piwik-script

Deutsch Intern
Rudolf Virchow Center for Experimental Biomedicine

Lorenz Group

About the Lorenz Group

Cells have evolved a staggering range of mechanisms to regulate the abundance, localization, conformation, and activity of proteins in response to biological stimuli. These mechanisms are typically driven by posttranslational protein modifications. Sonja Lorenz’ lab aims to unravel the structural basis and functional consequences of posttranslational modifications with a particular focus on the ubiquitin system in tumorigenesis and infection. To this end the lab combines high-resolution structural techniques (cryo-electron microscopy, X-ray crystallography, NMR spectroscopy) with biophysical, biochemical, and cell biological techniques.

Understanding and targeting ubiquitination and phosphorylation networks

The ubiquitin system regulates countless physiological and disease-associated processes and has emerged as a powerful arena for therapeutic efforts. Ubiquitination is mediated by a cascade of ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2) and ubiquitin ligases (E3), counteracted by deubiquitinases. E3s have pivotal roles in determining the specificity of ubiquitin signaling by recruiting specific substrates for modification and defining which types of ubiquitin modifications they are decorated with, thus triggering particular signaling responses. With an estimated 1000 members in the human proteome, the E3 family is the most diversified among the different classes of ubiquitination enzymes and provides particularly interesting targets for therapeutic interference.The immense potential of modulating the activities of E3 enzymes for therapeutic benefit has become evident from the finding that the clinical efficacy of thalidomide in the treatment of hematological malignancies originates from its interaction with a particular RING-type E3, CRL4CRBN. This milestone discovery has given rise to several immunomodulatory drugs and refueled the development of proteolysis-targeting chimeras (PROTACs) that harness the activities of RING-type E3 enzymes to mark pathogenic proteins for degradation. In contrast, the development of small-molecule probes targeting HECT-type E3 enzymes is still in its infancy  – despite the presence of a potentially ‘druggable’ active site in these ligases and their clear pathophysiological significance. 

The Lorenz lab investigates the macromolecular complexes, conformational dynamics, and functions of  HECT-type ubiquitin ligases to understand the mechanisms underlying their substrate specificity, linkage specificity, regulation, and vulnerability to small-molecule inhibitors. A major focus is on ligases crucial in tumorigenesis, e.g. HUWE1. A second line of research elucidates the crosstalk of ubiquitination and phosphorylation in infectious disease. Work in the Lorenz lab is supported by the DFG Emmy Noether Program, GRK 2243 (“Understanding ubiquitylation: from molecular mechanism to disease”), FOR 2314 (“Targeting therapeutic windows in essential cellular processes for tumor therapy”), and the Mildred Scheel Cancer Center (Deutsche Krebshilfe). In 2018 Sonja Lorenz was named an EMBO Young Investigator.

Lab Page

Liess A, Kucerova A, Schweimer K, Yu L, Roumeliotis T, Diebold M, Dybkov O, Sotriffer C, Urlaub H, Choudhary J, Mansfeld J, Lorenz S (2019). Auto-inhibition mechanism of the ubiquitin-conjugating enzyme UBE2S by auto-ubiquitination. Structure 27(8):1195-1210

featured in Bodrug T, Brown NG (2019). UBE2S learns self control. Structure 27(8):11185-1187 


Deol KK, Lorenz S*, Strieter ER (2019). Enzymatic Logic of Ubiquitin Chain Assembly. Front Physiol. 10:835


Ries LK, Sander B, Deol KK, Letzelter MA, Strieter ER, Lorenz S (2019). Analysis of ubiquitin recognition by the HECT ligase E6AP provides insight into its linkage specificity. J Biol Chem 294: 6113-6129


Chen D, Gehringer M, Lorenz S (2018) Developing small-molecule inhibitors of HECT-type ubiquitin ligases for therapeutic applications: challenges and opportunities. ChemBioChem 19(20):2123-2135


Lorenz S (2017). Structural mechanisms of HECT-type ubiquitin ligases. Biol Chem 399(2):127-145


Sander B, Xu W, Eilers M, Popov N, Lorenz S (2017). A conformational switch regulates the ubiquitin ligase HUWE1. eLife 6:e21036


Lorenz S, Bhattacharyya M, Feiler C, Rape M, Kuriyan J (2016). Crystal structure of a Ube2S-ubiquitin conjugate. PLoS One 11(2):e0147550


Lorenz S, Deng T, Hantschel O, Superti-Furga G, Kuriyan J (2015). Crystal structure of an SH2-kinase construct of c-Abl and effect of the SH2 domain on kinase activity. Biochemical Journal, 468(2):283-91


Lorenz S, Cantor AJ, Rape M, Kuriyan J (2013). Macromolecular juggling by ubiquitylation enzymes. BMC Biology 11: 65


Wickliffe KE, Lorenz S*, Wemmer DE, Kuriyan J, Rape M (2011). The mechanism of linkage-specific ubiquitin chain elongation by a single subunit E2. Cell 144(5): 769-781

*shared first and shared corresponding author

Dr. Johanna Bialas

Postdoc
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: Haus D15
Room: 00.031

Maria Gallant

Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: Haus D15
Room: 00.031

Julia Haubenreißer

Technische/r Assistent/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: Haus D15

Anna Liess

Doktorand/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: Haus D15
Room: 00.031

Dr. Yahui Liu

Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: Haus D15

Dr. Bing Liu

Postdoc
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: Haus D15
Room: 00.031

Dr. Sonja Lorenz

Gruppenleiterin
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: Haus D15
Room: 00.030

Rahul Nair

Doktorand/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: Haus D15

Barbara Orth

Doktorand/in
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: Haus D15

Ayshwarya Seenivasan

Doktorandin
Rudolf-Virchow-Zentrum für Experimentelle Biomedizin
Universität Würzburg
Josef-Schneider-Str. 2
97080 Würzburg
Deutschland
Building: Haus D15

Current position

since 2014       Independent group leader (Emmy Noether Program) at the Rudolf Virchow Center, University of Würzburg

Research Experience

2008-2014       Postdoctoral fellow with Prof. John Kuriyan, University of California, Berkeley/Howard Hughes Medical Institute, USA

Education

2004-2008       DPhil, Biochemistry and Molecular Biophysics, University of Oxford, UK (Prof. Iain Campbell & Prof. Martin Noble)

Fellowships and Awards

  • EMBO Young Investigator Program                                                                            
  • DFG (German Research Foundation) Emmy Noether Program                                    
  • Leukemia and Lymphoma Society (USA), career development program                     
  • Medical Schools Council (UK), travel grant                                                                 
  • German National Academic Foundation (Studienstiftung des deutschen Volkes)

Academic Commitments

  • Founding member, ‘Mildred Scheel-Nachwuchszentrumr‘, Deutsche Krebshilfe (2019-2024)
  • Co-spokesperson, RTG (Research Training Group) 2243, ‘Understanding ubiquitylation: from molecular mechanism to disease’, DFG (2017-2021)
  • Member of faculty search committees, Würzburg (since 2017)
  • Selection panel member,  German National Academic Foundation (Studienstiftung des deutschen Volkes) (since 2016)
  • Mentor, ‘Mentoring Life Sciences’-program, Graduate School of Life Sciences, Würzburg (since 2014)
  • Spokesperson, UK-doctoral student delegation at the Lindau Meeting of Nobel Laureates (2007)                  
  • President, Oxford University Biochemical Society, Oxford, UK(2006-2007)

More information on her LinkedIn profile

Position
Member - Graduate School of Life Sciences (GSLS)
Member - various GSLS thesis committees (biomedicine as well as infection & immunity)
Supervisor - Graduate School of Life Sciences, Biomedicine

The current term program can be found here.