University of California, San Diego | Skaggs School of Pharmacy and Pharmaceutical Sciences
PROTEASE RESEARCH
Proteases for Production of Active Peptides in Neurotransmission, Hormone Action,and Neurodegenerative Diseases
The focus of research in the Hook Laboratory is to understand how proteases and protease inhibitors generate active peptide neurotransmitters and hormones (neuropeptides) for cell-cell communication in the nervous and endocrine systems, and how proteases generate toxic peptides in neurological diseases.
(more)
RESOURCES: BIOCHEMISTRY, MOLECULAR AND CELL BIOLOGY, GENETICS, AND PROTEOMICS
Protease Pathways
IPS, MEROPS Database,
Kegg, Mimi
Mass Spectrometry
Instruments, Analysis, HUPO
PROTEOMICS
Proteomics and Mass Spectrometry in Biomedical Research for Translation into Clinical Therapeutics
In the post-genomic era, it is now critical to understand the function of the gene products in studies of protein function and differential expression profiling of proteins and peptides. We are using several approaches in protein separation techniques, with quantitative labeling by fluorescent or isotopic reagents, for evaluation of proteomes and differential protein expression profiling. We are conducting a proteome study of secretory vesicles, to understand the protein components that provide for functional secretory vesicle function. This work is complemented with human protease gene bioinformatics and arrays to examine proteases within this organelle. In addition, neuropeptidomics to investigate profiles of active peptide neurotransmitters is being studied combined with peptide markers for applications to disease and drug therapeutic conditions. Proteomics will have impact in future clinical research to define new drug targets and therapeutics.
(more)Recent Publications:
Hook, V., Hwang, S.R., Wegrzyn, J., and Bark, S. (2009) Neuropeptides: chemical activity profiling and proteomic approaches. Wiley Encyclopedia of Chemical Biology, pp. 1-12.
Lu, W.D., Asmus, K., Hwang, S.R., Li, S., Woods, V.L., and Hook, V. (2009) Differential accessibilities of dibasic prohormone processing sites of proenkephalin to the aqueous environment revealed by H-D exchange mass spectrometry. Biochemistry 48, 1604-1612.
Bark, S.J., Lu, W.D., and Hook V. (2009) Linear and accurate quantitation of proenkephalin-derived peptides by isotopic labeling with internal standards and mass spectrometry.Anal. Biochem. 389, 18-26.
Highlighted Publications:
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. Toxicol. 48, 393-423.
Funkelstein, L., Toneff, T., Hwang, S.R., Beuschlein, F., Lichtenauer, U.D., Reinheckel, T., Peters, C., and Hook, V. (2008) Major role of cathepsin L for producing the peptide hormones ACTH, β- endorphin, and α-MSH, illustrated by protease gene knockout and expression. J. Biol. Chem. 83, 35652-35659.