Echelmeyer, Kai, additional, Rumpf, Martin, additional, Landsberg, Jennifer, additional, Bald, Tobias, additional, Tüting, Thomas, additional, Bovier, Anton, additional, and Hölzel, Michael, additional

Published
2019
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33. Priming enables a NEK7-independent route of NLRP3 activation

Author

Schmacke, Niklas A., primary, Gaidt, Moritz M., additional, Szymanska, Inga, additional, O’Duill, Fionan, additional, Stafford, Che A., additional, Chauhan, Dhruv, additional, Fröhlich, Adrian L., additional, Nagl, Dennis, additional, Pinci, Francesca, additional, Schmid-Burgk, Jonathan L., additional, and Hornung, Veit, additional

Published
2019
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34. Optical Pooled Screens in Human Cells

Author

Feldman, David, primary, Singh, Avtar, additional, Schmid-Burgk, Jonathan L., additional, Carlson, Rebecca J., additional, Mezger, Anja, additional, Garrity, Anthony J., additional, Zhang, Feng, additional, and Blainey, Paul C., additional

Published
2019
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36. Pooled optical screens in human cells

Author

Feldman, David, primary, Singh, Avtar, additional, Schmid-Burgk, Jonathan L., additional, Mezger, Anja, additional, Garrity, Anthony J., additional, Carlson, Rebecca J., additional, Zhang, Feng, additional, and Blainey, Paul C., additional

Published
2018
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38. The DNA Inflammasome in Human Myeloid Cells Is Initiated by a STING-Cell Death Program Upstream of NLRP3

Author

Gaidt, Moritz M., primary, Ebert, Thomas S., additional, Chauhan, Dhruv, additional, Ramshorn, Katharina, additional, Pinci, Francesca, additional, Zuber, Sarah, additional, O’Duill, Fionan, additional, Schmid-Burgk, Jonathan L., additional, Hoss, Florian, additional, Buhmann, Raymund, additional, Wittmann, Georg, additional, Latz, Eicke, additional, Subklewe, Marion, additional, and Hornung, Veit, additional

Published
2017
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39. MAPK Signaling and Inflammation Link Melanoma Phenotype Switching to Induction of CD73 during Immunotherapy

Author

Reinhardt, Julia, primary, Landsberg, Jennifer, additional, Schmid-Burgk, Jonathan L., additional, Ramis, Bartomeu Bibiloni, additional, Bald, Tobias, additional, Glodde, Nicole, additional, Lopez-Ramos, Dorys, additional, Young, Arabella, additional, Ngiow, Shin Foong, additional, Nettersheim, Daniel, additional, Schorle, Hubert, additional, Quast, Thomas, additional, Kolanus, Waldemar, additional, Schadendorf, Dirk, additional, Long, Georgina V., additional, Madore, Jason, additional, Scolyer, Richard A., additional, Ribas, Antoni, additional, Smyth, Mark J., additional, Tumeh, Paul C., additional, Tüting, Thomas, additional, and Hölzel, Michael, additional

Published
2017
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40. The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity against Acute Lymphoblastic Leukemia

Author

Vercruysse, Thomas, primary, De Bie, Jolien, additional, Neggers, Jasper E., additional, Jacquemyn, Maarten, additional, Vanstreels, Els, additional, Schmid-Burgk, Jonathan L., additional, Hornung, Veit, additional, Baloglu, Erkan, additional, Landesman, Yosef, additional, Senapedis, William, additional, Shacham, Sharon, additional, Dagklis, Antonis, additional, Cools, Jan, additional, and Daelemans, Dirk, additional

Published
2017
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43. Mycobacterium tuberculosis Differentially Activates cGAS- and Inflammasome-Dependent Intracellular Immune Responses through ESX-1

Author

Wassermann, Ruth, Gulen, Muhammet F., Sala, Claudia, Perin, Sonia Garcia, Lou, Ye, Rybniker, Jan, Schmid-Burgk, Jonathan L., Schmidt, Tobias, Hornung, Veit, Cole, Stewart T., Ablasser, Andrea, Wassermann, Ruth, Gulen, Muhammet F., Sala, Claudia, Perin, Sonia Garcia, Lou, Ye, Rybniker, Jan, Schmid-Burgk, Jonathan L., Schmidt, Tobias, Hornung, Veit, Cole, Stewart T., and Ablasser, Andrea

Abstract

Cytosolic detection of microbial products is essential for the initiation of an innate immune response against intracellular pathogens such as Mycobacterium tuberculosis (Mtb). During Mtb infection of macrophages, activation of cytosolic surveillance pathways is dependent on the mycobacterial ESX-1 secretion system and leads to type I interferon (IFN) and interleukin-1 beta (IL-1 beta) production. Whereas the inflammasome regulates IL-1 beta secretion, the receptor(s) responsible for the activation of type I IFNs has remained elusive. We demonstrate that the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS) is essential for initiating an IFN response to Mtb infection. cGAS associates with Mtb DNA in the cytosol to stimulate cyclic GAMP (cGAMP) synthesis. Notably, activation of cGAS-dependent cytosolic host responses can be uncoupled from inflammasome activation by modulating the secretion of ESX-1 substrates. Our findings identify cGAS as an innate sensor of Mtb and provide insight into how ESX-1 controls the activation of specific intracellular recognition pathways.

Published
2015

47. Mycobacterium tuberculosis Differentially Activates cGAS- and Inflammasome-Dependent Intracellular Immune Responses through ESX-1

Author

Wassermann, Ruth, primary, Gulen, Muhammet F., additional, Sala, Claudia, additional, Perin, Sonia Garcia, additional, Lou, Ye, additional, Rybniker, Jan, additional, Schmid-Burgk, Jonathan L., additional, Schmidt, Tobias, additional, Hornung, Veit, additional, Cole, Stewart T., additional, and Ablasser, Andrea, additional

Published
2015
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48. ATP-Dependent Effector-like Functions of RIG-I-like Receptors

Author

Yao, Hui, primary, Dittmann, Meike, additional, Peisley, Alys, additional, Hoffmann, Hans-Heinrich, additional, Gilmore, Rachel H., additional, Schmidt, Tobias, additional, Schmid-Burgk, Jonathan L., additional, Hornung, Veit, additional, Rice, Charles M., additional, and Hur, Sun, additional

Published
2015
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49. Influenza Virus Adaptation PB2-627K Modulates Nucleocapsid Inhibition by the Pathogen Sensor RIG-I

Author

Weber, Michaela, primary, Sediri, Hanna, additional, Felgenhauer, Ulrike, additional, Binzen, Ina, additional, Bänfer, Sebastian, additional, Jacob, Ralf, additional, Brunotte, Linda, additional, García-Sastre, Adolfo, additional, Schmid-Burgk, Jonathan L., additional, Schmidt, Tobias, additional, Hornung, Veit, additional, Kochs, Georg, additional, Schwemmle, Martin, additional, Klenk, Hans-Dieter, additional, and Weber, Friedemann, additional

Published
2015
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50. Cutting Edge: The UNC93B1 Tyrosine-Based Motif Regulates Trafficking and TLR Responses via Separate Mechanisms

Author

Pelka, Karin, Phulphagar, Kshiti, Zimmermann, Jana, Stahl, Rainer, Schmid-Burgk, Jonathan L., Schmidt, Tobias, Spille, Jan-Hendrik, Labzin, Larisa I., Agrawal, Sudhir, Kandimalla, Ekambar R., Casanova, Jean-Laurent, Hornung, Veit, Marshak-Rothstein, Ann, Hoening, Stefan, Latz, Eicke, Pelka, Karin, Phulphagar, Kshiti, Zimmermann, Jana, Stahl, Rainer, Schmid-Burgk, Jonathan L., Schmidt, Tobias, Spille, Jan-Hendrik, Labzin, Larisa I., Agrawal, Sudhir, Kandimalla, Ekambar R., Casanova, Jean-Laurent, Hornung, Veit, Marshak-Rothstein, Ann, Hoening, Stefan, and Latz, Eicke

Abstract

Sensing of nucleic acids by TLRs is crucial in the host defense against viruses and bacteria. Unc-93 homolog B1 (UNC93B1) regulates the trafficking of nucleic acid-sensing TLRs from the endoplasmic reticulum to endolysosomes, where the TLRs encounter their respective ligands and become activated. In this article, we show that a carboxyl-terminal tyrosine-based sorting motif (Yxx Phi) in UNC93B1 differentially regulates human nucleic acid-sensing TLRs in a receptor-and ligand-specific manner. Destruction of YxxF abolished TLR7, TLR8, and TLR9 activity toward nucleic acids in human B cells and monocytes, whereas TLR8 responses toward small molecules remained intact. YxxF in UNC93B1 influenced the subcellular localization of human UNC93B1 via both adapter protein complex (AP)1- and AP2-dependent trafficking pathways. However, loss of AP function was not causal for altered TLR responses, suggesting AP-independent functions of YxxF in UNC93B1.

Published
2014

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