Professor, Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
My research centers on the expression, regulation, and biological roles of eicosanoid lipid mediators (particularly prostaglandins and leukotrienes) in health and disease. This includes studies examining:
1. The role of abnormalities in eicosanoid production and responsiveness in the pathogenesis of pulmonary fibrosis. Approaches include defining abnormalities in cells from diseased patients, using pharmacologic and transgenic strategies to dissect roles of specific eicosanoids or eicosanoid receptors in modulating animal models of fibrosis in vivo, and testing the effects of specific eicosanoids and receptor-triggered signaling cascades on lung fibroblasts. Utilizing this information for therapeutic targeting is also underway.
2. The role of eicosanoids in innate immunity. Ongoing studies are examining the in vivo role of eicosanoids in lung microbial clearance, the mechanisms by which they act (e.g., actions on phagocytosis, TLR signaling, and NADPH oxidase activation), and the therapeutic utility of targeting eicosanoids to stimulate innate immune responses in the lung. New studies are examining the roles of eicosanoids in classical and alternative macrophage polarization.
3. Expression and regulation of enzymes involved in biosynthesis of eicosanoids
4. Signaling through the major G protein-coupled receptors for leukotrienes and prostaglandin E2 (PGE2). In particular, as leukotrienes and PGE2 have opposing effects on the critical intracellular second messenger cyclic AMP, control of cyclic AMP signaling pathways (including activation of protein kinase A and exchange protein activated by cyclic AMP or Epac) is a central topic.
Peters-Golden M, Henderson WR, Jr. Leukotrienes. N Engl J Med 2007;
Serezani CH, Ballinger MN, Aronoff DM, Peters-Golden M. Cyclic AMP: master regulator of innate immune cell function. Am J Respir Cell Mol Biol. 2008; 39(2):127-32.
Medeiros AI, Serezani CH, Lee SP, Peters-Golden M. Efferocytosis impairs pulmonary macrophage and lung antibacterial function via PGE2/EP2 signaling. J Exp Med 2009 206:61-8.
Serezani CH, Aronoff DM, Sitrin RG, Peters-Golden M. FcgammaRI ligation leads to a complex with BLT1 in lipid rafts that enhances rat lung macrophage antimicrobial functions. Blood. 2009;114(15):3316-24.
Mancuso P, Lewis C, Serezani CH, Goel D, Peters-Golden M. Intrapulmonary administration of leukotriene B4 enhances pulmonary host defense against pneumococcal pneumonia. Infect Immun. 2010;78:2264-71.
Bauman KA, Wettlaufer SH, Okunishi K, Vannella KM, Stoolman JS, Huang SK, Courey AJ, White ES, Hogaboam CM, Simon RH, Toews GB, Sisson TH, Moore BB, Peters-Golden M. The antifibrotic effects of plasminogen activation occur via prostaglandin E2 synthesis in humans and mice. J Clin Invest. 2010;120:1950-60
Morato-Marques M, Campos MR, Kane S, Rangel AP, Lewis C, Ballinger MN, Kim SH, Peters-Golden M, Jancar S, Serezani CH. Leukotrienes target F-actin/cofilin-1 to enhance alveolar macrophage anti-fungal activity. J Biol Chem. 2011; 286:28902-13.
Kim SH, Serezani CH, Okunishi K, Zaslona Z, Aronoff DM, Peters-Golden M. Distinct protein kinase A anchoring proteins direct prostaglandin E2 modulation of Toll-like receptor signaling in alveolar macrophages. J Biol Chem. 2011;286:8875-83.
Serezani CH, Lewis C, Jancar S, Peters-Golden M. Leukotriene B4 amplifies NF-κB activation in mouse macrophages by reducing SOCS1 inhibition of MyD88 expression. J Clin Invest. 2011;121:671-82.
Zaslona Z, Serezani CH, Okunishi K, Aronoff DM, Peters-Golden M. Prostaglandin E2 restrains macrophage maturation via E prostanoid receptor 2/protein kinase A signaling. Blood. 2012;119:2358-67.
Serezani CH, Kane S, Medeiros AI, Cornett AM, Kim SH, Marques MM, Lee SP, Lewis C, Bourdonnay E, Ballinger MN, White ES, Peters-Golden M. PTEN directly activates the actin depolymerization factor cofilin-1 during PGE2-mediated inhibition of phagocytosis of fungi. Sci Signal. 2012;5(210):ra12.
Bourdonnay E, Serezani CH, Aronoff DM, Peters-Golden M. Regulation of alveolar macrophage p40phox: hierarchy of activating kinases and their inhibition by PGE2. J Leukoc Biol. 2012;92:219-31.
Serezani CH, Kane S, Collins L, Morato-Marques M, Osterholzer JJ, Peters-Golden M. Macrophage Dectin-1 Expression Is Controlled by Leukotriene B4 via a GM-CSF/PU.1 Axis. J Immunol. 2012;189:906-15.