Laboratory of Biomaterials and Biomolecular Systems
Precision material structures for controlling biomolecular interactions
Research overview
Well-defined and multifunctional materials are required to probe and perturb complex biological systems and improve the quality of human health. Our research broadly aims to advance active nanoscale structures and systems to study dynamic biological processes and address a variety of health-related problems. We use interdisciplinary approaches from material science, synthetic chemistry, and experimental biology to create novel enabling technologies, bridging the gap between materials development and biological/translational applications. We are interested in the fabrication of artificial structures through rational design and engineering of biomolecular building blocks that can manage interactions at the bio-nano interface and respond to spatiotemporal cues. Specific applications are exploited for early detection and monitoring of disease, profiling of multi-cellular interactions, and tool development for visualization of molecular and cellular processing in vitro and in vivo.
The research in the lab spans diverse topics that fall under three themes:
1. Identifying and probing biomarkers for cancer applications
The integration of early tumor detection and precision therapeutics for effective patient outcome highlights the need for specific and sensitive methods to detect early changes or presence of biomarkers. Although metabolic alterations are known to occur early in the precancerous stages, there are limited methods to detect its features in the complex tumor microenvironments. Relying on single type of biomarkers also remains difficult for precision diagnostics. To address this, we use synthetic approaches to develop molecular and nanoscale probes for analyzing multiple types of biomarkers present in tumor microenvironments. We aim to apply these platforms to early detection and therapeutics.
2. Engineering programmable nanostructures for profiling cellular interactions
There are gaps in characterizing molecular basis and cell-cell interactions in the microenvironments to develop timely and accurate diagnosis of cancer. Cellular interactions often involve multiple ligands, bidirectional and asymmetric, and thus requires precise control over symmetry, directionality, multi-valency at the molecular scales. We design DNA based nanostructures, with structural precision and sequence programmability to display multiple ligands with controlled molecule distance, valency, orientation, and improve their stability. We aim to apply such systems for understanding dynamic multi-cellular interactions.
3. Engineering molecular building blocks for in-situ self-assembly
Advancements in nanoparticle-based sensors and imaging have enabled non-invasive and quantitative assessments of cancer. However, nanoparticle formed ex-situ can be limited by insufficient tumor penetration and blood circulation. Emerging in-situ self-assembled nanoparticles have shown promises, however, control over the activity of monomers to only assemble at tumor sites remains challenging. We aim to engineer multi-functional building blocks that can self-assemble into supramolecular structures and exhibit collective functions at tissue sites. We synthesize peptide, mimetics, and small protein domains coupled with computational approaches, to explore the impact of sequence and structure on stability, properties and spatiotemporal control at different assembly states.
