Cancer Immunology, Inflammation & Tolerance


Hongyan LiuHong Yan Liu, PhD

Assistant Professor
Department of Biochemistry and Molecular Biology
 

Georgia Cancer Center
1410 Laney Walker Blvd., CN 2132
Office: 706-721-7149
Lab: 706-721-3933
holiu@augusta.edu

 

Research Summary

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.

Research Interests

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.

Biomarker profiling.

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.

Recent Publications

  1. Yu X, Ghamande S, Liu H, Xue L, Zhao S, Tan W, Zhao L, Tang SC, Wu D, Korkaya H, Maihle NJ, Liu HY. Targeting EGFR/HER2/HER3 with a Three-in-One Aptamer-siRNA Chimera Confers Superior Activity against HER2+Breast Cancer. Molecular therapy Nucleic acids. 2018; 10:317-330.
  2. Zheng J, Zhao S, Yu X, Huang S, Liu HY. Simultaneous targeting of CD44 and EpCAM with a bispecific aptamer effectively inhibits intraperitoneal ovarian cancer growth. Theranostics. 2017; 7(5):1373-1388.
  3. Liu HY. Bivalent aptamer-dual siRNA chimera is emerging as a new combination therapy. RNA & DISEASE. 2017 April 10; 4 ( Review)
  4. Liu HY, Yu X, Liu H, Wu D, She JX. Co-targeting EGFR and survivin with a bivalent aptamer-dual siRNA chimera effectively suppresses prostate cancer. Scientific reports. 2016; 6:30346. Corresponding author.
  5. Liu HY, Zrazhevskiy P, Gao X. Solid-phase bioconjugation of heterobifunctional adaptors for versatile assembly of bispecific targeting ligands. Bioconjugate chemistry. 2014; 25(8):1511-6.
  6. Liu HY, Gao X. A universal protein tag for delivery of SiRNA-aptamer chimeras. Scientific reports. 2013; 3:3129.
  7. Liu HY, Gao X. Engineering monovalent quantum dot-antibody bioconjugates with a hybrid gel system. Bioconjugate chemistry. 2011; 22(3):510-7.
  8. Scholl B, Liu HY, Long BR, McCarty OJ, O'Hare T, Druker BJ, Vu TQ. Single particle quantum dot imaging achieves ultrasensitive detection capabilities for Western immunoblot analysis. ACS nano. 2009; 3(6):1318-28.
  9. Vu TQ, Liu HY. Quantum dot hybrid gel blotting: a technique for identifying quantum dot-protein/protein-protein interactions. Methods in molecular biology. 2009; 544:381-91.
  10. Rajan SS, Liu HY, Vu TQ. Ligand-bound quantum dot probes for studying the molecular scale dynamics of receptor endocytic trafficking in live cells. ACS nano. 2008; 2(6):1153-66.
  11. Liu HY, Zheng G, Zhu H, Woldegiorgis G. Hormonal and nutritional regulation of muscle carnitine palmitoyltransferase I gene expression in vivo. Archives of biochemistry and biophysics. 2007; 465(2):437-42.
  12. Liu HY, Vu TQ. Identification of quantum dot bioconjugates and cellular protein co-localization by hybrid gel blotting. Nano letters. 2007; 7(4):1044-9.
  13. Vu TQ, Rajan SS, Liu H. Ligand-bound quantum dots for intracellular imaging of neural receptors. SPIE. 2007; 6448:644813.
  14. Pejovic T, Yates JE, Liu HY, Hays LE, Akkari Y, Torimaru Y, Keeble W, Rathbun RK, Rodgers WH, Bale AE, Ameziane N, Zwaan CM, Errami A, Thuillier P, Cappuccini F, Olson SB, Cain JM, Bagby GC Jr. Cytogenetic instability in ovarian epithelial cells from women at risk of ovarian cancer. Cancer research. 2006; 66(18):9017-255.
  15. Liu H, Zheng G, Treber M, Dai J, Woldegiorgis G. Cysteine-scanning mutagenesis of muscle carnitine palmitoyltransferase I reveals a single cysteine residue (Cys-305) is important for catalysis. The Journal of biological chemistry. 2005; 280(6):4524-31
  16. Liu HY, Buenafe AC, Matejuk A, Ito A, Zamora A, Dwyer J, Vandenbark AA, Offner H. Estrogen inhibition of EAE involves effects on dendritic cell function. Journal of neuroscience research. 2002; 70(2):238-48.