Department of Biochemistry and Molecular Biology
Georgia Cancer Center
1410 Laney Walker Blvd., CN 2132
The goals of our research are to develop nucleic acid-based aptamer/siRNA therapeutics for cancer targeted treatment, and to develop new nanomaterials and methodologies for probing disease markers at single-cell and single-molecule levels.
Development of multifunctional chimeras for cancer treatment.
We have great interests in integrating aptamer and siRNA into cancer treatment. siRNAs have potential to knock down all protein expression. Nucleic acid aptamers, often termed chemical antibodies, are single-stranded DNA or RNA molecules that can specifically bind to targets via 3-D structures. Aptamers are developed from a reiterative process called Systematic Evolution of Ligands by Exponential enrichment (SELEX). Compared with antibodies, aptamers are easy in vitro production and modification, low cost, low immunogenicity, and thermostable. Many aptamers bind to a specific protein and also inhibit its function. Some aptamers enable cell-type specific siRNA delivery. We are developing new chimeras by targeting tumorigenesis-related molecules, and developing multi-functional chimeras for tumor combination treatment. With aptamer-siRNA chimeras, we are addressing currently “undruggable” cancer therapeutic targets.
In recent studies, we have developed: 1) a HER family-targeted chimera which can reduce protein expression of EGFR/HER2/HER3; 2) a bispecific CD44-EpCAM aptamer which can specifically bind to spread ovarian tumors but not normal tissues;3) a bivalent aptamer-dual siRNA by targeting EGFR and survivin for prostate cancer treatment.
The current work will focus on the synthesis of protein-based vectors for siRNA delivery, and advance technologies on construction of multifunctional aptamer-siRNA chimeras for cancer treatment. We also will use SELEX technology to generate and optimize new oncogene-targeted aptamers.
Quantum dots (QDs), light-emitting nanocrystals, possess unique properties such as size-tunable emission, super brightness, and photo-stable. We are developing new QD probes and the methodologies for biomarker profiling and quantitation. Exosomes, small vesicles (50-200nm), secreted by cells have been as “liquid biopsies” for real-time monitoring disease progression. Tumor-derived exosomes resemble that of the cell of origin and are highly enriched with tumor biomarkers. Our goal is to develop Membrane-Based Single-Molecule Counting (M-SMC) technology for exosome biomarker profiling. M-SMC will use our engineered accurate monovalent QD probes and invented transparent PVDF membrane.