Prof Stefan Knapp studied Chemistry at the University of Marburg (Germany) and at the University of Illinois (USA). He did his PhD in protein crystallography at the Karolinska Institute in Stockholm (Sweden) (1996) and continued his career at the Karolinska Institute as a postdoctoral scientist (1996-1999). In 1999, he joined the Pharmacia Corporation as a principal research scientist in structural biology and biophysics. He left the company in 2004 to set up a research group at the Structural Genomics Consortium at Oxford University (SGC). From 2008 to 2015 he was a Professor of Structural Biology at the Nuffield Department of Clinical Medicine (NDM) at Oxford University (UK) and between 2012 and 2015 he was the Director for Chemical Biology at the Target Discovery Institute (TDI). He joined Frankfurt University (Germany) in 2015 as a Professor of Pharmaceutical Chemistry and the Buchmann Institute of Molecular Life Sciences. He remains associated to the SGC as a visiting Professor at Oxford and he is also adjunct Professor of the George Washington University. Since 2017 he is the CSO of the newly founded SGC node at the Goethe-University Frankfurt. His research interests are the rational design of selective inhibitors that target protein kinases as well as protein interactions modules that function as reader domains of the epigenetic code.
My laboratory is interested in understanding molecular mechanisms that regulate protein function of key signalling molecules and how these mechanisms can be utilized for the development of highly selective and potent inhibitors (chemical probes). As a basis for this work we have generated a comprehensive set of high resolution crystal structures that cover most members of the protein family of interest. We are particularly interested in protein interactions module of the bromodomain family that specifically recognize ε-N-lysine acetylation motifs, a key event in the reading process of epigenetic marks. This effort generated several highly selective chemical probes targeting bromodomains. A second research focus is on protein kinases. Our laboratory has solved a comprehensive set of crystal structure of this large protein family offering the opportunity to understand molecular mechanisms of their regulation and developing new strategies for their selective targeting. We developed for example a number of highly selective inhibitors by exploring unusual binding modes and allosteric binding sites. A particular focus of the laboratory is also to understand structural mechanisms leading to slow binding kinetics as part of the K4DD consortium.
Mandel S, Hanke T, Mathea S, Chatterjee D, Saraswati H, Berger BT, Schwalm MP, Yamamoto S, Tawada M, Takagi T, Ahmed M, Röhm S, Corrionero A, Alfonso P, Baena M, Elson L, Menge A, Krämer A, Pereira R, Müller S, Krause DS, Knapp S
ACS Chem Biol. 2025-4-14 . .doi: 10.1021/acschembio.5c00097
PMID: 40227881Miletić N, Weckesser J, Mosler T, Rathore R, Hoffmann ME, Gehrtz P, Schlesiger S, Hartung IV, Berner N, Wilhelm S, Müller J, Adhikari B, Němec V, Sivashanmugam SA, Elson L, Holzmann H, Schwalm MP, Hoffmann L, Abdul Azeez KR, Müller S, Kuster B, Wolf E, Đikić I, Knapp S
ACS Chem Biol. 2025-2-11 . .doi: 10.1021/acschembio.4c00812
PMID: 39932098Deutscher RCE, Meyners C, Repity ML, Sugiarto WO, Kolos JM, Maciel EVS, Heymann T, Geiger TM, Knapp S, Lermyte F, Hausch F
Chem Sci. 2025-2-7 . .doi: 10.1039/d4sc06917j
PMID: 39916884Wang X, Sun J, Ahmad S, Yang D, Li F, Chan UH, Zeng H, Simoben CV, Houliston S, Dong A, Bolotokova A, Gibson E, Kutera M, Ghiabi P, Kondratov I, Matviyuk T, Chuprina A, Mavridi D, Lenz C, Joerger AC, Brown BD, Heath RB, Yue WW, Robbie LK, Beyett TS, Müller S, Knapp S, Harding R, Schapira M, Brown PJ, Santhakumar V, Ackloo S, Arrowsmith CH, Edwards AM, Peng H, Halabelian L
bioRxiv. 2025-2-3 . .doi: 10.1101/2025.01.17.633682
PMID: 39896675Schwalm MP, Knapp S
SLAS Discov. 2025-1-20 . 100214 .doi: 10.1016/j.slasd.2025.100214
PMID: 39826872Münick P, Strubel A, Balourdas DI, Funk JS, Mernberger M, Osterburg C, Dreier B, Schaefer JV, Tuppi M, Yüksel B, Schäfer B, Knapp S, Plückthun A, Stiewe T, Joerger AC, Dötsch V
Nat Struct Mol Biol. 2025-1-10 . .doi: 10.1038/s41594-024-01456-7
PMID: 39789211Lotz R, Osterburg C, Chaikuad A, Weber S, Akutsu M, Machel AC, Beyer U, Gebel J, Löhr F, Knapp S, Dobbelstein M, Lu X, Dötsch V
Cell Death Dis. 2025-1-7 . 16(1):4 .doi: 10.1038/s41419-024-07320-2
PMID: 39762243Virtanen A, Kettunen V, Musta K, Räkköläinen V, Knapp S, Haikarainen T, Silvennoinen O
Adv Biol Regul. 2025-1-5 . 101072 .doi: 10.1016/j.jbior.2024.101072
PMID: 39755448Schwalm MP, Menge A, Elson L, Greco FA, Robers MB, Müller S, Knapp S
ACS Chem Biol. 2025-1-4 . .doi: 10.1021/acschembio.4c00450
PMID: 39753207Haag A, Němec V, Janovská P, Bartošíková J, Adhikari B, Müller J, Schwalm MP, Čada Š, Ohmayer U, Daub H, Kim Y, Born F, Wolf E, Bryja V, Knapp S
J Med Chem. 2024-12-27 . .doi: 10.1021/acs.jmedchem.4c02201
PMID: 39729064