Hung-Wen (Ben) Liu

h.w.liu@mail.utexas.edu

Professor, Faculty
Professor of Pharmacy George H Hitchings Regents Chair in Drug Design

Research Group

Ben Liu Group

Education

PhD, Columbia University, 1981
BS, Tunghai University, 1974

NIEHS Postdoctoral Fellow, Massachusetts Institute of Technology 1981-84

Awards

A. I. Scott Medal for Excellence in Biological Chemistry Research, 2011

American Chemical Society Division of Biological Chemistry, Repligen Award, 2008
Elected Academician, Academia Sinica, 2008
American Chemical Society Organic Division, Nakanishi Prize, 2007
Japan Society for the Promotion of Science Fellow, 2006
Elected Fellow, American Academy of Microbiology, 2006
Elected Fellow, American Association for the Advancement of Science, 2005
Distinguished McKnight University Professor, University of Minnesota, 1999
National Institute of General Medical Sciences MERIT Award, 1999
American Chemical Society Division of Carbohydrate Chemistry, Horace S. Isbell Award, 1993
NIH Research Career Development Award, 1990
NIEHS Postdoctoral Fellow, Massachusetts Institute of Technology, 1984

Affiliations

Institute for Cellular and Molecular Biology

Bioorganic Chemistry and Chemical Biology

The major thrust of my research lies at the crossroads of chemistry and biology. My group is currently working on three general areas with the focus aimed at the elucidation of the mechanisms of novel enzymatic reactions and the design of methods to control and/or regulate their functions.

Enzyme Mechanism and Inhibitor Design

Using a multi-faceted approach, we study the mechanisms of enzymes involved in diverse biological processes including the formation of bacterial cell wall, biosynthesis of and resistance to antibiotics, metabolism of lipids, and the posttranslational modification of nuclear proteins. A significant effort is devoted to the synthesis of compounds as mechanistic probes or specific inhibitors for these biological catalysts.

Metabolic Pathway Engineering

Through selective disruption and/or substitution of sugar biosynthetic genes in the microorganisms which produce bioactive glycosylated secondary metabolites, we have demonstrated the feasibility of engineering nature's biosynthetic machinery for the production of novel compounds carrying designed sugar appendages. Such a combinatorial biosynthetic approach bears a great promise of finding drugs with new or improved biological activity.

Protein Function Regulation

We have recently initiated a study on poly(ADP-ribose) polymerase, an enzyme that recognizes damaged DNA and turns on the repairing machinery through polyADP-ribosylation of itself and other nuclear proteins. Such a posttranslational modification of proteins is also essential to other crucial cellular events including apoptosis. Overall, most of the biological systems under investigation are target candidates for therapeutic drugs. My group is motivated by the challenge and excitement from understanding these biological transformations and tackling the relevant biomedical problems through chemical approaches.

 

Representative Publications

Kim, H. J.; Ruszczycky, M. W.; Choi, S. H.; Liu, Y.-n.; Liu, H.-w. "An Enzyme-Catalyzed  [4+2] Cycloaddition is a Key Step in the Biosynthesis of Spinosyn A." Nature, 2011, 473,  109-112.

Ruszcycky, M. W.; Choi, S.-h.; Mansoorabadi, S. O.; Liu, H.-w. "Mechanistic Studies of the Radical SAM Enzyme DesII: EPR Characterization of a Radical Intermediate Generated During Its Catalyzed Dehydrogenation of TDP-D-Quinovose." J. Am. Chem.  Soc. 2011, 133, 7292-7295.

Sasaki, E.; Liu, H.-w. "Mechanism of the Biosynthesis of 2-Thiosugar: Evidence for the Formation of an Enzyme-Bound 2-Ketohexose Intermediate in BexX-Catalyzed Reaction." J. Am. Chem. Soc. 2010, 132, 15544-15546.

Tao, Z.; Gao, P.; Liu, H.-w. "Studies of the Expression of Human Poly(ADP-ribose) Polymerase-1 in Saccharomyces cerevisiae and Identification of PARP-1 Substrates by  Yeast Proteome Microarray Screening." Biochemistry, 2009, 48, 11745-11754.

Thibodeaux, C. J.; Melancon, C. E., III.; Liu, H.-w. "Natural Product Sugar Biosynthesis and Enzymatic Glycodiversification." Angew. Chem. Int. Ed. 2008, 47, 9814-9859.

Thibodeaux, C. J.; Melançon, C. E.; Liu, H.-w. "Unusual Sugar Biosynthesis and Natural Product Glycodiversification." Nature 2007, 446, 1008-1016.