Patty J Lee, MD

Professor; Interim Section Chief (1/1/10 - 6/30/12); Director of Research (Pulmonary)

Research Interests

Endothelium; Endothelium, Vascular; Pulmonary Medicine; Toll-Like Receptors; Heme Oxygenase-1; Lung Injury

Research Organizations

Internal Medicine: Patty Lee Lab | Pulmonary, Critical Care & Sleep Medicine: CPIRT - Pulmonary Infection Research and Treatment

Faculty Research

Radiobiology & Radiotherapy

Vascular Biology and Therapeutics Program

Yale Center for Research on Aging (Y-Age)

Office of Cooperative Research

Research Summary

Dr. Lee's laboratory studies the mechanisms whereby the lung responds to and protects against oxidant injury. Oxidant injury is caused by excessive reactive oxygen species and is an important component of processes such as acute respiratory failure, inhaled oxygen therapy, lung transplantation and chronic obstructive lung disease. We have identified important molecules, such as heat shock proteins, and more recently, innate immunity receptors that function to protect the lungs against oxidant challenges. We have also developed techniques to silence specific genes in the lung and endothelial cells in vivo, which allows us to ascertain gene function in a highly specific manner.

Specialized Terms: Oxidant-induced acute and chronic lung injury; Toll-like receptors in lung and endothelium; Lung-targeted RNA interference; Heme oxygenase-1 in lung and vascular injury

Extensive Research Description

My laboratory investigates mechanisms of lung injury and cytoprotection during oxidant stress. Specifically, we have focused on the lung endothelium as a central mediator of lung injury and repair responses. We identified the importance of the stress-response protein heme oxygenase-1 (HO-1) and its gaseous reaction product, carbon monoxide (CO), in resisting oxidant-induced endothelial cell death via mitochondrial pathways. We found that a family of signaling molecules, mitogen-activated protein kinases (MAPKs), mediates HO-1 and CO’s protective effects as well as optimal IL-13-induced lung inflammation / remodeling and, more recently, critical innate immune responses. The innate immune system consists of pattern-recognition receptors called toll-like receptors (TLRs), of which TLR4 is the LPS-responsive receptor. We discovered that TLR4 is required for lung structural cell survival in aging and oxidant-challenged conditions. These studies represent important paradigm shifts in our understanding of TLR and lung biology and are now the basis of translational studies in people with acute lung injury and age-related chronic lung disease, such as chronic obstructive lung disease. In the process of our investigations, we were the first to demonstrate the utility of intranasal, lung-targeted and endothelial-targeted silencing RNA (siRNA) constructs in vivo. In parallel, we have also generated endothelial-targeted transgenic and knockout mouse models to specifically interrogate the role of the endothelium in lung disease. Our coordinated use of siRNA technology and genetic approaches in both cell and mouse models offer immense insight into disease pathogenesis and may identify novel therapeutic targets for a range of lung diseases.

  1. Role of the innate immune system in oxidant lung injury
  2. Role of the innate immune system in chronic obstructive lung disease
  3. Heme oxygenase-1 in oxidant lung and vascular injury
  4. Role of aging in lung injury and repair
  5. Role of the lung endothelial cell in lung injury and repair

Selected Publications

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Contact Info

Patty J Lee, MD
Patient Care Location
Yale Pulmonary & Critical Care MedicineYale New Haven Hospital
20 York Street

New Haven, CT 06510
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Lab Location
The Anlyan Center
300 Cedar Street, Ste South 430

New Haven, CT 06519
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Mailing Address
PO Box 208057
300 Cedar Street

New Haven, CT 06520-8057

The Patty J. Lee Laboratory