Associate Professor of Pathology
Harvard Medical School
NRB-930F
77 Avenue Louis Pasteur
Boston, MA 02115
PH: 617-432-6581
FX: 617-432-6580
WingMing_Keung@hms.harvard.edu

Research Interests

Our laboratory conducts basic and preclinical research on medicinal herbs and biologically active natural products isolated therefrom. Objectives are to strengthen the scientific knowledge bases needed to inform clinical practice involving the use of botanicals in general, and identify active principles as potential leads for new drug discovery and molecular probes for basic, mechanistic, and preclinical research in particular. Our current research focuses on Radix Puerariae and Rhizoma Acori Gramminei, botanicals traditionally used for the treatment of alcohol dependence/abuse and Alzheimer’s disease (AD), respectively.

 Projects

 (1) Understanding the role of monoamine oxidase (MAO)/aldehyde dehydrogenase (ALDH2) pathway in the regulation of alcohol drinking. ALDH2 of the MAO/ALDH2 pathway has been identified as the site of action of daidzin, the active principle of Radix Puerariae.

 (2) Design and synthesis of analogs of daidzin that are more efficacious and with better ADME properties based on the x-ray structure of human ALDH2 in complex with daidzin.

 (3) Evaluating the therapeutic and prophylactic potential of Rhizoma Acori Gramminei and its active principle(s).

 (4) Understanding the biochemical basis underlying the anti-amyloid b activity of Rhizoma Acori Gramminei and its active principle(s).

Publications

1. Rooke N, Li DJ, Li J, Keung WM. The Mitochondrial Monoamine Oxidase - Aldehyde Dehydrogenase Pathway - A Potential Site of Action of Daidzin. J. Med. Chem. 2000; 43(20):4169-4179.

 2. Irie Y, Keung WM. Metallothionein-III antagonizes the neurotoxic and neurotrophic effects of amyloid _ peptides. Biochem. Biophys. Res. Commun. 2001; 282:416-420.

 3. Gao GY, Li D-J, Keung WM. Synthesis of potential antidipsotropic isoflavones: inhibitors of the mitochondrial monoamine oxidase-aldehyde dehydrogenase pathway. J. Med. Chem. 2001; 40:3320-3328.

 4. Keung WM. Biogenic aldehyde(s) derived from the action of monoamine oxidase may mediate the antidipsotropic effect of daidzin. In: Enzymology and Molecular Biology of Carbonyl Metabolism. Eds. Weiner, H., Maser, E., Hurley, T, &
 5. Lindahl, R. Elseview Science B.V., The Netherlands, pp919-930, 2001.

 6. Keung WM. Pueraria: The genus pueraria, Taylor & Francis, London, 2002.

 7. Chen Y, Irie Y, Keung WM, Wolfgang M. S-Nitrosothiols react preferentially with zinc thiolate clusters of metallothionein III through transnitrosation. Biochemistry 2002; 41:8360-8367.

 8. Keung WM. Monoamine oxidase inhibitors. Expert Opinion on Therapeutic Patents 2002; 12:1813-1829.

 9. Irie Y, Keung WM. Anti-amyloid b activity of metallothionein-III is different from its neuronal growth inhibitory activity: structure-activity studies. Brain Research 2003; 960:228-234.

 10. Irie Y, Keung WM. Rhizoma Acori Gramminei and its active principles protect PC-12 cells from the toxic effects of amyloid b peptide. Brain Research 2003; 963:282-289.

 11. Overstreet DH, Keung WM, Rezvani AH, Massi M, Lee DYW. Herbal remedies for alcoholism: promises and pitfalls. Alcohol: Clin. Exp. Res. 2003; 27(2):177-185.

 12. Keung WM. Antidipsotropic Isoflavones: The Potential Therapeutic Agents for Alcohol Dependence. Medicinal Research Reviews 2003; 23(6):669-696.

 13. Gao G-Y, Li D-J, Keung WM. Synthesis of Daidzin Analogues as Potential Agents for Alcohol Abuse. Bioorganic & Medicinal Chemistry 2003; 11:4069-4081.

 14. Irie Y, Itokazu N, Anjiki N, Ishige A, Watanabe K, Keung WM. Eugenol Exhibits Antidepressant-like Activity in Mice and Induces Expression of Metallothionein-III in the Hippocampus. Brain Research 2004; 1011:243-246.

 15. Green AI, Chau DT, Keung WM, Dawson R, Mesholam RI, Schildkraut JJ. Clozapine reduces alcohol drinking in Syrian golden hamsters. Psychiatry Research 2004; 128:9-20.

 16 Irie Y, Mori F, Keung WM, Mizushima Y, Wakabayashi K. Expression of Neuronal Growth Inhibitory Factor (Metallothionein-III) in the Salivary Gland. Physiological Research 2004; 53:719-723.

17 Tao G, Irie Y, Li D-J, Keung WM.  Eugenol and Its structural analogs Inhibit monoamine oxidase A and exhibit antidepressant-like activity. Bioorganic & Medicinal Chemistry 2005; 13:4777-4788.

18 Jornvall H, Shafqat J, Astorga-Wells J, Jonsson A, Norin A, Bergman T, Hirschberg D, Hjelmqvist L, Keung WM.  MDR alcohol dehydrogenases: Novel forms and possibilities. In: Enzymology and Molecular Biology of Carbonyl Metabolism. Eds. Weiner, H., Maser, E., Hurley, T, & Lindahl, R. Elseview Science B.V., The Netherlands, pp1-5, 2005.

19. Kollau A, Hofer A, Russwurm M, Koesling D, Keung WM, Schmidt K, Brunner F, Mayer B. Contribution of aldehyde dehydrogenase to mitochondrial bioactivation of nitroglycerin. Evidence for activation of purified soluble guanylyl cyclase via direct formation of nitric oxide. Biochemical Journal 2005, 385:769-777.