Dr. Leo Scheller

Dr. Leo Scheller extensively worked on engineering signal transduction in mammalian cells through protein design and synthetic biology. Building on this expertise, his current work focuses on advancing immunotherapy.

Chimeric antigen receptors (CARs) and other protein-based therapeutics rely on carefully engineered proteins to redirect immune responses to treat diseases, including cancer. Dr. Scheller applies structure-guided protein design to explore new protein architectures with the potential to improve current strategies.

One major challenge for engineered immune cells is their limited ability to target solid tumors without causing on-target, off-tumor toxicity. To address this limitation, Dr. Scheller’s group develops synthetic receptors and protein therapeutics that respond to key stimuli from the tumor microenvironment, aiming to improve the specificity and efficacy of immunotherapies.

A designed chimeric antigen receptor (CAR) that can be shut off with the drug venetoclax. The drug competitively binds to bcl-2 at the same site as the designed protein LD3, causing receptor disassembly and inactivation. Scheller et al. Nature Chemical Biology, 2026.

From a structural perspective, we see cellular receptors as molecular machines that can be reprogrammed using synthetic biology and protein design. On this basis, we aim to control immune responses and enhance immunotherapies.

Dr. Leo Scheller
Head of Research Group Structural Biochemistry

Academic background and qualifications

Dr. Leo Scheller obtained his B.Sc. in Molecular Medicine from the University of Freiburg. In his final year, he participated in the iGEM synthetic biology competition, which inspired him to move to Scotland, to obtain his M.Sc. in Systems and Synthetic Biology at the University of Edinburgh. During his Ph.D. at the ETH Zürich in Switzerland, he designed a receptor platform capable of sensing disease-relevant, soluble factors, a key step toward more precise immunotherapies. His main interest lies in using synthetic biology and protein design to engineer cell signaling for biomedical applications.

Professional career

In his postdoctoral work, Dr. Scheller used computational protein design to develop switchable CARs and other biologics to enhance the safety and efficacy of immunotherapy. He first joined Prof. Bruno Correia‘s Laboratory of Protein Design and Immunoengineering at the Swiss Federal Technology Institute of Lausanne. There, he used computational protein design tools to develop small molecule-responsive chimeric antigen receptors, which he tested in collaboration with Dr. Melita Irving and Prof. George Coukos at Ludwig Cancer Research. He then joined Prof. Denis Migliorini’s Brain Tumor and Immune Cell Engineering Laboratory at the University of Geneva, located at the Agora Cancer Research Center in Lausanne, to gain expertise in translational aspects of immunotherapy research. In 2025, Dr. Scheller started the structural biochemistry group at the Leibniz Institute for Immunotherapy (LIT), focusing on cell- and protein-based therapeutics that respond to tumor-derived stimuli.

Honors

In 2021, Dr. Scheller received the Transition postdoc fellowship of the personalized health and related technologies focus area of the Swiss technical universities. In 2013, his M.Sc. in Systems and Synthetic Biology at the University of Edinburgh was awarded with distinction. Dr. Scheller is an alumnus of the German National Academic Foundation (Studienstiftung des Deutschen Volkes). In 2012 his iGEM team from the University of Freiburg received the prize for the Best New BioBrick Device, Engineered, Europe.

Explore our Research Group in greater depth

Get to know our team and find out more about our pioneering research.

Structural Biochemistry

Visit the complete publications list on GoogleScholar:

https://scholar.google.ch/citations?user=sj7sAboAAAAJ&hl=en

Here is a selection of the most important publications from the last few years:

Scheller, L.; Giordano Attianese, G. M. P.; Castellanos-Rueda, R.; Di Roberto, R. B.; Barden, M.; Triboulet, M.; Hafezi, M.; Ash, S.; Shui, S.; Cribioli, E.; Reichenbach, P.; Maillard, J.; Marchand, A.; Georgeon, S.; Wolf, B.; Abken, H.; Reddy, S.; Correia, B. E.; Irving, M. Drug-Controlled CAR T Cells through the Regulation of Cell–Cell Interactions. Nat Chem Biol 2026, 1–12. https://doi.org/10.1038/s41589-026-02152-x.
Si, Y.; Fan, Y.; Scheller, L.; Stefanov, B.-A.; Lv, J.; Wang, Z.; Xie, M.; Fussenegger, M. Engineering Mammalian Cells for Detection and Treatment of Cardiac Injury. Mol Syst Biol 2026, 22 (1), 88–101. https://doi.org/10.1038/s44320-025-00161-x.
Marchand, A.; Buckley, S.; Schneuing, A.; Pacesa, M.; Elia, M.; Gainza, P.; Elizarova, E.; Neeser, R. M.; Lee, P.-W.; Reymond, L.; Miao, Y.; Scheller, L.; Georgeon, S.; Schmidt, J.; Schwaller, P.; Maerkl, S. J.; Bronstein, M.; Correia, B. E. Targeting Protein–Ligand Neosurfaces with a Generalizable Deep Learning Tool. Nature 2025, 639 (8054), 522–531. https://doi.org/10.1038/s41586-024-08435-4.
Giordano Attianese, G. M. P.; Shui, S.; Cribioli, E.; Triboulet, M.; Scheller, L.; Hafezi, M.; Reichenbach, P.; Gainza, P.; Georgeon, S.; Correia, B. E.; Irving, M. Dual ON/OFF-Switch Chimeric Antigen Receptor Controlled by Two Clinically Approved Drugs. Proc. Natl. Acad. Sci. U.S.A. 2024, 121 (44), e2405085121. https://doi.org/10.1073/pnas.2405085121.
Shui, S.; Scheller, L.; Correia, B. E. Protein-Based Bandpass Filters for Controlling Cellular Signaling with Chemical Inputs. Nat Chem Biol 2024, 20 (5), 586–593. https://doi.org/10.1038/s41589-023-01463-7.
Marchand, A.; Bonati, L.; Shui, S.; Scheller, L.; Gainza, P.; Rosset, S.; Georgeon, S.; Tang, L.; Correia, B. E. Rational Design of Chemically Controlled Antibodies and Protein Therapeutics. ACS Chem. Biol. 2023, 18 (6), 1259–1265. https://doi.org/10.1021/acschembio.3c00012.
Shui, S.; Buckley, S.; Scheller, L.; Correia, B. E. Rational Design of Small‐molecule Responsive Protein Switches. Protein Science 2023, 32 (10), e4774. https://doi.org/10.1002/pro.4774.
Strittmatter, T.; Wang, Y.; Bertschi, A.; Scheller, L.; Freitag, P. C.; Ray, P. G.; Stuecheli, P.; Schaefer, J. V.; Reinberg, T.; Tsakiris, D.; Plückthun, A.; Ye, H.; Fussenegger, M. Programmable DARPin-Based Receptors for the Detection of Thrombotic Markers. Nat Chem Biol 2022, 18 (10), 1125–1134. https://doi.org/10.1038/s41589-022-01095-3.
Shui, S.; Gainza, P.; Scheller, L.; Yang, C.; Kurumida, Y.; Rosset, S.; Georgeon, S.; Di Roberto, R. B.; Castellanos-Rueda, R.; Reddy, S. T.; Correia, B. E. A Rational Blueprint for the Design of Chemically-Controlled Protein Switches. Nat Commun 2021, 12 (1), 5754. https://doi.org/10.1038/s41467-021-25735-9.
Yang, C.; Sesterhenn, F.; Bonet, J.; van Aalen, E. A.; Scheller, L.; Abriata, L. A.; Cramer, J. T.; Wen, X.; Rosset, S.; Georgeon, S.; Jardetzky, T.; Krey, T.; Fussenegger, M.; Merkx, M.; Correia, B. E. Bottom-up de Novo Design of Functional Proteins with Complex Structural Features. Nat Chem Biol 2021, 17 (4), 492–500. https://doi.org/10.1038/s41589-020-00699-x.
Scheller, L.; Schmollack, M.; Bertschi, A.; Mansouri, M.; Saxena, P.; Fussenegger, M. Phosphoregulated Orthogonal Signal Transduction in Mammalian Cells. Nat Commun 2020, 11 (1), 3085. https://doi.org/10.1038/s41467-020-16895-1.

Dr. Leo Scheller
Head of Research Group | Structural Biochemistry

Email: leo.scheller@lit.eu