Professor, Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine
My research focuses on the cellular and molecular biology of inflammation, innate immunity, and fibrotic responses to tissue injury, particularly in the lung. We have longstanding interest and expertise in the expression, regulation, and biological roles of eicosanoid lipid mediators (particularly prostaglandins and leukotrienes) in health and disease, and some of our work utilizes lipid mediators as a lens through which we view cellular processes. Although the questions we ask require that we study a variety of cell types, the alveolar macrophage and lung fibroblast are our “favorites.” Current interests and projects include:
- Macrophage biology and its regulation by eicosanoids. Current projects include: a) the regulation of pattern recognition receptor pathways; b) regulation of macrophage maturation; c) macrophage secretion of proteins via vesicles such as microparticles and exosomes, its biological relevance in vitro and in vivo, and its regulation.
- The role of macrophages and eicosanoids in animal models of allergic asthma.
- The role of abnormalities in eicosanoid production and responsiveness in the pathogenesis of pulmonary fibrosis. Current projects include: a) molecular pathways involved in fibroblast activation that are targets for prostaglandin modulation; b) mechanisms for dysregulated signaling in fibrotic mesenchymal cells.
- 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
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.
Zasłona Z, Okunishi K, Bourdonnay E, Domingo-Gonzalez R, Moore BB, Lukacs NW, Aronoff DM, Peters-Golden M. Prostaglandin E2 suppresses allergic sensitization and lung inflammation by targeting the E prostanoid 2 receptor on T cells. J Allergy Clin Immunol. 2014 Feb; 133(2):379-387.
Penke LRK, Huang SK, White ES, Peters-Golden M. Prostaglandin E2 inhibits ɑ-smooth muscle actin transcription during myofibroblast differentiation via distinct mechanisms of modulation of serum response factor and myocardin-related transcription factor-A. J Biol Chem. 2014 Jun;289(24):17151-17162