Patty J. Lee, M.D.

Associate Professor

Educational Background

Medical School: Brown University Program in Medicine, Providence, RI
Residency: Internal Medicine, Johns Hopkins School of Medicine, Baltimore, MD
Fellowship: Pulmonary & Critical Care Medicine, Johns Hopkins School of Medicine

Clinical Interests

Acute lung injury, Adult respiratory distress syndrome

Research Interests

• Oxidant-induced lung injury and apoptosis
• Toll-like receptors in lung
• Lung-targeted RNA interference
• Heme oxygenase-1 and carbon monoxide in lung disease

Dr. Lee has a longstanding interest in the mechanisms of lung injury and cytoprotection during oxidant stress. Her studies have defined novel pathways whereby heme oxygenase-1 (HO-1) and its reaction product, carbon monoxide (CO), exert anti-apoptotic effects in the lung. Specifically, the mitogen-activated protein kinases (MAPKs) are central to HO-1 expression as well as the anti-apoptotic effects of CO. These results have changed our entire conceptualization of CO, previously thought to be a toxic waste product with little biologic value. She extended her MAPK studies to Th2-mediated injury and repair responses. Dr. Lee demonstrated that ERK1/2 MAPK, rather than the canonicaI STAT6 pathway, is required for optimal IL-13-induced lung inflammation and remodeling. These studies were the first to identify ERK1/2 MAPK as a legitimate target for controlling Th-2-mediated injury and remodeling in vivo. Recently, Dr. Lee has established a pivotal role for toll-like receptors (TLR) 4 in lung structural cell survival. Not only does TLR4 combat cellular apoptosis during lethal oxidant injury but also regulates the basal oxidant milieu of the lung and thereby prevents cell death and emphysema. These studies represent an important paradigm shift in our understanding of TLR and lung biology. While investigating these mechanisms, her lab was the first to demonstrate the utility of intranasal, lung-targeted short-interfering RNA in vivo. Recently, she has successfully applied lung-targeted siRNA against a variety of targets, which has immense impact on the use of this novel approach as a therapeutic modality for a broad range of lung diseases. These studies have been supported by the NIH (RO1), American Heart Association, and American Lung Association funding.

Representative publications

Zhang X., Shan P., Jiang G., Cohn L., and Lee P.J. Toll-like receptor 4 deficiency causes pulmonary emphysema. J Clin Invest, 116: 3050-3059, 2006.

Qureshi, S.T., Zhang, X., Aberg E., Bousette N., Giaid A., Shan P., Medzhitov, R.M., and Lee P.J. Inducible activation of TLR4 confers resistance to hyperoxia-induced pulmonary apoptosis. J Immunol, 176: 4950-4958, 2006.

Zhang X., Shan P., Jiang G., Zhang S-M., Otterbein L.E., Fu X-Y., and Lee P.J. Endothelial STAT3 is essential for the protective effects of HO-1 in oxidant-induced lung injury. FASEB J, 20: E1528-1538, 2006.

Lee P.J., Zhang X., Shan P., Ma B., Lee CG, Homer RJ, Zhu Z, Rincon M, Mossman BT, and Elias, JA. ERK1/2 mitogen-activated protein kinase selectively mediates IL-13-induced lung inflammation and remodeling in vivo. J Clin Invest, 116: 163-173, 2006.

Zhang X., Shan P., Qureshi S., Homer, R., Medzithov R., Noble P.W., and Lee P.J. Cutting edge: Toll-like receptor 4 deficiency confers susceptibility to lethal oxidant lung injury. J Immunol, 175: 4834-4838, 2005.

Zhang X., Shan P., Alam J., Fu X-Y, and Lee P.J. Carbon monoxide differentially modulates STAT1 and STAT3 and inhibits apoptosis via a phosphatidylinositol 3-kinase/Akt and p38 kinase-dependent STAT3 pathway during anoxia-reoxygenation injury. J Biol Chem, 280: 8714-8721, 2005.

Zhang, X., Shan, P., Jiang, D., Noble, P.W., Abraham, N.G., Kappas, A., and Lee, P.J. Small interfering RNA targeting heme oxygenase-1 enhances ischemia-reperfusion-induced lung apoptosis. J Biol Chem. 279: 10677-10684, 2004.

Zhang X., Shan P., Otterbein L.E., Alam J., Flavell R.A., Davis R.J., Choi A.M.K., and Lee, P.J. Carbon monoxide inhibition of apoptosis during ischemia-reperfusion lung injury is dependent on the p38 mitogen activated protein kinase pathway and involves caspase 3. J Biol Chem. 278:1248-1258, 2003.

Zhang X., Shan P., Alam J., Davis R.J., Flavell R.A., and Lee P.J. Carbon monoxide modulates Fas/Fas Ligand, caspases, and Bcl-2 family proteins via the p38a mitogen activated protein kinase pathway during ischemia-reperfusion lung injury. J Biol Chem. 278: 22061-22070, 2003.

Contact

Campus Address
Department of Internal Medicine
P.O. Box 208057
New Haven, CT 06520-8057

E-mail
patty.lee@yale.edu

Phone
203-785-5877

Fax
203-785-3826