Publications

Lab Research Interests and Supports

The general interests of the laboratory are at the interface of organic chemistry, biochemistry and molecular biology.

Nucleic Acid plays the most important roles in living organisms. To understand how nucleic acid behaves in vitro and in vivo is essential. Our research will integrate chemical synthetic skills, enzymatic methods, and molecular biology techniques to better understand structural properties and molecular mechanisms of these types of macromolecules. Current projects are related to synthesis of analogs of nucleosides and nucleotides, derivatization of nucleic acids for DNA and RNA X-ray crystal structure studies, in vitro and in vivo selection and evolution of ligand-binding and catalytic RNAs, ribozyme gene therapy, and direct quantitation of gene expression.

DNA & RNA Derivatization Project: X-ray crystallography is a powerful tool for structure determination of RNA structure, RNA-protein and DNA-protein complexes with high resolution. Derivatization with heavy atoms for phase determination, a long-standing problem in X-ray crystallography, however, has largely slowed down structural determination of nucleic acids with novel folds. One approach to facilitate the structure determination is to label nucleic acids with covalently linked heavy atoms, which enable phase and structure determination. We have developed a new strategy to derivatize RNA and DNA using selenium and the principle has been demonstrated by X-ray crystallography using MAD phasing method.

RNA Detection & Quantitation Project: Rapid research progress in genome sequence and function has facilitated drug discovery and revealed more insights on infection, disease mechanism, and cancer subtype via gene expression profiling. My laboratory has recently developed a novel RNA detection and quantification method, which involves the RNA 3’-terminal labeling. This specific labeling and detection approach have lead to an RNA detection method on microplate via immobilization of the hybrid template. The microplate format dramatically simplifies the experimental procedure. The goals of this project are: (I) further development of RNA direct detection and quantification for multiple gene expression analysis, (II) development of RNA microchip technology on the basis of this novel strategy, (III) gene expression profiling with the RNA microchip technology, (IV) pathogen, bio-contaminant, and disease rapid analysis using the RNA microchip technology. It is envisioned that this RNA microchip technology will be simple, rapid, accurate, sensitive, high-throughput, and cost-effective and that it will be an ideal approach for pathogen detection in biodefense, drug target validation and development, point-of-care disease diagnosis, SNP analysis, and detection of closely-related microorganisms in air, soil, food, and water supply.

Advantages and Potentials of RNA MicroChip Technology

·          Doesn’t need antibody for target recognition, PCR or reverse transcription

·          No laser excitation and fluorescence detection

·          No radioactive labeling, or gel electrophoresis

·          RNA detection via chemiluminescence

·          Detection of closely-related microorganisms

·          Simple, rapid, direct, sensitive, and accurate

·          Suitable for analysis of environmental samples even where mRNAs are partially degraded.

These research projects have been supported by

        National Institute of General Medical Sciences (NIGMS), NIH (Priority Score: 127)

        Pfizer, Inc.

        Glen Research, Inc.

        Dharmacon Research, Inc.

        New Research Dimension, Inc.

        PSC-CUNY      

        CUNY Collaborative Program

        CUNY Groundwork Award