Biography

As a cryo-EM staff scientist, I operate advanced cryo-electron microscopes and support researchers in preparing samples, optimizing imaging conditions, and collecting and analyzing structural data on biomedical targets that may ultimately contribute to the development of novel therapeutics. I am especially passionate about training researchers in all aspects of cryo-EM, with the goal of enabling them to work independently. My background is in protein biochemistry and X-ray crystallography, where I worked in multidisciplinary drug-discovery teams alongside synthetic organic and computational chemists on the development of anticancer therapeutics, determining and depositing more than 60 crystal structures of protein–inhibitor complexes in the Protein Data Bank (PDB). My work later expanded to the study of membrane receptors using cryo-EM, allowing me to determine their full-length structures, uncover mechanisms of disease-related signaling, and identify a potential therapeutic target for cancer. Looking ahead, I am excited to explore electron tomography and in situ cryo-EM to study disease-related proteins in their native cellular environment.

Publications

Cryo-EM analyses of KIT and oncogenic mutants reveal structural oncogenic plasticity and a target for therapeutic intervention

Stefan G. Krimmer, Nicole Bertoletti, Yoshihisa Suzuki, Luka Katic, Jyotidarsini Mohanty, Sheng Shu, Sangwon Lee, Irit Lax, Wei Mi, Joseph Schlessinger

Proceedings of the National Academy of Sciences, Vol. 120, Issue 13

2023 March

Unveiling molecular insights into the mechanism of activation of oncogenic phosphoinositide 3-kinase mutants

Stefan G. Krimmer, Joseph Schlessinger

Proceedings of the National Academy of Sciences, Vol. 119, Issue 50

2022 December

Insights on JAK2 Modulation by Potent, Selective, and Cell-Permeable Pseudokinase-Domain Ligands

Maria-Elena Liosi, Joseph A. Ippolito, Sean P. Henry, Stefan G. Krimmer, Ana S. Newton, Kara J. Cutrona, Rene A. Olivarez, Jyotidarsini Mohanty, Joseph Schlessinger, William L. Jorgensen

Journal of Medicinal Chemistry, Vol. 65, Issue 12, Pages 8380-8400

2022 January

Conversion of a False Virtual Screen Hit into Selective JAK2 JH2 Domain Binders Using Convergent Design Strategies

Sean P. Henry, Maria-Elena Liosi, Joseph A. Ippolito, Kara J. Cutrona, Stefan G. Krimmer, Ana S. Newton, Joseph Schlessinger, William L. Jorgensen

ACS Medicinal Chemistry Letters, Vol. 13, Issue 5, Pages 819-826

2022 January

Structural basis for ligand reception by anaplastic lymphoma kinase

Tongqing Li, Steven E. Stayrook, Yuko Tsutsui, Jianan Zhang, Yueyue Wang, Hengyi Li, Andrew Proffitt, Stefan G. Krimmer, Mansoor Ahmed, Olivia Belliveau, Ian X. Walker, Krishna C. Mudumbi, Yoshihisa Suzuki, Irit Lax, Diego Alvarado, Mark A. Lemmon, Joseph Schlessinger, Daryl E. Klein

Nature, Vol. 600, Issue 7887, Pages 148-152

2021 January

Indoloxytriazines as binding molecules for the JAK2 JH2 pseudokinase domain and its V617F variant

Ana S. Newton, Maria-Elena Liosi, Sean P. Henry, Luca Deiana, John C. Faver, Stefan G. Krimmer, David E. Puleo, Joseph Schlessinger, William L. Jorgensen

Tetrahedron Letters, Vol. 77, Pages 153248

2021 January

Metadynamics as a postprocessing method for virtual screening with application to the pseudokinase domain of JAK2

Kara J. Cutrona, Ana S. Newton, Stefan G. Krimmer, Julian Tirado-Rives, William L. Jorgensen

Journal of Chemical Information and Modeling, Vol. 60, Issue 9, Pages 4403-4415

2020 January

Selective Janus Kinase 2 (JAK2) Pseudokinase Ligands with a Diaminotriazole Core

Maria-Elena Liosi, Stefan G. Krimmer, Ana S. Newton, Thomas K. Dawson, David E. Puleo, Kara J. Cutrona, Yoshihisa Suzuki, Joseph Schlessinger, William L. Jorgensen

Journal of Medicinal Chemistry, Vol. 63, Issue 10, Pages 5324-5340

2020 January

Bayesian analysis of isothermal titration calorimetry for binding thermodynamics

Trung Hai Nguyen, Ariën S. Rustenburg, Stefan G. Krimmer, Hexi Zhang, John D. Clark, Paul A. Novick, Kim Branson, Vijay S. Pande, John D. Chodera, David D. L. Minh

PLoS ONE, Vol. 13, Issue 9, Pages e0203224

2018 January

Optimization of Pyrazoles as Phenol Surrogates to Yield Potent Inhibitors of Macrophage Migration Inhibitory Factor

Vinay Trivedi‐Parmar, Michael J. Robertson, José A. Cisneros, Stefan G. Krimmer, William L. Jorgensen

ChemMedChem, Vol. 13, Issue 11, Pages 1092-1097

2018 January

Elucidating the origin of long residence time binding for inhibitors of the metalloprotease thermolysin

Jonathan Cramer, Stefan G. Krimmer, Veronica Fridh, Tobias Wulsdorf, Robert Karlsson, Andreas Heine, Gerhard Klebe

ACS Chemical Biology, Vol. 12, Issue 1, Pages 225-233

2017 January

How Nothing Boosts Affinity: Hydrophobic Ligand Binding to the Virtually Vacated S<sub>1</sub>′ Pocket of Thermolysin

Stefan G. Krimmer, Jonathan Cramer, Johannes Schiebel, Andreas Heine, Gerhard Klebe

Journal of the American Chemical Society, Vol. 139, Issue 30, Pages 10419-10431

2017 January

Paying the Price of Desolvation in Solvent-Exposed Protein Pockets: Impact of Distal Solubilizing Groups on Affinity and Binding Thermodynamics in a Series of Thermolysin Inhibitors

Jonathan Cramer, Stefan G. Krimmer, Andreas Heine, Gerhard Klebe

Journal of Medicinal Chemistry, Vol. 60, Issue 13, Pages 5791-5799

2017 January

Adding a Hydrogen Bond May Not Help: Naphthyridinone vs Quinoline Inhibitors of Macrophage Migration Inhibitory Factor

Thomas K. Dawson, Pawel Dziedzic, Michael J. Robertson, José A. Cisneros, Stefan G. Krimmer, Ana S. Newton, Julian Tirado-Rives, William L. Jorgensen

ACS Medicinal Chemistry Letters, Vol. 8, Issue 12, Pages 1287-1291

2017 January

Active Site Mapping of an Aspartic Protease by Multiple Fragment Crystal Structures: Versatile Warheads to Address a Catalytic Dyad

Nedyalka Radeva, Johannes Schiebel, Xiaojie Wang, Stefan G. Krimmer, Kan Fu, Martin Stieler, Frederik R. Ehrmann, Alexander Metz, Thomas Rickmeyer, Michael Betz, Johan Winquist, Ah Young Park, Franziska U. Huschmann, Manfred S. Weiss, Uwe Mueller, Andreas Heine, Gerhard Klebe

Journal of Medicinal Chemistry, Vol. 59, Issue 21, Pages 9743-9759

2016 January

High-Throughput Crystallography: Reliable and Efficient Identification of Fragment Hits

Johannes Schiebel, Stefan G. Krimmer, Karine Röwer, Anna Knörlein, Xiaojie Wang, Ah Young Park, Martin Stieler, Frederik R. Ehrmann, Kan Fu, Nedyalka Radeva, Michael Krug, Franziska U. Huschmann, Steffen Glöckner, Manfred S. Weiss, Uwe Mueller, Gerhard Klebe, Andreas Heine

Structure, Vol. 24, Issue 8, Pages 1398-1409

2016 January

Six Biophysical Screening Methods Miss a Large Proportion of Crystallographically Discovered Fragment Hits: A Case Study

Johannes Schiebel, Nedyalka Radeva, Stefan G. Krimmer, Xiaojie Wang, Martin Stieler, Frederik R. Ehrmann, Kan Fu, Alexander Metz, Franziska U. Huschmann, Manfred S. Weiss, Uwe Mueller, Andreas Heine, Gerhard Klebe

ACS Chemical Biology, Vol. 11, Issue 6, Pages 1693-1701

2016 January

Impact of Surface Water Layers on Protein-Ligand Binding: How Well Are Experimental Data Reproduced by Molecular Dynamics Simulations in a Thermolysin Test Case?

Michael Betz, Tobias Wulsdorf, Stefan G. Krimmer, Gerhard Klebe

Journal of Chemical Information and Modeling, Vol. 56, Issue 1, Pages 223-233

2016 January

Stefan Krimmer

Biography

Publications