Dr. Liu is also a professor of chemistry and chemical biology at Harvard University and a senior associate member of the Broad Institute of Harvard and the Massachusetts Institute of Technology.
Next-Generation Macromolecular and Small-Molecule Tools for the Understanding and Treatment of Disease
David Liu's research integrates chemistry and evolution to illuminate and program biology, especially toward the development of new therapeutics. His major research interests include (1) the discovery of therapeutically relevant synthetic molecules using DNA-templated synthesis, a technique developed in his laboratory, and Darwinian selection; (2) the characterization and engineering of genome-editing proteins toward next-generation human therapeutics; and (3) the laboratory evolution and delivery in vivo of proteins that catalyze the covalent modification of genes and gene products in human cells.
The skills of human biochemists pale compared with those in nature; evolution has created more efficient, selective, and sensitive ways to synthesize molecules. Harnessing natures synthetic ingenuity could yield important insights into chemistry and biology.
David Liu uses the natural tendency of nucleotides to selectively attach to one another to guide the synthesis of complex molecules. Nucleotides on one strand of DNA zip together with those on another, adenines pairing with thymines and guanines with cytosines. Liu uses this complementarity to guide chemical synthesis by attaching precursors of desired molecules to DNA strands containing specific nucleotide sequences. Natural pairing of their associated DNA strands causes the precursors to undergo chemical reactions that form a desired molecule.
He found DNA-templated organic synthesis to be surprisingly general, able to direct a range of chemical reactions even if the structures of the reactants or products do not resemble the natural DNA backbone that supports the nucleotides.
Liu developed strategies to use DNA-templated synthesis in the multistep creation of a range of complex organic small molecules and organic polymers. Such strategies allow the controlled synthesis of molecules through reaction pathways that would not be possible by traditional methods. His techniques have been used to generate diverse libraries of small molecules in a single solution.
Liu is developing ways to quickly synthesize and select from large libraries of molecules those with desired properties, to synthesize new types of polymers, and to discover new chemical-bond-forming reactions. He is using related techniques to evolve functional biological macromolecules, such as proteins and RNAs, to probe the mechanisms of biological systems.