Welcome to the Sarott Laboratory

Research

  • Chemically Induced Proximity

    From cell signaling at the membrane to the nucleus, bringing proteins closely together is often sufficient to activate function. We develop small molecules that induce new protein-protein interactions to reprogram cellular signaling and unlock novel therapeutic strategies.

  • Activating Cancer Cell Death

    Most small molecule cancer therapies center on silencing cancer-driving proteins, but they fail to effectively destroy tumors. We take inspiration from the success of immunotherapy and develop molecules that directly, potently, and specifically activate cancer cell death.

  • Reprogramming Gene Expression

    Deregulated gene expression is at the heart of tumor formation. However, transcription factors, the effectors of gene regulation, have long eluded drug discovery. We develop molecules that use the principle of induced proximity to engender oncogenic transcription factors with neomorphic activities and induce therapetic gene programs.

Meet the Team

  • Roman C. Sarott

    Principal Investigator

    Ph.D. ETH Zürich

  • Oliver J. Stratton

    Postdoc

    Ph.D. Universtiy of Oxford

  • Julius A. Guenther

    Ph.D. Student

    M.Sc. Heidelberg University

  • Raphaela Küppers

    Ph.D. Student, co-advised with Prof. F. Thomas (Heidelberg University)

    M.Sc. Heidelberg University

  • Ryan P. Golden

    Visiting Ph.D. Student (Stanford University)

    B.S. UC Berkeley

  • Nathan Kloszewski

    Master’s Student

    Matter to Life

  • Jeyanthram Venkatesan

    Administrative Assistant

Publications

2025

M. Ashley, C. Borsari, S. Cazzamalli, J. Chu, Y. Lee, P. Perlíková, R. C. Sarott, B. J. Simmons, X. Xu, N. A. Patil, C. Kounde, S. Wang, Announcing the Early Career Board of Journal of Medicinal Chemistry. Journal of Medicinal Chemistry 68, 13131-13136 (2025), https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c01588

S. J. Garza, B. Kicin, R. C. Sarott, P. Pfaff, M. Kosar, T. Weishaar, P. Schnacke, B. T. Lobingier, E. M. Carreira, J. A. Frank, Real-Time Optical Control of CB1 Receptor Signaling In Vitro with Tethered Photoswitchable (−)-trans-Δ9-Tetrahydrocannabinol Derivatives. Journal of the American Chemical Society 147, 23482-23491 (2025), https://pubs.acs.org/doi/full/10.1021/jacs.3c06622.

M. Kosar, T. Perera, R. L. Z. Ganzoni, R. C. Sarott, L. Borrega-Roman, R. M. Vitale, A. Ligresti, A. C. Rufer, W. Guba, U. Grether, E. M. Carreira, D. B. Veprintsev, D. A. Sykes, Profiling Allosteric Modulators of CB1R with an Allosteric Fluoroprobe. Angewandte Chemie International Edition 64, e202421885 (2025), https://onlinelibrary.wiley.com/doi/10.1002/anie.202421885.

M. N. Nix, S. Gourisankar, R. C. Sarott, B. G. Dwyer, S. A. Nettles, M. M. Martinez, H. Abuzaid, H. Yang, Y. Wang, J. M. Simanauskaite, B. A. Romero, H. M. Jones, A. Krokhotin, T. N. Lowensohn, L. Chen, C. Low, M. M. Davis, D. Fernandez, T. Zhang, M. R. Green, S. M. Hinshaw, N. S. Gray, G. R. Crabtree, A Bivalent Molecular Glue Linking Lysine Acetyltransferases to Oncogene-induced Cell Death. bioRxiv preprint (2025), https://www.biorxiv.org/content/10.1101/2025.03.14.643404v1.

Q. Geng, Z. Jiang, W. S. Byun, K. A. Donovan, Z. Zhuang, F. Jiang, H. M. Jones, H. Razumkov, M. T. Tang, R. C. Sarott, E. S. Fischer, S. M. Corsello, S. M. Hinshaw, N. S. Gray, Development of Potent and Selective CK1α Molecular Glue Degraders. Journal of Medicinal Chemistry 68, 3180-3196 (2025), https://pubs.acs.org/doi/10.1021/acs.jmedchem.4c02415.

L. Borrega-Roman, B. L. Hoare, M. Kosar, R. C. Sarott, K. J. Patej, J. Bouma, M. Scott-Dennis, E. J. Koers, T. Gazzi, L. Mach, S. Barrondo, J. Sallés, W. Guba, E. Kusznir, M. Nazaré, A. C. Rufer, U. Grether, L. H. Heitman, E. M. Carreira, D. A. Sykes, D. B. Veprintsev, A universal cannabinoid CB1 and CB2 receptor TR-FRET kinetic ligand-binding assay. Frontiers in Pharmacology 16 (2025), https://doi.org/10.3389/fphar.2025.1469986.

M. Kosar, R. C. Sarott, D. A. Sykes, A. E. G. Viray, R. M. Vitale, N. Tomašević, X. Li, R. L. Z. Ganzoni, B. Kicin, L. Reichert, K. J. Patej, U. Gómez-Bouzó, W. Guba, P. J. McCormick, T. Hua, C. W. Gruber, D. B. Veprintsev, J. A. Frank, U. Grether, E. M. Carreira, Flipping the GPCR Switch: Structure-Based Development of Selective Cannabinoid Receptor 2 Inverse Agonists. ACS Central Science 10, 956-968 (2024), https://pubs.acs.org/doi/10.1021/acscentsci.3c01461.

2024

X. Zhu, W. S. Byun, D. E. Pieńkowska, K. T. Nguyen, J. Gerhartz, Q. Geng, T. Qiu, J. Zhong, Z. Jiang, M. Wang, R. C. Sarott, S. M. Hinshaw, T. Zhang, L. D. Attardi, R. P. Nowak, N. S. Gray, Activating p53<sup>Y220C</sup> with a Mutant-Specific Small Molecule. bioRxiv preprint (2024), https://www.biorxiv.org content/10.1101/2024.10.23.619961v1.

R. C. Sarott, S. Gourisankar, B. Karim, S. Nettles, H. Yang, B. G. Dwyer, J. M. Simanauskaite, J. Tse, H. Abuzaid, A. Krokhotin, T. Zhang, S. M. Hinshaw, M. R. Green, G. R. Crabtree, N. S. Gray, Relocalizing transcriptional kinases to activate apoptosis. Science 386, eadl5361 (2024), https://www.science.org/doi/10.1126/science.adl5361.

2023

R. C. Sarott, I. You, Y.-D. Li, S. T. Toenjes, K. A. Donovan, P. Seo, M. Ordonez, W. S. Byun, M. M. Hassan, F. Wachter, E. T. Chouchani, M. Słabicki, E. S. Fischer, B. L. Ebert, S. M. Hinshaw, N. S. Gray, Chemical Specification of E3 Ubiquitin Ligase Engagement by Cysteine-Reactive Chemistry. Journal of the American Chemical Society 145, 21937-21944 (2023), https://pubs.acs.org/doi/full/10.1021/jacs.3c06622.

M. Freis, M. Balkenhohl, D. M. Fischer, T. Georgiev, R. C. Sarott, E. M. Carreira, Cobalt-Catalyzed Aerobic Aminocyclization of Unsaturated Amides for the Synthesis of Functionalized γ- and δ-Lactams. Organic Letters 25, 6380-6384 (2023), https://pubs.acs.org/doi/10.1021/acs.orglett.3c02390.

M. Kosar, D. A. Sykes, A. E. G. Viray, R. M. Vitale, R. C. Sarott, R. L. Ganzoni, D. Onion, J. M. Tobias, P. Leippe, C. Ullmer, E. A. Zirwes, W. Guba, U. Grether, J. A. Frank, D. B. Veprintsev, E. M. Carreira, Platform Reagents Enable Synthesis of Ligand-Directed Covalent Probes: Study of Cannabinoid Receptor 2 in Live Cells. Journal of the American Chemical Society 145, 15094-15108 (2023), https://pubs.acs.org/doi/10.1021/jacs.2c13629.

2022

T. Gazzi, B. Brennecke, K. Atz, C. Korn, D. Sykes, G. Forn-Cuni, P. Pfaff, R. C. Sarott, M. V. Westphal, Y. Mostinski, L. Mach, M. Wasinska-Kalwa, M. Weise, B. L. Hoare, T. Miljuš, M. Mexi, N. Roth, E. J. Koers, W. Guba, A. Alker, A. C. Rufer, E. A. Kusznir, S. Huber, C. Raposo, E. A. Zirwes, A. Osterwald, A. Pavlovic, S. Moes, J. Beck, M. Nettekoven, I. Benito-Cuesta, T. Grande, F. Drawnel, G. Widmer, D. Holzer, T. van der Wel, H. Mandhair, M. Honer, J. Fingerle, J. Scheffel, J. Broichhagen, K. Gawrisch, J. Romero, C. J. Hillard, Z. V. Varga, M. van der Stelt, P. Pacher, J. Gertsch, C. Ullmer, P. J. McCormick, S. Oddi, H. P. Spaink, M. Maccarrone, D. B. Veprintsev, E. M. Carreira, U. Grether, M. Nazaré, Detection of cannabinoid receptor type 2 in native cells and zebrafish with a highly potent, cell-permeable fluorescent probe. Chemical Science 13, 5539-5545 (2022), https://pubs.rsc.org/en/content/articlelanding/2022/sc/d1sc06659e.

S. Ruiz de Martín Esteban, I. Benito-Cuesta, I. Terradillos, A. M. Martínez-Relimpio, M. A. Arnanz, G. Ruiz-Pérez, C. Korn, C. Raposo, R. C. Sarott, M. V. Westphal, I. Elezgarai, E. M. Carreira, C. J. Hillard, U. Grether, P. Grandes, M. T. Grande, J. Romero, Cannabinoid CB2 Receptors Modulate Microglia Function and Amyloid Dynamics in a Mouse Model of Alzheimer’s Disease. Frontiers in Pharmacology Volume 13 (2022), https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.841766/full.

2021

M. Müller, F. Gräbnitz, N. Barandun, Y. Shen, F. Wendt, S. N. Steiner, Y. Severin, S. U. Vetterli, M. Mondal, J. R. Prudent, R. Hofmann, M. van Oostrum, R. C. Sarott, A. I. Nesvizhskii, E. M. Carreira, J. W. Bode, B. Snijder, J. A. Robinson, M. J. Loessner, A. Oxenius, B. Wollscheid, Light-mediated discovery of surfaceome nanoscale organization and intercellular receptor interaction networks. Nature Communications 12, 7036 (2021), https://www.nature.com/articles/s41467-021-27280-x#citeas.

R. C. Sarott, A. E. G. Viray, P. Pfaff, A. Sadybekov, G. Rajic, V. Katritch, E. M. Carreira, J. A. Frank, Optical Control of Cannabinoid Receptor 2-Mediated Ca2+ Release Enabled by Synthesis of Photoswitchable Probes. Journal of the American Chemical Society 143, 736-743 (2021), https://pubs.acs.org/doi/10.1021/jacs.0c08926.

2020

M. V. Westphal, R. C. Sarott, E. A. Zirwes, A. Osterwald, W. Guba, C. Ullmer, U. Grether, E. M. Carreira, Highly Selective, Amine-Derived Cannabinoid Receptor 2 Probes. Chemistry – A European Journal 26, 1380-1387 (2020), https://chemistry-europe.onlinelibrary.wiley.com/doi/10.1002/chem.201904584.

R. C. Sarott, M. V. Westphal, P. Pfaff, C. Korn, D. A. Sykes, T. Gazzi, B. Brennecke, K. Atz, M. Weise, Y. Mostinski, P. Hompluem, E. Koers, T. Miljuš, N. J. Roth, H. Asmelash, M. C. Vong, J. Piovesan, W. Guba, A. C. Rufer, E. A. Kusznir, S. Huber, C. Raposo, E. A. Zirwes, A. Osterwald, A. Pavlovic, S. Moes, J. Beck, I. Benito-Cuesta, T. Grande, S. Ruiz de Martı́n Esteban, A. Yeliseev, F. Drawnel, G. Widmer, D. Holzer, T. van der Wel, H. Mandhair, C.-Y. Yuan, W. R. Drobyski, Y. Saroz, N. Grimsey, M. Honer, J. Fingerle, K. Gawrisch, J. Romero, C. J. Hillard, Z. V. Varga, M. van der Stelt, P. Pacher, J. Gertsch, P. J. McCormick, C. Ullmer, S. Oddi, M. Maccarrone, D. B. Veprintsev, M. Nazaré, U. Grether, E. M. Carreira, Development of High-Specificity Fluorescent Probes to Enable Cannabinoid Type 2 Receptor Studies in Living Cells. Journal of the American Chemical Society 142, 16953-16964 (2020), https://pubs.acs.org/doi/10.1021/jacs.0c05587.

2017

M. V. Westphal, M. A. Schafroth, R. C. Sarott, M. A. Imhof, C. P. Bold, P. Leippe, A. Dhopeshwarkar, J. M. Grandner, V. Katritch, K. Mackie, D. Trauner, E. M. Carreira, J. A. Frank, Synthesis of Photoswitchable Δ9-Tetrahydrocannabinol Derivatives Enables Optical Control of Cannabinoid Receptor 1 Signaling. Journal of the American Chemical Society 139, 18206-18212 (2017), https://pubs.acs.org/doi/10.1021/jacs.7b06456.

2014

N. Santschi, R. C. Sarott, E. Otth, R. Kissner, A. Togni, Synthesis, characterization and initial evaluation of 5-nitro-1-(trifluoromethyl)-3H-1λ3,2-benziodaoxol-3-one. Beilstein Journal of Organic Chemistry 10, 1-6 (2014), https://www.beilstein-journals.org/bjoc/articles/10/1.

Open Positions

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