Research projects

Engineering Applications of 3D Printing in Drug Discovery Laboratories

Beyond its role in pharmaceutical formulation, 3D printing offers significant engineering opportunities for the design and fabrication of customized laboratory equipment and research devices. Additive manufacturing enables rapid prototyping of bespoke components such as microfluidic chips, reaction vessels, syringe pumps, vial holders, filtration units, and modular flow-reactor housings. This flexibility allows laboratories to tailor experimental setups precisely to specific research needs without reliance on expensive commercial hardware. Complex geometries that would be difficult or costly to machine—such as internal channels, integrated connectors, or multi-compartment systems—can be produced efficiently using modern printing techniques. Materials ranging from chemically resistant polymers to high-temperature resins expand compatibility with synthetic and analytical workflows. In medicinal chemistry and chemical biology, printed devices can support miniaturized reaction screening, parallel synthesis, and automated sample handling. Integration with electronics further enables the construction of sensor-equipped platforms and custom analytical interfaces. Importantly, rapid iteration cycles reduce development time for experimental apparatus and encourage innovation at the bench level. By decentralizing device fabrication and empowering researcher-driven engineering solutions, 3D printing has the potential to reshape the infrastructure of drug discovery laboratories.

Exploring the Chemical Space of E3 Ligase Binders: Functionalization, Exit Vectors, and Ligase Diversity

Although the human genome encodes more than 600 E3 ligases, drug discovery efforts have predominantly focused on a small subset, particularly CRBN and VHL. This limited utilization reflects the narrow chemical space currently occupied by validated E3 ligase binders. A systematic exploration of E3 binder chemical diversity is therefore essential to broaden the applicability of targeted protein degradation strategies. Key objectives include mapping scaffold diversity, three-dimensional shape distribution, and physicochemical properties across known and newly discovered ligands. Functionalization tolerance must be characterized in detail to determine viable exit vectors that permit linker attachment without compromising binding affinity. Structural methods such as X-ray crystallography and cryo-electron microscopy can define how modifications influence ligase engagement and ternary complex formation. Chemoproteomic and fragment-based approaches may reveal novel ligandable pockets across underexplored ligases. Expanding ligase diversity could enable tissue-specific or disease-context-dependent degradation by leveraging differential ligase expression patterns. Overall, this research aims to systematically define and expand the chemical and functional landscape of E3 ligase binders to unlock the full therapeutic potential of targeted degradation.

Combinatorial Design Principles for Modular PROTAC Assembly: E3 Ligase Binders, Linkers, and POI Ligands

Proteolysis-targeting chimeras (PROTACs) represent a transformative modality in drug discovery by enabling selective degradation of disease-relevant proteins rather than simple inhibition. Despite their conceptual modularity—comprising an E3 ligase binder, a linker, and a protein-of-interest (POI) ligand—their design remains largely empirical. A combinatorial framework for PROTAC assembly seeks to systematically explore the design space generated by varying these three components. In the future such an approach would allow structured investigation of how linker length, rigidity, polarity, and attachment geometry influence ternary complex formation and degradation efficiency. Importantly, degradation is governed not only by binary affinity but also by cooperativity and productive ubiquitination kinetics. High-throughput synthetic strategies could enable rapid generation of modular libraries. Integration of structural biology and computational modeling would further refine predictive capabilities for ternary complex geometry. Ultimately, this research direction aims to transition PROTAC development from empirical optimization to rational, design-driven engineering of degraders.

Chemical and Biophysical Characterization of RNA-Binding Small Molecules

Targeting RNA with small molecules represents a promising yet comparatively underdeveloped area of drug discovery. Unlike proteins, RNA molecules often exhibit high conformational flexibility, shallow binding pockets, and dense negative charge distributions, complicating selective ligand design. Historically, many RNA-binding compounds have been intercalators or highly charged scaffolds with limited specificity. Advancing this field requires detailed chemical and biophysical characterization of RNA–ligand interactions. Techniques such as NMR spectroscopy, SHAPE-based structural probing, and cryo-EM provide insights into binding modes and conformational effects. Transcriptome-wide profiling approaches are essential to assess selectivity and avoid off-target interactions. Computational modeling of RNA conformational ensembles can aid in identifying transient but druggable pockets. Improving physicochemical balance to maintain cellular permeability while preserving affinity remains a central challenge. Collectively, these efforts aim to transform RNA targeting from opportunistic discovery into a rational, structure-guided therapeutic strategy.