We are exploring structured RNA as (1) a drug target and (2) a material for self-assembling nano-architectures.

(1) RNA as a Drug Target: Unique three-dimensional folds enable noncoding RNAs to participate as key players in cellular processes and provide opportunities to develop selective small molecules as inhibitors and modulators of ncRNA function. Selective ligands of ncRNA targets have a potential to expand the existing repertoire of protein-directed therapeutics. We use molecular biology and biochemistry approaches to discover and validate RNA targets, biophysical methods to study their structure and discover interactions with ligands, as well as synthetic organic chemistry to prepare and optimize RNA-binding molecules.

(2) RNA as a Material: Nucleic acid nanotechnology aims to design and build functional materials and devices that self-assemble through base pairing and folding of DNA or RNA strands. We develop crystal structure-guided design and screening approaches to create complex nucleic acid nano-architectures that self-assemble from RNA motifs as architectural joints and DNA building blocks as functional modules for modification and chemical diversification. To obtain complex soft materials, we devise additive and subtractive manufacturing techniques for self-assembling nucleic acid components.

Discovery, Validation and Screening of New RNA Targets

We use molecular biological and biochemical methods to explore new RNA targets in therapeutic areas including infectious diseases and cancer. We develop assays to discover ligands that bind to RNA targets and to study the ligands' impact on RNA biological function. Target validation aims to demonstrate feasibility for modulation or inhibition of an RNA target's function by small molecule ligands.(... more)

Structure Determination of RNA Targets and Ligand Complexes

We use X-ray crystallography to investigate the three-dimensional architecture of RNA targets and their complexes with small molecules of both natural and synthetic origin. (... more)

Design and Synthesis of New Ligands for RNA Targets

Structure-guided design is combined with ligand-based approaches to develop focused small molecule libraries for screening against RNA targets. We develop syntheses for new RNA-friendly molecules of natural product-like complexity.(... more)

Self-Assembling Nucleic Acid Nanostructures

We use crystal structures as a guide to design RNA and RNA-DNA hybrid nanostructures that self-assemble from small nucleic acid motifs and serve as combinatorial platforms for functionalization. Our lab was fist to charactrize RNA nanostructures by X-ray crystallography. One focus of our efforts in nucleic acid nanotechnology is the integration of additive and subtractive methods to enable precise nanofabrication at the sub-10nm scale. (... more)

(updated 2/2019)