Dr. Leo Scheller
Head of Research Group | Structural Biochemistry
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. bioRxiv 2024.
Quote from Dr. Leo Scheller
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.
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 of 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.
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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:
- 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.
- Scheller, L#., Attianese, G.M.P.G#., Castellanos-Rueda, R., Di Roberto, R.B., Barden, M., Riboulet, M., Shui, S., Cribioli, E., Marchand, A., Georgeon, S., Abken, H., Reddy, S., Correia, B., Irving, M. #Equal contribution. 2024. Drug-controlled CAR-T cells through the regulation of cell-cell interactions. Preprint, bioRxiv 2024.
- Shui S, Scheller L, Correia BE. Protein-based bandpass filters for controlling cellular signaling with chemical inputs. Nature Chemical Biology 2023, 20: 586–593.
- Shui S#, Buckley S#, Scheller L#, Correia BE. #Equal contribution. Rational design of small-molecule responsive protein switches. Review, Protein Science 2023, 32:e4774.
- 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 Chemical Biology 2023, 18(6):1259–65.
- Scheller L. Synthetic Receptors for Sensing Soluble Molecules with Mammalian Cells. Book chapter, Methods in Molecular Biology 2021, 2312:15–33.
- 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. Nature Communications 2021, 12:5754
- Krawczyk K, Scheller L, Kim H, Fussenegger M. Rewiring of endogenous signaling pathways to genomic targets for therapeutic cell reprogramming. Nature Communications 2020, 30;11(1):608.
- Scheller L, Fussenegger M. From synthetic biology to human therapy: engineered mammalian cells. Review, Current Opinion in Biotechnology 2019, 58:108–16.
- Bojar D, Scheller L, Hamri GCE, Xie M, Fussenegger M. Caffeine-inducible gene switches controlling experimental diabetes. Nature Communications 2018, 9(1):2318.
- Scheller L, Strittmatter T, Fuchs D, Bojar D, Fussenegger M. Generalized extracellular molecule sensor platform for programming cellular behavior. Nature Chemical Biology 2018, 14(7):723–9.
- Kojima R, Scheller L, Fussenegger M. Nonimmune cells equipped with T-cell-receptor-like signaling for cancer cell ablation. Nature Chemical Biology 2018, 14(1):42–9.