Research Synopsis

Biopharmaceuticals and chemical biology: systematic development and translational application of theranostic targeting molecules from various protein domain or unnatural nucleic acid libraries using directed evolution and selection strategies, identification of proteins with desired functions from natural proteome libraries and elucidation of the related signaling pathways, targeted delivery of theranostic molecules to diseased tissues; cancer nanotechnology

Rihe Liu received his bachelor’s degree in polymer physics from the University of Science and Technology of China in 1988. He did his graduate work from 1992 to 1996 with Professor Leslie E. Orgel at the Salk Institute for Biological Studies and received his PhD in biochemistry from the University of California at San Diego. He carried out postdoctoral work from 1997 to 2001 with Professor Jack W. Szostak at Massachusetts General Hospital and Harvard Medical School before joining the faculty at the University of North Carolina at Chapel Hill in December 2001. He is currently an associate professor at the Division of Chemical Biology and Medicinal Chemistry at the UNC Eshelman School of Pharmacy and an associate professor at the Carolina Center for Genome Sciences at UNC School of Medicine.

Research Interests

The Rihe Liu group's interests include

1. the systematic development of clinically amenable targeting ligands that tightly and highly specifically bind to biomarkers on the surface of cancer cells from protein domain libraries and nuclease-resistant nucleic acid libraries with unusually high diversity;
2. the identification of natural and synthetic proteins with desired biological functions and elucidation of the related protein-protein, enzyme-substrate, and drug-target interaction networks at a proteome-wide scale using combinatorial biochemistry and chemical biology approaches.

The group is particularly interested in developing novel cancer biomarker-binding theranostic molecules that are based on the single domain antibodies or their mimics with human origins using sophisticated protein display technologies. They are also developing cancer biomarker-binding affinity molecules that are based on the nuclease-resistant nucleic acid aptamers using a combination of conventional SELEX, cell-SELEX, and in vivo SELEX technology platforms. The resulting targeting ligands are further engineered to have desired multispecificity and avidity and applied in translational research using xenograft, orthotopic, and patient-derived animal models.

Ten Most Recent Publications

1. mRNA display-based selections using synthetic peptide and natural protein libraries. Cotten SW, Zou J, Wang R, Huang BC, Liu R. Methods Mol Biol. 2012;805:287-97. PMID: 22094812 [PubMed - in process]

2. mRNA display using covalent coupling of mRNA to translated proteins. Wang R, Cotten SW, Liu R. Methods Mol Biol. 2012;805:87-100. PMID: 22094802 [PubMed - in process]

3. In vitro and in vivo assessment of targeting lipid-based nanoparticles to the epidermal growth factor-receptor (EGFR) using a novel Heptameric Z(EGFR) domain. Benhabbour SR, Luft JC, Kim D, Jain A, Wadhwa S, Parrott MC, Liu R, Desimone JM, Mumper RJ. J Control Release. 2011 Oct 20. [Epub ahead of print] PMID: 22037106 [PubMed - as supplied by publisher]

4.Selection of proteins with desired properties from natural proteome libraries using mRNA display. Cotten SW, Zou J, Valencia CA, Liu R. Nat Protoc. 2011 Jul 21;6(8):1163-82. doi: 10.1038/nprot.2011.354. PMID: 21799486 [PubMed - indexed for MEDLINE]

5. Identification of a lacosamide binding protein using an affinity bait and chemical reporter strategy: 14-3-3 ζ. Park KD, Kim D, Reamtong O, Eyers C, Gaskell SJ, Liu R, Kohn H. J Am Chem Soc. 2011 Jul 27;133(29):11320-30. Epub 2011 Jul 6. PMID: 21692503 [PubMed indexed for MEDLINE]

6. Advantages of mRNA display selections over other selection techniques for investigation of protein-protein interactions. Wang H, Liu R. Expert Rev Proteomics. 2011 Jun;8(3):335-46. Review. PMID: 21679115 [PubMed - indexed for MEDLINE]

7. Lacosamide isothiocyanate-based agents: novel agents to target and identify lacosamide receptors. Park KD, Morieux P, Salomé C, Cotten SW, Reamtong O, Eyers C, Gaskell SJ, Stables JP, Liu R, Kohn H. J Med Chem. 2009 Nov 12;52(21):6897-911. PMID: 19795888 [PubMed - indexed for MEDLINE]

8. Morphing low-affinity ligands into high-avidity nanoparticles by thermally triggered self-assembly of a genetically encoded polymer. Simnick AJ, Valencia CA, Liu R, Chilkoti A. ACS Nano. 2010 Apr 27;4(4):2217-27. PMID: 20334355 [PubMed - indexed for MEDLINE]

9. Proteomic searches comparing two (R)-lacosamide affinity baits: An electrophilic arylisothiocyanate and a photoactivated arylazide group. Park KD, Stables JP, Liu R, Kohn H. Org Biomol Chem. 2010 Jun 21;8(12):2803-13. Epub 2010 Apr 19. PMID: 20405068 [PubMed - indexed for MEDLINE]

10. Development and characterization of novel derivatives of the antiepileptic drug lacosamide that exhibit far greater enhancement in slow inactivation of voltage-gated sodium channels. Wang Y, Park KD, Salome C, Wilson SM, Stables JP, Liu R, Khanna R, Kohn H. ACS Chem Neurosci. 2011 Feb 16;2(2):90-106. PMID: 21532923 [PubMed]