Patty J. Lee, MD
Year elected: 2007
Current membership category: Active
Associate Professor of MedicineYale University School of Medicine
PO Box 208057
333 Cedar Street
New Haven, CT 06520-8057
United States of America
Phone: (203) 737-4612
Facsimile: (203) 785-5952
My laboratory investigates mechanisms of lung injury and cytoprotection during oxidant stress. We identified the importance of the stress protein HO-1 in cytoresistance of human epithelial cells to oxidant injury and uncovered the ability of HO-1 to respond to wide ranges of ambient oxygen tensions via distinct signaling mechanisms. We have shown that the gaseous product of HO-1 catalysis, CO, can profoundly modulate apoptosis via MAPK-dependent death receptor and mitochondrial apoptosis pathways. Expanding upon our examination of MAPK, we demonstrated ERK1/2 MAPK, rather than the canonicaI STAT6 pathway, as necessary for optimal IL-13-induced lung inflammation and remodeling in vivo, thereby establishing ERK1/2 as a legitimate target for controlling Th-2-mediated processes. More recently, we identified a critical role for TLR4 in lung structural cell survival. TLR4 combats apoptosis during lethal oxidant injury and regulates the basal oxidant milieu of the lung, thus preventing emphysema. These studies represent important paradigm shifts in our understanding of TLR and lung biology. In the process of investigating these mechanisms, we were first to demonstrate the utility of intranasal, lung-targeted siRNA in vivo. Our success in applying lung-targeted siRNA against a variety of targets holds immense therapeutic promise for this novel approach to lung disease.
Yale School of Medicine (Primary)
Harriet Margot Kluger, MD is the representative at this institution.