The Skaggs School of Pharmacy & Pharmaceutical Sciences

Vivian Y. H. Hook

Dr. Vivian Hook received her Ph.D. degree from the University of California, San Francisco in 1980. Prior to coming to UCSD, she conducted neuroscience and pharmacology research with Nobel Laureate Julius Axelrod at the National Institutes of Health, and was Assistant/Associate Professor of Biochemistry and Neurosciences at the Uniformed Services University in Bethesda, MD. She was Professor with the Dept. of Medicine at UCSD for several years and held an appointment with the Buck Institute for Age Research in the San Francisco area. Dr. Hook recently joined the UCSD School of Pharmacy and Pharmaceutical Sciences to bridge biomedical research to disease therapeutics.

Her laboratory investigates protease mechanisms required for production of peptide neurotransmitters and hormones that mediate cell-cell communication. Investigation of selective protease pathways provides knowledge of regulatory components involved in the biosynthesis of beneficial peptides required for normal neuroendocrine functions. This research on neuroproteases extends to those involved in neurodegenerative diseases, including Alzheimer's disease. Interdisciplinary approaches are utilized in enzyme biochemistry, proteomics, and moelcular and cell biology, and genetics. The protease research strives to understand their regulatory roles in producing active peptides in health and disease.

Selected Publications

Yasothornsrikul, S., Greenbaum, D., Medzihradszky, K.F., Toneff, T., Bundey, R., Miller, R., Schilling, B., Petermann, I., Dehnert, J., Logvinova, A., Goldsmith, P., Neveu, J.M., Lane, W.S., Gibson, B., Reinheckel, T., Peters, C., Bogyo, M., and Hook, V. (2003) Cathepsin L in secretory vesicles functions as a prohormone-processing enzyme for production of the enkephalin peptide neurotransmitter. Proc. Natl. Acad. Sci. U S A 100, 9590-9595.

Hook, V., Toneff, T., Bogyo, M., Greenbaum, D., Medzihradszky, K.F., Neveu, J., Lane, W., Hook, G., and Reisine, T. (2005) Inhibition of cathepsin B reduces ?-amyloid production in regulated secretory vesicles of neuronal chromaffin cells: evidence for cathepsin B as a candidate beta-secretase of Alzheimer's disease. Biol. Chem. 386, 931-940.

Hook, V. (2006) Unique neuronal functions of cathepsin L and cathepsin B in secretory vesicles: biosynthesis of peptides in neurotransmission and neurodegenerative disease. Biol. Chem. 387, 1429-1439.

Hwang, S-R., Garza, C., Mosier, C., Toneff, T., Wunderlich, E., Goldsmith, P., and Hook, V. (2007) Cathepsin L expression is directed to secretory vesicles for enkephalin neuropeptide biosynthesis and secretion. J. Biol. Chem. 282, 9556-9563.

Wegrzyn, J., Lee, J., Neveu, J.M., Lane, W.S., and Hook, V. (2007) Proteomics of neuroendocrine secretory vesicles reveal distinct functional systems for biosynthesis and exocytosis of peptide hormones and neurotransmitters. J. Proteome Research 6, 1652-1665.

Bark, S.J. and Hook, V. (2007) The future of proteomic analysis in biological systems and molecular medicine. Molecular BioSystems 3, 14-17.

Hwang, S.-R., O'Neill, A., Bark, S., Foulon, T., and Hook, V. (2007) Secretory vesicle aminopeptidase B related to neuropeptide processing: molecular identification and subcellular localization to enkephalin- and NPY-containing chromaffin granules. J. Neurochem. 100, 1340-1350.

Hook, V., Kindy, M., and Hook, G. (2007) Cysteine protease inhibitors effectively reduce in vivo levels of brain beta-amyloid related to Alzheimer's disease. Biol. Chem. 388, 247-252.

Hook, V., Funkelstein, L., Lu, D., Bark, S., Wegrzyn, J., and Hwang, S.-R. (2008) Proteases for processing proneuropeptides into peptide neurotransmitters and hormones. Annu. Rev. Pharmacol. Tox. 48, 393-423.

Hook, V., Kindy, M., and Hook, G. (2008) Inhibitors of cathepsin B improve memory and reduce Abeta in transgenic Alzheimer's disease mice expressing the wild type, but not the Swedish mutant, beta-secretase APP site. J. Biol. Chem., in press. [Epub ahead print Jan 9 2008]

List of Publications in Pub Med