SAT - Helmholtz Munich

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The Research Unit (RU) “Signaling and Translation” (SAT) investigates how key cellular signaling pathways control health and disease. Our aim is to understand how physiological signaling maintains homeostasis and triggers efficient responses to environmental changes or immune challenges. At the same time, we elucidate how defective or aberrant signaling pathways are contributing to autoimmunity, inflammation, or cell death, which can trigger human pathologies such as diabetes and cancer. We fill the gap between basic science and clinical innovations by providing direct access to technologies and expertise that will foster translation of new discoveries into pioneering targeting strategies. Thus, in SAT we develop new therapeutic concepts to improve treatment of common and unmet medical needs.

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Signaling pathways are ensuring the flow/transmission of information, which is essential for life of all organisms. In SAT, we decode physiological signaling pathways, which decode cell-to-cell and environment-to-cell communication to maintain homeostasis and to allow rapid responses to environmental changes. Focus areas cover molecular pathways for immune activation and cell death. All human diseases are associated with deregulations in cellular signal transduction and we determine which exact perturbation are leading pathological signaling.

Dysregulations of signaling pathways, which cause diseases, open new windows of opportunities for pharmacological intervention. By using state of the art technologies such as specific gene editing, genome-wide transcriptomics and proteomic profiling, we decipher such disease-causing vulnerabilities (‘Achilles heels’), which can serve as starting points for clinical translation.

Biomarker Discovery for Diagnostic and Prognostic Purposes

While the past decades have seen tremendous progress in understanding signaling machineries, translation of these findings into clinical innovations is lacking behind. In SAT, we aim to overcome this gap by directly combining basic biomedical research, target identification, target validation and preclinical drug discovery. We use chemical biology and screening and develop small molecule or biologics for precision therapeutic approaches with the aim to improve treatments for cancer and immune diseases. In addition, we define biomarkers that allow prediction and monitoring of therapeutic responses.

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Our Aims

analyze physiological signaling pathways for maintaining health
determine pathological signaling processes leading to diseases
define key targets for therapeutic intervention
discover drug candidates for clinical translation

Krappmann Group

The research aims to unravel cellular signaling pathways controlling immunity and inflammation.

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Core Facility ZWE Assay Development and Screening

Hadian Group

We study the mechanisms of Cell Death Signaling and translate these findings into future drugs using Chemical Biology and Drug Discovery approaches.

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Adding samples inside a biosafety cabinet

Kieser Group

We investigate the molecular basis of cell transformation by the latent membrane protein 1 (LMP1), the primary oncogene of the human Epstein-Barr tumor virus (EBV).

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Schick Group

We are experts in genetic interrogation of medically-relevant cellular death pathways.

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News and Highlights from Our Unit

January 24, 2023

www.frontiersin.org/articles/10.3389/fimmu.2023.1111398/full

Prof. Dr. Daniel Krappmann

Director of the Research Unit Signaling and Translation / Group Leader Signaling and Immunity View profile

Dr. rer. nat. Kamyar Hadian

Deputy Director of the Research Unit Signaling and Translation / Group Leader Cell Signaling and Chemical Biology

Dr. rer. nat. Ina Rothenaigner

Postdoc Hadian Lab

Kristina Herdt

Technical Assistant Krappmann Lab

Christian Pütz

Technical Assistant, IT Administrator Hadian Lab

Franziska Ober

Doctoral Researcher Krappmann Lab

Nicole Wimberger

Doctoral Researcher Krappmann Lab

Prof. Dr. Arnd Kieser

Group Leader Viral Signal Transduction and Therapeutic Intervention Strategies

Vera Kühne

Assistent to the Director

Dr. Andreas Gewies

Postdoc Krappmann Lab

Marie Tofaute

Doctoral Researcher Krappmann Lab

Juliane Tschuck

Doctoral Researcher Hadian Lab

Susanne Pfeiffer

Technical Assistant Schick Lab

Dr. Joel Schick

Group Leader Genetics and Cellular Engineering

Iden Jakob

Secretary

Constanze Sixt

Doctoral Researcher Krappmann Lab

Stefanie Brandner

Technical Assistant Hadian Lab

Srinark Chanikarn

Doctoral Researcher AG Schick

Dr. Kenji Schorpp

Postdoc Hadian Lab

Hao Peng

Doctoral Researcher Schick Lab

Xin Yang

Doctoral Researcher Schick Lab

Dr. rer. nat. Stefanie Weiss

Postdoc Hadian Lab

Dr. Thomas O´Neill

Postdoc Krappmann Lab

Carina Graß

Doctoral Researcher Krappmann Lab

Fabian Giehler

Postdoc Kieser Lab

Helmut Kutz

Technical Assistant, Scientific Officer Kieser Lab

Bahareh Nemati Moud

Postdoc Krappmann Lab

Katrin Demski

Technical Assistant Krappmann Lab

Mr. Roboto

The Mysterious Machine

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2022 Science Advances

Jones, A.N., C. Grass, I. Meininger, A. Geerlof, M. Klostermann, K. Zarnack, D. Krappmann, and M. Sattler

Modulation of pre-mRNA structure by hnRNP proteins regulates alternative splicing of MALT1

2022 Science Signaling

Kutzner, K., S. Woods, O. Karayel, T. Gehring, H. Yin, A. Flatley, C. Grass, N. Wimberger, M.J. Tofaute, T. Seeholzer, R. Feederle, M. Mann, and D. Krappmann

Phosphorylation of serine-893 in CARD11 suppresses the formation and activity of the CARD11-BCL10-MALT1 complex in T and B cells.

2022 Cell Chemical Biology

Napolitano V, Dabrowska A, Schorpp K, Mourão A, Barreto-Duran E, Benedyk M, Botwina P, Brandner S, Bostock M, Chykunova Y, Czarna A, Dubin G, Fröhlich T, Hölscher M, Jedrysik M, Matsuda A, Owczarek K, Pachota M, Plettenburg O, Potempa J, Rothenaigner I, Schlauderer F, Slysz K, Szczepanski A, Mohn K G-I, Blomberg B, Sattler S*, Hadian K*, Popowicz G* and Pyrc K*

Acriflavine, a clinically approved drug, inhibits SARS-CoV-2 and other betacoronaviruses

2022 Cell Death & Differentiation

Xin S, Mueller C, Pfeiffer S, Kraft VAN, Merl-Pham J, Bao X, Feederle R, Jin X, Hauck SM, Schmitt-Kopplin P, Schick JA.

MS4A15 drives ferroptosis resistance through calcium-restricted lipid remodeling.

2021 Science Immunology

O'Neill, T.J., T. Seeholzer, A. Gewies, T. Gehring, F. Giesert, I. Hamp, C. Grass, H. Schmidt, K. Kriegsmann, M.J. Tofaute, K. Demski, T. Poth, M. Rosenbaum, T. Schnalzger, J. Ruland, M. Gottlicher, M. Kriegsmann, R. Naumann, V. Heissmeyer, O. Plettenburg, W. Wurst, and D. Krappmann

TRAF6 prevents fatal inflammation by homeostatic suppression of MALT1 protease.

2020 ACS Central Science

Kraft VAN, Bezjian CT, Pfeiffer S, Ringelstetter L, Müller C, Zandkarimi F, Merl-Pham J, Bao X, Anastasov N, Kössl J, Brandner S, Daniels JD, Schmitt-Kopplin P, Hauck SM, Stockwell B*, Hadian K* and Schick JA*

GTP Cyclohydrolase 1/Tetrahydrobiopterin counteract ferroptosis through lipid remodeling

2020 Nature Communications

Voigt S, Sterz KR, Giehler F, Mohr AW, Wilson JB, Moosmann A, Kieser A.

A central role of IKK2 and TPL2 in JNK activation and viral B-cell transformation.

2020 Molecular Oncology

Yang L, Kraft VAN, Pfeiffer S, Merl-Pham J, Bao X, An Y, Hauck SM, Schick JA.

Nonsense-mediated decay factor SMG7 sensitizes cells to TNFα-induced apoptosis via CYLD tumor suppressor and the noncoding oncogene Pvt1.

2019 Nature Communications

Stangl, A., P.R. Elliott, A. Pinto-Fernandez, S. Bonham, L. Harrison, A. Schaub, K. Kutzner, K. Keusekotten, P.T. Pfluger, F. El Oualid, B.M. Kessler, D. Komander, and D. Krappmann

Regulation of the endosomal SNX27-retromer by OTULIN.

2018 Journal of Biological Chemistry

Brenke JK, Popowicz GM, Schorpp K, Rothenaigner I, Roesner M, Meininger I, Kalinski C, Ringelstetter L, R’kyek O, Jürjens G, Vincendeau M, Plettenburg O, Sattler M, Krappmann D and Hadian K*

Targeting TRAF6 E3 ligase activity with a small molecule inhibitor combats autoimmunity

2018 Nature Communications

Schlauderer, F., T. Seeholzer, A. Desfosses, T. Gehring, M. Strauss, K.P. Hopfner, I. Gutsche, D. Krappmann, and K. Lammens

Molecular architecture and regulation of BCL10-MALT1 filaments.

Latest Publications of Our Research Unit

A proteome-scale map of the SARS-CoV-2-human contactome.

2022 Scientific Article in European Journal of Medicinal Chemistry

Napolitano, V. ; Mroz, P. ; Marciniak, M. ; Kalel, V.C. ; Softley, C. ; Janna Olmos, J.D. ; Tippler, B.G. ; Schorpp, K.K. ; Rioton, S. ; Fröhlich, T. ; Plettenburg, O. ; Hadian, K. ; Erdmann, R. ; Sattler, M. ; Popowicz, G.M. ; Dawidowski, M. ; Dubin, G.

Structure-based design, synthesis and evaluation of a novel family of PEX5-PEX14 interaction inhibitors against Trypanosoma.

2022 Scientific Article in Computational and Structural Biotechnology Journal

Kupczyk, E. ; Schorpp, K.K. ; Hadian, K. ; Lin, S. ; Tziotis, D. ; Schmitt-Kopplin, P. ; Müller, C.

Unleashing high content screening in hit detection - Benchmarking AI workflows including novelty detection.

2022 Scientific Article in Journal of Experimental Medicine

Kessler, N. ; Viehmann, S.F. ; Krollmann, C. ; Mai, K. ; Kirschner, K.M. ; Luksch, H. ; Kotagiri, P. ; Böhner, A.M.C. ; Huugen, D. ; de Oliveira Mann, C.C. ; Otten, S. ; Weiss, S.A. ; Zillinger, T. ; Dobrikova, K. ; Jenne, D. ; Behrendt, R. ; Ablasser, A. ; Bartok, E. ; Hartmann, G. ; Hopfner, K.P. ; Lyons, P.A. ; Boor, P. ; Rosen-Wolff, A. ; Teichmann, L.L. ; Heeringa, P. ; Kurts, C. ; Garbi, N.

Monocyte-derived macrophages aggravate pulmonary vasculitis via cGAS/STING/IFN-mediated nucleic acid sensing.

2022 Scientific Article in Scientific Reports

Napolitano, V. ; Softley, C. ; Blat, A. ; Kalel, V.C. ; Schorpp, K.K. ; Siebenmorgen, T. ; Hadian, K. ; Erdmann, R. ; Sattler, M. ; Popowicz, G.M. ; Dubin, G.