Liwei Zheng

Massively parallel DNA sequencing has transformed the study of genomes and transcriptomes, enabling biological discovery at unprecedented scale and depth. In our research lab, we believe that DNA sequencing technologies can also be used to read out biological signals beyond DNA and RNA. Our goal is to develop new chemical tools that connect these diverse biological signals to high-throughput DNA sequencing platforms, thereby addressing challenging bioanalytical problems. We are particularly interested in: (1) developing methods and strategies for single-molecule protein sequencing; (2) establishing rational DNA aptamer engineering through sequencing-based DNA aptamer structure profiling; and (3) advancing sequencing-based metabolomics.

Single-Molecule Protein Sequencing

Proteins are the workhorses of the cell, and their abundance, composition, and molecular states provide direct insight into cellular function in both health and disease. Our group develops new chemistries and analytical strategies that convert protein sequence information into DNA-encoded signals readable by high-throughput sequencing platforms. By enabling de novo protein analysis at single-molecule and single-amino-acid resolution, these technologies could reveal previously inaccessible biology and create new opportunities for disease research, biomarker discovery, and therapeutic development.

Sequencing-Based DNA Aptamer Structure Profiling and Structure-Guided Aptamer Design

Aptamers are short oligonucleotides that bind specific targets, and their stability, accessibility, and chemical versatility make them powerful recognition elements for bioassays and biosensors. However, DNA aptamer engineering remains limited by the lack of scalable methods for structural characterization. Our lab develops high-throughput approaches to profile the secondary and tertiary structures of DNA aptamers. By revealing how aptamers fold and recognize their targets, these technologies could enable more rational biosensor design and deepen our understanding of single-stranded DNA structure and function.

Metabolomics via DNA Sequencing

Metabolites are direct indicators of cellular activity and physiological state, but their chemical diversity and wide dynamic range make comprehensive analysis challenging. Our lab develops molecular recognition and signal-transduction strategies that convert metabolite concentrations into DNA-encoded signals readable by high-throughput sequencing. By coupling small-molecule recognition with amplifiable DNA barcodes, these technologies could enable sensitive and highly multiplexed metabolite quantification. Ultimately, sequencing-based metabolomics may facilitate integrated single-cell and spatial analysis of metabolites alongside genomic and transcriptomic information.