University of California, San Diego | Skaggs School of Pharmacy and Pharmaceutical Sciences

PROTEASE RESEARCH

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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.

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RESOURCES: BIOCHEMISTRY, MOLECULAR AND CELL BIOLOGY, GENETICS, AND PROTEOMICS

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.

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Recent Publications:

Funkelstein L, Beinfeld M, Minokadeh A, Zadina J, Hook V. (2010) Unique biological function of cathepsin L in secretory vesicles for biosynthesis of neuropeptides. Neuropeptides 44, 457-66.

 

Hook V, Bark S, Gupta N, Lortie M, Lu WD, Bandeira N, Funkelstein L, Wegrzyn J, O'Connor DT, Pevzner P. (2010) Neuropeptidomic components generated by proteomic functions in secretory vesicles for cell-cell communication. AAPS J. 12, 635-45.

 

Gupta N, Bark SJ, Lu WD, Taupenot L, O'Connor DT, Pevzner P, Hook V. (2010) Mass spectrometry-based neuropeptidomics of secretory vesicles from human adrenal medullary pheochromocytoma reveals novel peptide products of prohormone processing. J Proteome Res. 9, 5065-75.

 

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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. Tox. 48, 393-423.

 

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.


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