Academic Profile

Academic Profile

Assoc Prof Li Tianhu

Associate Professor, School of Physical & Mathematical Sciences

Email: thli@ntu.edu.sg
Phone: +65 65137364
Office: SPMS-CBC 04 21
Assoc Prof Li Tianhu

Biography
Associate Professor Li Tianhu has joined the School of Physical & Mathematical Sciences in May 2008. Dr Li completed his undergraduate studies in Department of Chemistry at Jilin University with polymer chemistry major in 1980 and obtained his Master Degree under the supervision of Professor Jin Guan Tai at Beijing Institute of Chemical Technology in 1982. After working at the same institute for more than three years, Dr. Li went to The United States and obtained his Ph. D. degree under the supervision of Professor Steven Rokita in Department of Chemistry at State University of New York at Stony Brook in 1992. The focus of his graduate research work was on development of new type of antisense oligonucleotides. From 1992 to 1994, Dr. Li had been a postdoctoral research associate under the supervision of Professor K. C. Nicolaou at the Scripps Research Institute working on chemical evolution of life and characterization of the interaction between DNA and small molecules. He then took a faculty member in Department of Pharmacology at University of Pittsburgh in 1994 and worked on topoisomerase I inhibitors. After staying in Pittsburgh for a year and half, Dr. Li took an assistant professor position in Department of Chemistry at The Scripps Research Institute under Professor KC Nicolaou’s domain in January 1996. Starting from 1999, Dr. Li had worked as senior research fellow and professorial fellow in Hong Kong Polytechnic University for five years. Dr. Li then took an associate professor position offered by Department of Chemistry at National University of Singapore before joining Nanyang Technological University.

Dr Li's research interests are mainly on nucleic acid chemistry in areas like deoxyribozyme, G-quadruplex, i-motif, and supercoiled DNA. He has done significant research work in these areas and has published many journal papers. Recently, one of Dr Li's group discovery is also published on Chemical Biology on January 2008.
Research Interests
Associate Professor Li Tianhu's areas of expertise are nucleic acid chemistry (deoxyribozyme, G-quadruplex, i-motif, supercoiled DNA). His current research focuses are mainly on the following areas:

1. Design and construction of supercoiled DNA structures that possess desired topology and superheliex density.

Generation of supercoiled structure of DNA in eukaryotic cells is associated with replication, transcription, and packing of DNA into chromatin while in prokaryotic cell, this superstructure can form with the assistance of gyrase and reverse gyrase. Typically, magnitude of superhelical density in both prokaryotic and eukaryotic cells is ca. -0.06 (6% underwinding). Our group is interested in designing and constructing negatively and positively supercoiled DNA that possess superhelical densities between -0.24 and +0.024 and in examining the physical, chemical and biological properties of these DNA topological isomers (Figure A).

2. Development of human topoisomerases inhibitors.

Topoisomerases are the enzymes that release the topological stress of DNA generated by replication and transcription and several other cellular processes and are critical for cell growth and proliferation. It has been demonstrated in the past that human topoisomerase I is the molecular target of several anticancer agents such as the camptothecins, indolocarbazoles and indenoisoquinolines. Since 2005, our research group has been working on (1) design and synthesis of intrinsically curved oligonucleotides of different lengths that contain matched unnatural bases, nicked and gapped sites as well as mismatched base pairs; (2) examination of inhibitory effect of these curved oligonucleotides on the activity of human topoisomerase I and their interating mechanisms; and (3) design and synthesis of oligonucleotide-based human topoisomerase II inhibitors (Figure B).

3. Search for self-cleaving and self-splicing deoxyribosomes

It was uncovered in our lab in 2007 that certain artificially designed non-biologically relevant G-quadruplet could carry out site-specific self-cleavage action. Since then, our research team has been examining the G-quadruplex structures formed by some telometric repeats with the expectation that such G-quadruplexes could perform self-cleaving and self-splicing actions as well (Figure C).

4. Design and synthesis of G-quadruplex-based anticancer drug candidates

G-quadruplexes have been demonstrated by several research groups in the past to be potential targets of anti-cancer drugs. Our research team is interested in developing new reagents that could cause irreversible damage to the tetraplex entity in selective manners.

5. Nutritional and food Chemistry

Our emphasis in these research areas are on investigating the biological activity of polyphenol antioxidants isolated from plant-based food and their anti-aging activity.
Current Projects
  • Carboxyl Graphene-Based Imaging and Detection of Human Histone Acetyltransferase’s Activity in Living Cells and in Cell-Free Systems
  • Cellular imaging, detection, and inhibition of cancer-affiliated human AP endonuclease (APE1)
  • Colon-Specific Release of Short-Chain Fatty Acids from Edible Polysaccharide Gels and Edible Polysaccharide-Coated Capsules
  • Design and Examination of Manipulable Negatively Supercoiled Structures of DNA
  • Design and Synthesis of New Types of Oligonucleotides as Human Topoisomerase Inhibitors
  • Detection, Imaging and Inhibitory Studies of Poly(A)-Specific Ribonuclease in Acute Myeloid Leukemia Cells
  • Detection, Imaging and Inhibitory Studies of Poly(A)-Specific Ribonuclease in Acute Myeloid Leukemia Cells
  • Develop Platinum Complexes as Synergetic Drugs via Targeting Guanine Quadruplex
  • Develop facial bioconjugate methods for specific detection of 5-hydroxymethyl-cytosine in brain tumors
  • Development of Cutting-Edge DNA Nanogels for Pharmaceutical and Medical Applications
  • Examination on Disintegration of Non-B DNA Structures by DNA Helicase-Affiliated Positive DNA Supercoils from Theoretical and Experimental Perspectives
  • Exploration of using novel structures of oligonucleotides as inhibitors and molecular probes for human topoisomerase II?
  • Interfering Activity of human topoisomerase I using intrinsically curved oligonucleotides
  • Nanostructure- and Fluorophore-Based Platforms for Inhibitor-Screening and Detection of Human DNA Ligase I
  • Synthetic Water Channel-Based Biomimetic Hybrid Membranes For Water Desalination
  • Systematic Studies Of DNA Repair Enzyme-Based CancerDiagnosis, Cellular Imaging And Drug Discovery
Selected Publications
  • Xinming Li , Magdeline Tao Tao Ng , Yifan Wang, Tianyan Zhou, Sock Teng Chua, Weixing Yuan, Tianhu Li. (2008). Site-specific self-cleavage of G-quadruplexes formed by human telemetric repeats. Bioorganic & Medicinal Chemistry Letters, .
  • Yifan Wang, Magdeline Tao Tao Ng, Tianyan Zhou, Xinming Li, Choon Hong Tan, Tianhu Li. (2008). C3-Spacer-containing circular oligonucleotides as inhibitors of human. Bioorganic & Medicinal Chemistry Letters, 18, 3597?3602.
  • Xiaoqian Liu, Xinming Li, Tianyan Zhou, Yifan Wang, Magdeline Tao Tao Ng, Wei Xu and Tianhu Li. (2008). Site specific self-cleavage of certain assemblies of G-quadruplex. J. Chem. Soc., Chem. Commun., , 380 - 382.
  • Yifan Wang, Xinming Li, Xiaoqian Liu and Tianhu Li. (2007). An i-motif-containing DNA device that breaks certain forms of Watson–Crick interactions. J. Chem. Soc., Chem. Commun., , 4369 - 4371.
  • Li, Xinming; Ng, Magdeline Tao Tao; Wang, Yifan; Liu, Xiaoqian; Li, Tianhu. (2007). Dumbbell-shaped circular oligonucleotides as inhibitors of human topoisomerase I. Bioorganic & Medicinal Chemistry Letters, 17(17), 4967-4971.

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