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Genetics,
Structure and Function of Mast Cell Secretory Proteases 
My lab explores roles of mast cells. Focusing on proteases secreted by
mast cells, we characterized their major secreted proteins, tryptases
and chymases. Achievements include first cloning of a tryptase and human
chymase and discovery of new functions of these enzymes as peptidases,
secretagogues, mitogens and modulators of smooth muscle tone. We identified
potent tryptase inhibitors and helped launch pharmaceutical development
of tryptase inhibitors for asthma. We discovered new tryptases and identified
polymorphisms and human deficiency states. Our studies of chymases involve
crystallization, modeling and establishment of structure-activity relationships,
particularly relating to cleavage of angiotensin I to generate vasoactive
angiotensin II. Recently we characterized a mouse deficient in chymase
activity, allowing us to probe roles of this class of enzyme in host defense
and homeostasis. We are also testing new mouse models of selective mast
cell deficiency. Increasingly, our work suggests ways in which mast cells
influence wound healing, tissue remodeling, fibrosis, tumorigenesis, and
innate immune responses, which differ from the allergic phenomena with
which mast cells are traditionally linked. These studies are helping to
redefine the mast cell1s role in biology.
Selected Publications:
Coussens LM, Raymond WW, Bergers G, Behrendtsen O, Werb Z, Caughey GH,
Hanahan D. Inflammatory mast cells potentiate the angiogenic switch during
squamous epithelial carcinogenesis. Genes & Development 13:1382-1397,
1999.
Caughey GH, Raymond WW, Blount JL. Hau LW-T, Pallaoro M, Wolters PJ, Verghese
GM. Characterization of human g-tryptases, novel members of the chromosome
16p mast cell tryptase and prostasin gene families. J Immunol 164:6566-6575,
2000.
Wolters PJ, Muilenburg D, Pham CTN, Ley TJ, Caughey GH. Dipeptidylpeptidase
I is essential for in vivo activation of mast cell chymases, but not tryptases.
J Biol Chem 276:18551-18556, 2001.
Contact Information:
Email: ghc@itsa.ucsf.edu
Phone: 415/ 476-9920
Address: Box 0911, Room SU 206
The University of California, San Francisco, CA 94143, (415) 476-9000
Copyright 2003, The Regents of the University of California.
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