Janet S. Lee, MD
Professor of Medicine
Dr. Lee is Professor of Medicine, University of Pittsburgh School of Medicine.
UPMC Montefiore Hospital - NW628
3459 Fifth Avenue
Pittsburgh, PA 15213
Office Telephone: 412-692-2210
- BA - 1991, The Johns Hopkins University
- MD - 1995, Georgetown University School of Medicine
Dr. Lee's clinical interest and focus is acute lung injury, acute and chronic respiratory failure, transfusion consequences in the critically ill, prolonged critical illness and sepsis-induced immunosuppression. Her clinical service is primarily focused in the Medical Intensive Care Unit and the Advanced Lung Disease Service of the University Hospital. She is actively involved in research training and teaching of medical students, graduate students, residents and fellows in Pulmonary and Critical Care Medicine.
Broadly speaking, our laboratory studies host susceptibility to lung injury and the role of phagocytes that orchestrate and participate in the injury response as well as aid in the repair and resolution of inflammation. We utilize a repertoire of relevant injury models including bacterial pneumonia, sterile LPS-induced lung injury, chronic cigarette smoke exposure and RBC transfusion to study innate immune activation signals triggered during lung inflammation and subsequent de-activation signals requisite for appropriate resolution.
One focus of our laboratory is how macrophages respond to damaged cells and the triggering of anti-inflammatory cytokine production involved in the resolution process following lung injury. When this process is disrupted, the host is unable to adequately orchestrate de-activation signals and there is persistence of inflammation and injury. When there is too much, there is immunosuppression. RBC transfusion is an independent risk factor for the development of acute respiratory distress syndrome in at risk populations. Our group aims to understand how macrophages respond to constituents of RBC transfusates that include aged, damaged red cells, membrane-derived microparticles and hemoglobin breakdown products.
Another focus of our laboratory is mechanisms underlying persistent neutrophilic lung inflammation. We are currently interested in thrombospondin-1 (TSP-1), a multifunctional extracellular matrix glycoprotein, involved in cell-cell and cell-matrix interactions and released during inflammation. TSP-1 is protective during lung injury and aids in the resolution of sterile inflammation by facilitating the production of the anti-inflammatory cytokine IL-10 by macrophages. However, during chronic neutrophilic lung inflammation such as in bronchiectasis and COPD, excessive TSP-1 expression from persistent platelet and neutrophil activation may paradoxically contribute to impaired microbial killing, leading to a vicious cycle of inflammation and tissue destruction.
- Zhao Y, Xiong Z, Lechner EJ, Chan Y, Zhang Y, Ross MA, Stolz DB, Rosengart MR, Pilewski J, Ray P, Ray A, Silverstein RL, Lee JS. Thrombospondin-1 triggers macrophage IL-10 production and promotes resolution of experimental lung injury. Mucosal Immunol. 2013 Sept. 18 doi: 10.10381/mi. 2013.63. PMID 24045574
- Xiong Z, Oriss TB, Rosengart MR, Lee JS. Red Cell Microparticle Enumeration: Validation Using a Flow Cytometric Approach. Vox Sanguinis. Vox Sang. 2012 Jan 11. doi: 10.1111/j.1423-0410.2011.01577.x. [Epub ahead of print] PMID 22236393.
- Lee JS, Sperry JL, Vodovotz Y, Rosengart MR. Persistence of elevated CXCL8 concentrations following red cell transfusion in a trauma cohort. Shock. 2012 Apr;37(4):373-7. PMID 22293598 PMCID: PMC3346279
- Zhao Y, Mangalmurti N, Xiong Z, Prakash B, Guo F, Stolz DB, Lee JS. Duffy antigen mediates chemokine endocytosis through a macropinocytosis-like process in endothelial cells. Plos One. 2011;6(12):e29624. Epub 2011 Dec 27. PMID 22216333 PMCID: PMC3246497
- Woodske M, Donahoe M, Yazer M. Lee JS. Acute exacerbation of subclinical pulmonary fibrosis following red cell transfusion: a case report. Transfusion. 2011 Aug 9. doi: 10.1111/j.1537-2995.2011.03296.x. [Epub ahead of print]; PMID 21827507 PMCID: PMC3214228
- Xiong Z, Leme AS, Ray P, Shapiro SD, Lee JS. CX3CR1+ Lung Mononuclear Phagocytes Spatially Confined to the Interstitium Produce TNF-a and IL-6 and Promote Cigarette Smoke Induced-Emphysema. J Immunol. 2011 Mar 1;186(5):3206-14. Epub 2011 Jan 28. PMID: 21278339
- Mei J, Liu Y, Dai N, Favara M, Greene T, Jeyaseelan S, Poncz M, Lee JS, Worthen GS. CXCL5 regulates chemokine scavenging and pulmonary host defense to bacterial infection. Immunity. 2010 Jul 23;33(1):106-117. PMID: 20643340 (with accompanying editorial)
- Mangalmurti NS, Chatterjee S, Chen GJ, Mohammed A, Anderson E, Siegel DL, Schmidt AM, Albelda SM, Lee JS. Advanced glycation endproducts on stored erythrocytes increase endothelial reactive oxygen species generation through interaction with RAGE. Transfusion. 2010 May 13. [Epub ahead of print]. PMID: 20492604
- Lee JS, Gladwin MT. Bad Blood: The Risks of Red Cell Storage. Bedside to Bench Invited Commentary. Nature Medicine 2010 Apr;16(4):381-2. PMID: 20376046
- Mangalmurti NS, Xiong Z, Hulver M, Ranganathan M, Liu XH, Oriss T, Rubin M, Triulzi D, Choi A, Lee JS. Loss of Red cell Chemokine Scavenging Promotes Transfusion Related Lung Inflammation. Blood 2009 Jan 29;113(5):1158-66.PMID: 19064726, PCMID: PMC2635081.