Professor of Internal Medicine,
Chief, Pulmonary & Critical Care Medicine Section
VA Ann Arbor HealthcareSystem
The Curtis lab studies the regulation of pulmonary immunity by lung leukocytes. As a practicing physician involved in multiple clinical studies, the PI has direct access to unique human samples and clinical data. While we use a wide variety of experimental techniques, our forte is advanced flow cytometry, made possible by our own modified LSR II flow cytometer. We also collaborate with a number of other PIBS labs, especially on murine projects and for analysis of the lung microbiome. We welcome graduate students interested in rotations.
Active projects include:
- Immunopathogenesis of chronic obstructive pulmonary disease (COPD), through analysis of leukocytes from human lung tissue, bronchoalveolar lavage and peripheral blood. COPD is a complex group of lung disorders resulting from oxidative damage by smoking or, especially in the developing world, from indoor air pollution. It is currently the third-leading cause of death in the USA, and is projected by the World Health Organization (WHO) to be THE leading cause of death worldwide by 2050. Immune mechanisms appear to be central, but are only beginning to be defined.
- Molecular mechanisms and consequences of apoptotic cell ingestion by murine & human alveolar macrophages. In healthy individuals, billions of cells die by apoptosis each day. Clearance of these apoptotic cells, termed “efferocytosis,” must be efficient to prevent secondary necrosis and the release of proinflammatory cell contents that disrupt homeostasis and potentially foster autoimmunity. During inflammation, most apoptotic cells are cleared by macrophages; the efferocytic process actively induces a macrophage phenotype that favors tissue repair and suppression of inflammation. Chronic lung diseases such as COPD, asthma, and cystic fibrosis are characterized by an increased lung burden of uningested apoptotic cells.
- Interactions of lung leukocytes with the lung microbiome. The lower respiratory tracts are not sterile in healthy individuals as previously believed, but instead appear to harbor very small numbers (relative to other bodily surfaces) of bacteria, viruses and fungi. In collaboration with other UM labs, all members of the Lung HIV Microbiome Project, we seek to define the interactions between host immunity and microbes, and among the various microbes themselves, that maintain health or contribute to disease progression.
Dickson RP, Erb-Downward JR, Prescott HC, Martinez FJ, Curtis JL, Lama VN, Huffnagle GB. Cell-associated bacteria in the human lung microbiome. Microbiome (in press).
Freeman CM, Stolberg VR, Crudgington S, Martinez FJ, Han MK, Chensue SW, Arenberg DA, Meldrum CA, McCloskey L, Curtis JL. Human CD56+ cytotoxic lung NK/NKT cells kill autologous lung cells in chronic obstructive pulmonary disease. PLoS One (in press).
Freeman CM, McCubbrey AL, Crudgington S, Nelson J, Martinez FJ, Han ML, Washko GR, Jr, Chensue SW, Arenberg DA, Meldrum CA, McCloskey L, Curtis JL. Basal gene expression by lung CD4+ T cells in chronic obstructive pulmonary disease identifies independent molecular correlates of airflow obstruction and emphysema extent. PLoS One 9; e96421, 2014. doi:10.1371/journal.pone.0096421. PMID: 24805101.
McCubbrey AL, Curtis JL. Efferocytosis and lung disease. CHEST 143:1750-7, 2013. PMID: 23732585. PMCID: PMC3673667.
Freeman CM, Martinez FJ, Han MK, Washko GR Jr., McCubbrey AL, Chensue SW, Arenberg DA, Meldrum CA, Thompson DL, McCloskey L, Curtis JL. Lung CD8+ T cells in COPD have increased expression of bacterial TLRs. Respir Res 2013; 14:13.
McCubbrey AL, Sonstein J, Ames TM, Freeman CM, Curtis JL. Glucocorticoids relieve collectin-driven suppression of apoptotic cell uptake in murine alveolar macrophages through downregulation of SIRPa. J Immunol 2012; 189:112-9.
Erb-Downward JR, Thompson DL, Han MK, Freeman CM, McCloskey L, Young VB, Toews GB, Curtis JL, Sundaram B, Martinez FJ, Huffnagle GB. Analysis of the lung microbiome in the “healthy” smoker and in COPD. PLoS One 2011; 6:e16384.
Freeman CM, Han M-LK, Martinez FJ, Murray S, Liu LX, Chensue SW, Polak T, Sonstein J, Todt JC, Ames TM, Arenberg DA, Meldrum CA, Getty C, McCloskey L, Curtis JL. Cytotoxic potential of lung CD8+ T cells in COPD is increased with disease severity and by in vitro stimulation with IL-18 and IL-15. J Immunol 2010;184:6504-13.
Phipps JC, Aronoff DM, Curtis JL, Goel D, Mancuso P. Cigarette smoke exposure impairs pulmonary bacterial clearance and alveolar macrophage complement-mediated phagocytosis of S. pneumoniae. Infect Immun 2010;78:1214-20.
Freeman CM, Martinez FJ, Han M-LK, Ames TM, Chensue SW, Todt JC, Arenberg DA, Meldrum CA, Getty C, McCloskey L, Curtis JL. Lung dendritic cell expression of maturation molecules increases with worsening COPD. Am J Respir Crit Care Med 2009;180:1179-1188.
Todt JC, Hu B, Curtis JL. The scavenger receptor SR-A I/II (CD204) signals via the receptor tyrosine kinase Mertk during apoptotic cell uptake by murine macrophages. J Leukocyt Biol 2008;84:510-518.
Curtis JL, Freeman CM, Hogg JC. The immunopathogenesis of COPD: insights from recent research. Proc Am Thorac Soc 2007;4:512-21.
Curtis JL. Cell-mediated adaptive immune defense of the lungs. Proc Am Thorac Soc 2005;2:412-416.
Milik AM, Beuchner-Maxwell VA, Kim S, Sonstein J, Seitzman GD, Beals TF, Curtis JL. Lung lymphocyte elimination by apoptosis in the murine response to intratracheal antigen. J Clin Invest 1997;99:1082-91.