Guido Papa

Cells are not simply containers of molecules, but highly organised systems in which proteins dynamically assemble to perform specific functions. Understanding how these cluster form, are regulated, and disassemble represents one of the central challenges of modern biology and a new frontier for the development of innovative therapies.
The Targeted Protein Degradation laboratory (TPD-Lab, for friends) studies the fundamental principles that govern the organisation of intracellular space and the control of protein function, with a particular focus on biomolecular condensates and targeted degradation technologies that can modulate these structures. The goal is to understand how these processes contribute to cellular physiology and how their dysregulation underlies a wide range of diseases.
Biomolecular condensates are dynamic, membrane-less cellular compartments that form through multivalent interactions between proteins and nucleic acids, creating specialised microenvironments with distinct physical properties compared to the surrounding cytoplasm or nucleus. These structures enable the concentration, organisation, and regulation of biochemical reactions in a rapid and reversible manner, coordinating essential processes such as gene expression, stress response, and replication. Alterations in their formation, composition, or dynamics are increasingly recognised as key drivers of various diseases, including viral infections, cancer, neurodegenerative disorders, and genetic diseases.
In parallel, targeted protein degradation is redefining how protein function can be manipulated inside cells. These technologies allow the selective elimination of specific proteins, including those traditionally considered “undruggable,” offering new opportunities beyond conventional inhibition-based approaches.
We use viruses as model systems to study the formation and function of these assemblies and to develop protein degradation strategies capable of selectively targeting them. By profoundly remodelling the cellular environment, viruses generate highly organised structures that serve as ideal systems to investigate these processes at the biochemical, cellular, and molecular levels. This approach allows us to uncover general principles governing protein assembly and organisation that are transferable to a wide range of diseases characterized by aberrant protein aggregation.
By combining cell biology, biochemistry, and drug discovery, we aim to define the mechanisms that regulate the assembly and dynamics of condensates and to develop strategies to disassemble or reprogram them through targeted protein degradation.
Our ultimate goal is to translate these principles into new therapeutic strategies capable of targeting the molecular organisation of the cell, with broad implications across multiple human diseases.
Curious to learn more? Visit our website and explore our research in detail:
papalab.unimi.it