Lorenz, Sonja, Dr.

Independent Group Leader

2003 Diploma in Biochemistry, University of Regensburg, Germany
2004 - 2008 Ph.D. Student, Laboratories of Iain D. Campbell & Martin Noble, University of Oxford, United Kingdom
2009 - 2013 Leukemia & Lymphoma Society, Career Development Fellow, Laboratory of John Kuriyan, University of California, Berkeley, CA, USA
2013-2014 Howard Hughes Medical Institute, Research Associate, Laboratory of John Kuriyan, University of California, Berkeley, CA, USA
2014-2020 Emmy Noether Group Leader, Rudolf Virchow Center for Experimental Biomedicine, University of Wuerzburg, Germany
Since 2021 Independent Group Leader, MPI for Multidisciplinary Sciences, Goettingen, Germany

Major Research Interests

1. Specificity and regulation of ubiquitin ligases
2. Function of ubiquitin ligases in neurodevelopmental and infectious diseases
3. Therapeutic exploitation of ubiquitin ligases

Ubiquitination is a central posttranslational modification that dynamically decorates ~50.000 cellular protein sites with ubiquitin signals, thereby regulating myriad aspects of eukaryotic physiology. In additional, ubiquitin has recently been found conjugated to non-protein biomolecules, further expanding the signaling capacity of ubiquitination. The ubiquitin system is thus of immense interest to fundamental research and has emerged as a major arena for drug discovery. Our lab aims to establish paradigms of specificity in ubiquitination, focusing on the class of HECT-type ubiquitin ligases. We combine a wide spectrum of structural biology techniques – cryo-electron microscopy, X-ray crystallography, and NMR – with chemical biology, biophysical and cell-based imaging approaches. We utilize mechanistic insights for the development of small-molecule probes to interrogate ubiquitination activities in cells, providing entry points for therapeutic applications.

Homepage Department/Research Group

https://www.mpinat.mpg.de/de/lorenz

Selected Recent Publications

Orth B*, Pohl P*, Aust F, Ji Y, Seenivasan A, Dybkov O, Liang XJ, Bock L, Leidner F, Levantovsky S, Schardey P, Sander P, Disch NJ, Trautz ML, Mizi A, Papantonis A, Lenz C, Grubmüller H, Steinchen W, Behrends C, Urlaub H, Gehringer M, and Lorenz S#: Selective ubiquitination of drug-like small molecules by the ubiquitin ligase HUWE1. Nature Communications, 16: 8182 (2025).

Fokkens TJ*, Rauh ET*, Wolter M, Sebald H, Mitnacht M, Ainatzi S, Sprick S, Teschke L, Eisenhuth N, Huibregtse JM, Butter F, Urlaub H, Karnkowska A, Schleicher U, Steinchen W, Janzen CJ, Lorenz S#: A Leishmania virulence factor harnesses an allosteric kinase switch to regulate its ubiquitin ligase activity. Molecular Cell, 85: 3711–3728.e11 (2025).

Düring J*, Wolter M*, Toplak JJ, Torres C, Dybkov O, Fokkens TJ, Bohnsack KE, Urlaub H, Steinchen W, Dienemann C, Lorenz S#: Structural mechanisms of autoinhibition and substrate recognition by the ubiquitin ligase HACE1. Nature Structural and Molecular Biology, 31: 364 (2024).

Ambrozkiewcz MC# & Lorenz S#: Understanding ubiquitination in neurodevelopment by integrating insights across space and time. Nature Structural and Molecular Biology, 32: 14 (2025).

Nair R, Seenivasan A, Liu B, Chen D, Lowe E, Lorenz S#: Reconstitution and structural analysis of a HECT ligase-ubiquitin complex via an activity-based probe. ACS Chemical Biology, 16: 1615 (2021).

Liess A*, Kucerova A*, Schweimer K, Urlaub H, Mansfeld J#, Lorenz S#: Dimerization regulates the human APC/C-associated ubiquitin-conjugating enzyme UBE2S. Science Signaling 13: eaba8208 (2020).

Liess A*, Kucerova A*, Schweimer K, Yu L, Roumeliotis T, Diebold M, Dybkov O, Sotriffer C, Urlaub H, Choudhary J, Mansfeld J#, Lorenz S#: Autoinhibition mechanism of the ubiquitin-conjugating enzyme UBE2S by autoubiquitination. Structure, 27: 1195.e7 (2019).