Kenneth C. Fang, M.D.
Assistant Professor

University of California San Francisco
Surge Rm 206
Box 0911
San Francisco, California 94143
phone: 415-502-7938
fax: 415-476-9749
email: kfang@itsa.ucsf.edu

Dr. Fang received his M.D. degree from the University of Pennsylvania School of Medicine in 1988, and completed a residency in internal medicine and a suspecialty fellowship in pulmonary and critical care medicine at the University of California, San Francisco. Following additional postdoctoral research training in the Cardiovascular Research Institute, he joined the faculty of UCSF in 1996. Dr. Fang’s academic activities include laboratory research, teaching, and attending responsibilities on the pulmonary consultation service, in the intensive care unit, and in the interstitial lung disease clinic.

Research Interests

Fibrogenesis interferes with gas exchange and pulmonary function by causing excessive accumulation of extracellular matrix proteins which distort the architecture of the airways and lung parenchyma. Fibrosis in the lungs remains refractory to therapy and contributes to the insidious and irreversible progression to respiratory failure. Proteolysis plays a role in many tissue remodeling pathways which regulate matrix protein abundance or communications among cells and matrix constituents present in the mesenchyme. Cleavage of a variety of proteins either embedded in matrix or anchored to the cell surface enable proteases of different classes to regulate tissue integrity, molecular signaling, and cellular differentiation and viability during health and disease.

The Fang Lab targets the functions of metalloproteases and their inhibitors, and the specific role of mast cells in regulating metalloproteolytic activity during fibrogenesis. Contributions of the lab include characterization of activation pathways of secreted metalloproteases and mechanisms regulating mast cell expression of metalloproteases. The emphasis on mast cells derives from their puzzling, yet irrefutable abundance in fibrotic tissues, while the focus on metalloproteases builds upon their versatile participation in a variety of processes such as collagen remodeling, apoptosis, angiogenesis, and tumor invasion.

Metalloproteases demonstrate a collective and distinctive ability to cleave all extracellular matrix proteins, which endows them with important roles in many biologic processes requiring tissue breakdown. In addition to their secreted forms, other metalloproteases remain bound to cell membranes where they orchestrate the surface display of proteins such as receptors and growth factors involved in cell communication. As normal residents of the mesenchyme which degranulate and increase in numbers in response to profibrogenic injury, mast cell remain attractive candidates for critical roles in tissue remodeling including the regulation of collagen metabolism and fibroblast behavior.

Fundamental questions remain regarding the function of metalloproteases and tissue inhibitors of metalloproteases in fibrogenesis, the ability of mast cells to regulate local mesenchymal metalloproteolytic activity, and a possible role for metalloproteases in the autoregulation of critical mast cell functions such as differentiation and apoptosis.
An intimate understanding of the clinical challenges of fibrotic lung disorders such as idiopathic pulmonary fibrosis and obliterative bronchiolitis will remain the guide to studying animal and cellular models to identify new molecular targets to achieve the goal of ameliorating, and perhaps reversing, these crippling disorders.

Recent Publications

Frank BT, Rossall JC, Caughey GH and Fang KC. Mast cell tissue inhibitor of metalloproteinase-1 is cleaved and inactivated extracellularly by a-chymase. J Immunology. 2001. 166:2783-2792.

Jonosono M, Fang KC, Keith FM,Turck CW, Blanc PD, Hall TS, Fukano AK, Rifkin CJ, Gold WM, Webb WR, Edinburgh KJ, Finkbeiner W, Golden JA. Measurement of fibroblast proliferation activity in bronchoalveolar lavage fluid in the analysis of bronchiolitis obliterans among lung transplant recipients. J Heart Lung Transplant. 1999; 18:972-985

Fang KC, Wolters PJ, Steinhoff M, Bidgol A, Blount JL, Caughey GH. Mast cell expression of gelatinases A (MMP-2) and B (MMP-9) is regulated by kit ligand and transforming growth factor-b. J. Immunology. 1999, 162: 5528-5535

Caughey, GH, Raymond, WW, Fang KC. Porcine origin of human sputum trypsin? Am J Physiol. 1998.275:L200-L202

Fang KC, Raymond WW, Blount JL, Caughey GH. Dog mast cell a-chymase activates progelatinase B by cleaving the Phe 88-Gln89and Phe91-Glu92 bonds of the catalytic domain. J Biol Chem. 1997. 272:25628-25635

Caughey GH, Blount JL, Koerber K, Kitamura M, Fang KC. Cloning and Expression of the Dog Mast Cell a-Chymase Gene. J Immunology. 1997.159:4367-4375