Georg Winter is an international award-winning scientist, ERC prize winner and co-founder of start-up companies. Georg Winter’s work in targeted protein degradation is not only advancing fundamental research but also paving the way for practical applications.
Georg Winter - Scientific Director LS
Biosketch
Georg Winter = Curious, Optimistic, Impatient, Empathic, Ambitious
Georg Winter performed his graduate studies at CeMM in Vienna, working on elucidating the mechanism of action of cancer drugs with a specific emphasis on proteomics- as well as chemical genetics approaches. He continued his training in chemical biology, working as a postdoctoral fellow with Dr. James Bradner the Dana Farber Cancer Institute where he published the first paper reporting on in vivo target protein degradation and co-developed degron-tagging approaches that leverage the E3 ligase CRBN (dTAG approach) to understand the mechanistic involvement of gene control factors in oncogenic transcriptional circuits. He was recruited as a CeMM Principal Investigator in June 2016, continuing his work on targeted protein degradation with a particular emphasis on the phenotypic identification and mechanistic characterization of molecular glue degraders. In April 2025, Georg has been appointed as the Life Science Director at AITHYRA.
The Winter lab has been funded via several national and international third-party grants, including two ERC Grants (Starting and Consolidator), an Aspire Award (Mark Foundation) and a Cancer Grand Challenge Award.
Georg has authored more than 60 peer-reviewed papers and his contributions to the field of chemical biology in general, as well as targeted protein in particular, have been recognized via several international awards including the Eppendorf Award for Young European Investigators, the Wilson S. Stone Memorial Award from the MD Anderson, the Tetrahedron Young Investigator Award and the EFMC Price for Young Chemical Biologists.
Orchid number: https://orcid.org/0000-0001-6606-1437
LinkedIn: https://www.linkedin.com/in/georg-winter-a2145358/
Website: https://www.winter-lab.com/
Research
Understanding and Reprogramming Biological Circuits With Chemistry
Thematically, we work at the interface of chemical biology, proteostasis, and gene control. We aim to innovate novel chemical strategies that allow us to better understand fundamental principles of small-molecule action on transcription regulation and the ubiquitin-proteasome system. In particular, we are fascinated by the concept of chemical neomorphs: small molecules that can endow proteins with novel functions to ultimately rewire cellular circuits. Our current focus is on small-molecule degraders, which induce proximity between a target protein of interest and an E3 ubiquitin ligase to prompt ubiquitination and proteasomal degradation of the target protein. In addition, we are keen to expand this concept towards other cellular functions, particularly focusing on small molecules that can functionally hijack transcriptional circuits, signaling or the DNA damage response. In order to discover chemical neomorphs, we frequently conduct phenotypic screens followed by mechanistic workup. We are thus excited about innovating and implementing cutting-edge technology that informs on principles of how small molecules interact with native biological systems. These studies are frequently driven by high-throughput and unbiased technologies such as quantitative proteomics, transcriptomics and particularly functional genomics. We are further excited to augment the interpretability of these large-scale datasets via artificial intelligence and machine learning methods. Connecting the derived insights with synthetic chemistry enables us to understand the mechanism of action of proteins, protein complexes or small molecules both on a holistic but also mechanistic level. In addition, we plan to leverage AI/ML to systematically move from phenotypic discovery to purposeful design of chemical neomorphs.
Our ultimate vision is that the fundamental insights that our work uncovers will contribute to therapeutic innovation that is built on the thesis of rewiring or (re-)programming of biological circuits.
Targeted Protein Degradation and other proximity-inducing approaches
The innovation of pharmacologic strategies to prompt degradation of target proteins has been a long-standing challenge in the field. Towards a scalable, and rational strategy for ligand-induced destabilization of proteins, we developed heterobifunctional small-molecules by conjugating a phthalimide moiety to competitive antagonists of BET bromodomain proteins via a short, aliphatic linker. These compounds were the first PROTACs to show efficacy in vivo and prompted a widespread interest in the biopharmaceutical industry (Winter, Science 2015). Over the last years (supported by an ERC Starting Grant), research in my lab has been focused on developing methods to identify and mechanistically characterize monovalent and drug-like molecular glue degraders. This has led to the identification of degraders against otherwise undruggable proteins, such as Cyclin K (Mayor-Ruiz, Nature Chemical Biology 2020), has allowed us to functionally hijack a range of different E3 ligases, including DCAF11 and FBOX22 (Xue, Nature Communications, 2023; Kagiou, Nature Communications, 2024), and has also revealed a new modality in targeted protein degradation: intramolecular, bivalent glue degraders (Hsia, Hinterndorfer, Cowan, Nature 2024). Most recently, we have been interested in decoding how (and how often) inhibitors can induce target degradation (Scholes, Nature 2025). Moving ahead (supported by an ERC Consolidator Grant), my group seeks to apply our know-how in protein degradation to identify pharmacologic approaches to re-wire additional biological circuits.
Publication Highlights
Large-scale chemoproteomics expedites ligand discovery and predicts ligand behaviour in cells. Offensperger F, Tin G, Duran-Frigola M, Hahn E, Dobner S, am Ende CW, Strohbach JW, Rukavina A, Brennsteiner V, Ogilvie K, Marella N, Kladnik K, Ciuffa R, Majmudar JD, Field SD, Bensimon A, Ferrari L, Ferrada E, Ng A, Zhang Z, Degliesposti G, Boeszoermenyi A, Martens S, Stanton R, Mueller A, Hannich JT, Hepworth D, Superti-Furga G, Kubicek S, Schenone M, Winter GE. Science 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864
Targeted protein degradation via intramolecular bivalent glues. Hsia O, Hinterndorfer M, Cowan AD, Iso K, Ishida T, Sundaramoorthy R, Nakasone MA, Imrichova H, Schätz C, Rukavina A, Husnjak K, Wegner M, Correa-Sáez A, Craigon C, Casement R, Maniaci C, Testa A, Kaulich M, Dikic I, Winter GE*, Ciulli A*. Nature. 2024 Mar;627(8002):204-211. doi: 10.1038/s41586-024-07089-6
Phthalimide conjugation as a strategy for in vivo target protein degradation. Winter GE, Buckley DL, Paulk J, Roberts JM, Souza A, Dhe-Paganon S, Bradner JE. DRUG DEVELOPMENT. Science. 2015 Jun 19;348(6241):1376-81. doi:10.1126/science.aab1433
Section
The Winter Lab Team
Recent Publications
2025
Protein palmitoylation and sphingolipid metabolism control regulated exocytosis in cytotoxic lymphocytes
Regulated exocytosis controls key cellular functions ranging from neurotransmitter release to the secretion of immune mediators, and its disruption is associated with numerous pathologies. The cytotoxic activity of lymphocytes is particularly dependent on regulated and polarized lytic granule delivery toward infected or malignant cells. Although genetic and mechanistic studies have identified factors regulating exocytosis in cytotoxic lymphocytes, a systematic mapping of the relevant factors and...
2025
Targeted protein degradation for cancer therapy
Targeted protein degradation (TPD) aims at reprogramming the target specificity of the ubiquitin-proteasome system, the major cellular protein disposal machinery, to induce selective ubiquitination and degradation of therapeutically relevant proteins. Since its conception over 20 years ago, TPD has gained a lot of attention mainly due to improvements in the design of bifunctional proteolysis targeting chimeras (PROTACs) and understanding the mechanisms underlying molecular glue degraders. Today,...
2025
Opportunities in proximity modulation: Bridging academia and industry
In the past decade, exciting therapeutic strategies to harness the ubiquitin-proteasome system (UPS) for degradation of target proteins have emerged. Proximity-inducing modalities are at the center of these strategies and act by modulating protein-protein interactions. While we are still learning to harvest this approach, it holds tremendous promise for developing treatments for hitherto undruggable proteins. Here, we discuss how academic efforts and academic-industrial collaboration have...