Signaling and Translation SAT

The Research Unit 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.

Director Research Unit SAT

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.

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.

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

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

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

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We collaborate with researchers at the Center as well as national/international cooperation partners and custom-design screening assays for the identification of novel bioactive molecules.

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Prof. Dr. Daniel Krappmann

Director of the Research Unit Signaling and Translation / Group Leader Signaling and Immunity, SAT

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Dr. rer. nat. Kamyar Hadian

Deputy Director of the Research Unit Signaling and Translation / Group Leader Cell Signaling and Chemical Biology / Head Compound Screening Platform

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Dr. Juliane Tschuck

Postdoc Hadian Lab

Prof. Dr. Arnd Kieser

Group Leader Viral Signaling and Targeting Strategies

Dr. Joel Schick

Group Leader Genetics and Cellular Engineering

Dr. rer. nat. Ina Rothenaigner

Postdoc Hadian Lab

Dr. Andreas Gewies

Postdoc Krappmann Lab

Dr. Thomas O´Neill

Postdoc Krappmann Lab

Dr. Fabian Giehler

Postdoc Kieser Lab

Dr. Kenji Schorpp

Postdoc Hadian Lab

Join our Team

team members helping each other. cooperative working concept for success

A new study reveals how two key molecular players – the linear ubiquitin chain assembly complex (LUBAC) and TRAF6 – work together to fine-tune immune signaling in T cells. Published in Nature Communications, the research from the group of Prof.…

Researchers led by Dr. Joel Schick at Helmholtz Munich, in collaboration with Dr. Cathryn Haigh from the National Institutes of Health (NIH), have identified a key mechanism driving brain cell death in prion diseases – a group of rare but fatal…

A better understanding of ferroptosis – an iron-dependent form of cell death – is an essential prerequisite for the treatment of (neuro)degenerative diseases and certain types of cancer. A team of researchers led by Dr. Kamyar Hadian from the…

A team of Helmholtz Munich scientists has made a significant advancement in the understanding of ferroptosis, a complex form of cell death, by successfully detecting it retrospectively in human pathological conditions. This pioneering research,…

Epstein-Barr Virus (EBV) is widespread and very contagious: according to the World Health Association more than 90 percent of the global population are infected with this virus throughout their lives. The virus causes B and T cell lymphomas (cancer…

Understanding ferroptosis is essential for addressing degenerative diseases and certain cancers. Researchers, led by Dr. Kamyar Hadian from Helmholtz Munich, revealed that the Farnesoid X Receptor (FXR), activated by bile acids, serves as a master…

Dr. Kamyar Hadian and Prof. Dr. Ulrike Protzer

Prof. Ulrike Protzer and Dr. Kamyar Hadian and their teams from Helmholtz Munich received the prestigious Bavarian m4 Award, a recognition of their exceptional contributions to the advancement of future medicine and two different groundbreaking…

Burkitt's lymphoma cell, is a cancer of the lymphatic system

A team of researchers from Helmholtz Munich in cooperation with scientists at the University Hospital Münster (UKM) has uncovered a new pathway that promotes the growth of aggressive blood cancer, so-called lymphomas. Survival of many lymphomas…

Daniel Krappmann about his new Research Unit "Signaling and Translation" at Helmholtz Munich

The X-ray of the human brain closeup image

Clinical trials are a milestone in the development of safe and effective drugs and therapies. An antibody developed by Helmholtz Munich is now entering a phase 1 clinical trial. Together with the radiopharmaceutical company ITM Isotope Technologies…

www.helmholtz-munich.de/en/sat

33

Employees

8

Postdocs

9

Doctoral Researchers

6

Technicians

Carina Graß, Franziska Ober, Constanze Sixt, Bahareh Nemati Moud, Irina Antoshkina, Frederick Eberstadt, Alisa Puhach, Göksu Avar, Antonia Keßler, Thomas J. O’Neill, Thomas Seeholzer, Jan Kranich, Thomas Brocker, Katja Lammens, Michael P. Menden, Christina E. Zielinski & Daniel Krappmann

LUBAC modulates CBM complex functions downstream of TRAF6 in T cells

Juliane Tschuck, Vera Skafar, José Pedro Friedmann Angeli, Kamyar Hadian

The metabolic code of ferroptosis: nutritional regulators of cell death

Hao Peng, Susanne Pfeiffer, Borys Varynskyi, Marina Qiu, Chanikarn Srinark, Xiang Jin, Xin Zhang, Katie Williams, Bradley R. Groveman, Simote T. Foliaki, Brent Race, Tina Thomas, Chengxuan Chen, Constanze Müller, Krisztina Kovács, Thomas Arzberger, Stefan Momma, Cathryn L. Haigh & Joel A. Schick

Prion-induced ferroptosis is facilitated by RAC3

Eikan Mishima, Thomas J. O’Neill, Kai P. Hoefig, Deng Chen, Gesine Behrens, Bernhard Henkelmann, Junya Ito, Kiyotaka Nakagawa, Vigo Heissmeyer, Marcus Conrad, and Daniel Krappmann

MALT1 inhibitor MI-2 induces ferroptosis by direct targeting of GPX4

Fabian Giehler, Michael S. Ostertag, Thomas Sommermann, Daniel Weidl, Kai R. Sterz, Helmut Kutz, Andreas Moosmann, Stephan M. Feller, Arie Geerlof, Brigitte Biesinger, Grzegorz M. Popowicz, Johannes Kirchmair & Arnd Kieser

Epstein-Barr virus-driven B cell lymphoma mediated by a direct LMP1-TRAF6 complex

Anand Ramani, Giovanni Pasquini, Niklas J. Gerkau, Vaibhav Jadhav, Omkar Suhas Vinchure, Nazlican Altinisik, Hannes Windoffer, Sarah Muller, Ina Rothenaigner, Sean Lin, Aruljothi Mariappan, Dhanasekaran Rathinam, Ali Mirsaidi, Olivier Goureau, Lucia Ricci-Vitiani, Quintino Giorgio D’Alessandris, Bernd Wollnik, Alysson Muotri, Limor Freifeld, Nathalie Jurisch-Yaksi, Roberto Pallini, Christine R. Rose, Volker Busskamp, Elke Gabriel, Kamyar Hadian & Jay Gopalakrishnan

Reliability of high-quantity human brain organoids for modeling microcephaly, glioma invasion and drug screening

Tschuck, J. ; Tonnus, W. ; Gavali, S. ; Kolak, A. ; Mallais, M. ; Maremonti, F. ; Sato, M. ; Rothenaigner, I. ; Friedmann Angeli, J.P. ; Pratt, D.A. ; Linkermann, A. ; Hadian, K.

Seratrodast inhibits ferroptosis by suppressing lipid peroxidation.

Tschuck, J. ; Padmanabhan Nair, V. ; Galhoz, A. ; Zaratiegui, C. ; Tai, H.-M. ; Ciceri, G. ; Rothenaigner, I. ; Tchieu, J. ; Stockwell, B.R. ; Studer, L. ; Cabianca, D.S. ; Menden, M.P. ; Vincendeau, M. ; Hadian, K.

Suppression of ferroptosis by vitamin A or radical-trapping antioxidants is essential for neuronal development.

Hao Peng, Shan Xin, Susanne Pfeiffer, Constanze Müller, Juliane Merl-Pham, Stefanie M. Hauck, Patrick N. Harter, Daniel Spitzer, Kavi Devraj, Borys Varynskyi, Thomas Arzberger, Stefan Momma & Joel A. Schick

Fatty acid-binding protein 5 is a functional biomarker and indicator of ferroptosis in cerebral hypoxia

Juliane Tschuck, Lea Theilacker, Ina Rothenaigner, Stefanie A. I. Weiß, Banu Akdogan, Van Thanh Lam, Constanze Müller, Roman Graf, Stefanie Brandner, Christian Pütz, Tamara Rieder, Philippe Schmitt-Kopplin, Michelle Vincendeau, Hans Zischka, Kenji Schorpp, Kamyar Hadian

Farnesoid X receptor activation by bile acids suppresses lipid peroxidation and ferroptosis

Nicole Wimberger, Franziska Ober, Göksu Avar, Michael Grau, Wendan Xu, Georg Lenz, Michael P. Menden, Daniel Krappmann

Oncogene-induced MALT1 protease activity drives post-transcriptional gene expression in malignant lymphomas

Kamyar Hadian, Brent R. Stockwell

The therapeutic potential of targeting regulated non-apoptotic cell death

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

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

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.