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Kevin Kim, MD is Assistant Adjunct Professor of Medicine and Attending Physician on the Pulmonary Consultation Service. He received his undergraduate degree and medical degree from the University of Michigan. He completed his residency in Internal Medicine at the University of Michigan Health System. He then came to UCSF where he completed his fellowship in Pulmonary and Critical Care Medicine. Since 2004, he has conducted research in the Cardiovascular Research Institute in the laboratory of his mentor, Harold A. Chapman, MD.
Pulmonary fibrosis is often a complication of acute and chronic lung injury. The processes that lead to fibrosis are poorly understood and diseases such as Idiopathic Pulmonary Fibrosis are largely refractory to current therapies. My focus has been on achieving a better understanding of the role of alveolar epithelial cells in lung fibrosis using animal models of fibrosis and primary alveolar epithelial cells in culture.
Alveolar epithelial cells proliferate to repopulate denuded basement membrane after lung injury, release factors which regulate matrix remodeling, and activate latent TGFb1, promoting fibroblast proliferation and conversion to activated myofibroblasts. Recent evidence indicates that epithelial cells in some tissues may also exert their own plasticity during tissue repair, taking on fibroblast-like features. This epithelial-mesenchymal transition (EMT) involves epithelial cell deaggregation, detachment from the basement membrane and cytoskeletal rearrangement. These phenotypic changes require alterations in molecular expression, with loss of epithelial-specific proteins and upregulation of mesenchymal markers. EMT has been well established as an important pathway during development and carcinogenesis. Accumulating evidence also supports an important role for EMT during pathologic tissue fibrosis. While the specific mechanisms that regulate EMT remain unclear, we have previously demonstrated an important role for the extracellular matrix in regulating of EMT by alveolar epithelial cells. Integrins are the major receptors for extracellular matrix proteins. In addition to their function in cell adhesion, integrins can initiate intracellular signaling or influence signaling through other receptors. Thus, the extracellular matrix microenvironment of the alveolar epithelial cells after lung injury may regulate EMT via integrin signaling. The focus of my current research is to understand how EMT is regulated during pulmonary fibrosis and to understand the function of integrin signaling in regulating EMT.
Kim KK, Kugler MC, Wolters PJ, Robillard L, Galvez MG, Brumwell AN, Sheppard D, Chapman HA. 2006. Alveolar epithelial mesenchymal transition develops in vivo during pulmonary fibrosis and is regulated by the extracellular matrix. Proceedings of the National Academy of Sciences. 103:13180-13185
Wei Y, Czekay R-P, Robillard L, Kugler MC, Zhang F, Kim KK, Xiong J-p, Humphries MJ, Chapman HA. 2005. Regulation of α5β1 integrin by conformation and function by urokinase receptor binding. Journal of Cell Biology. 168:501-511
Grabovac MT, Kim KK, Quinn TE, Hernandez R, Daniel BM. Respiratory care. In: Miller RD (ed). Anesthesia, 6th ed. Philadelphia: Churchill Livingstone, 2005.
Kim KK, Flaherty KR, Long Q, Noboru H, Sisson TH, Colby TV, Travis WD, Martinez FJ, Murray S, Simon RH. 2003. A Plasminogen Activator Inhibitor-1 Promoter Polymorphism and Idiopathic Interstitial Pneumonia. Molecular Medicine. 9:52-56.
Chung S-H, Song W-J, Kim K, Bednarski JJ, Prestwich GD, Holz RW. 1998. The C2 Domains of Rabphilin3A Specifically Bind Phosphatidylinositol 4,5-Bisphosphate Containing Vesicles in a Ca2+-dependent Manner. Journal of Biological Chemistry. 273:10240-10248.
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