Marc Peters-Golden, M.D.
Professor, Department of Internal Medicine
Division of Pulmonary and Critical Care Medicine

petersm@umich.edu


Research Interests:

My research centers on the expression, regulation, and biological roles of cellular arachidonic acid metabolism to eicosanoids (prostaglandins and leukotrienes) in health and disease. This includes studies examining:

1. Expression of the enzymes involved in eicosanoid synthesis (i.e., phospholipase A2, 5-lipoxygenase [5-LO], cyclooxygenase [COX], and 5-LO activating protein) and how this is influenced by anatomic site (e.g., lung specificity) and by substances such as cytokines and leptin

2. Intracellular trafficking of eicosanoid-forming enzymes, especially 5-LO, into the nucleus and to membranes, and the role of subcellular localization in protein function

3. Expression and signaling through the major G protein-coupled receptors for leukotrienes and prostaglandin E2 (PGE2)

4. The role of abnormalities in eicosanoid production and responsiveness in the pathogenesis of pulmonary fibrosis. In particular, we have demonstrated that patients with this condition overproduce pro-fibrotic leukotrienes and underproduce anti-fibrotic PGE2, and studies using transgenic animals mimicking these eicosanoid abnormalities in models of pulmonary fibrosis, as well as cellular studies of enzyme and receptor expression, are underway.

5. The role of eicosanoids in innate immunity. We have shown that leukotrienes are necessary for pulmonary antimicrobial defense and phagocyte function, and that patients with HIV infection have impaired leukotriene generation. By contrast, PGE2 suppresses phagocyte function. Ongoing studies are examining the in vivo role of eicosanoids in lung microbial clearance, the mechanisms by which they act, and the therapeutic utility of targeting eicosanoids to stimulate innate immune responses in the lung.

6. Novel signaling mechanisms mediating effects of eicosanoids. We are exploring the roles of the lipid phosphatase PTEN and the cyclic AMP acceptor Epac in mediating the modulatory actions of eicosanoids on inflammatory cell function.

Representative publications:

1.  Aronoff DM, Canetti C, Serezani CH, Luo M, Peters-Golden M. Cutting edge: macrophage inhibition by cAMP: differential roles of protein kinase A and exchange protein activated by cAMP-1. J Immunol 2005; 174:595-599.

2. Peters-Golden M, Canetti C, Mancuso P, Coffey MJ. Leukotrienes: underappreciated mediators of innate immune responses. J Immunol 2005; 173:589-594.

3. Benjamim C, Canetti C, Cunha FQ, Kunkel SL, Peters-Golden M. Opposing and hierarchical roles of leukotrienes in innate immune and vascular responses in a model of sepsis. J Immunol 2005; 174:1616-1620.

4. Serezani CH, Aronoff DM, Jancar S, Mancuso P, Peters-Golden M. Leukotrienes enhance the bactericidal activity of alveolar macrophages against Klebsiella pneumoniae through the activation of NADPH oxidase. Blood 2005; 106:1067-1075.

5. Serezani CH, Aronoff DM, Jancar S, Peters-Golden M. Leukotriene B4 mediates p47phox phosphorylation and membrane translocation in polyunsaturated fatty acid-stimulated neutrophils. J Leukoc Biol 2005; 78:976-984.

6. Peres CM, Aronoff DM, Serezani CH, Flamand N, Faccioli LH, Peters-Golden M. Specific leukotriene receptors couple to distinct G proteins to effect stimulation of alveolar macrophage host defense functions. J Immunol 2007; 179:5454-61.

7. Serezani CH, Chung J, Ballinger MN , Moore BB, Aronoff DM, Peters-Golden M. Prostaglandin E2 suppresses bacterial killing in alveolar macrophages by E prostanoid receptor 2/4-mediated inhibition of NADPH oxidase activation. Am J Respir Cell Mol Biol 2007; 37:562-70.

8. Peters-Golden M, Henderson WR, Jr. Leukotrienes. N Engl J Med 2007; 357:1841-1854.

9. Canetti C, Serezani CH, Atrasz RG, White ES, Aronoff DM, Peters-Golden M. Activation of phosphatase and tensin homologue on chromosome ten ( PTEN ) mediates the inhibition of Fc g receptor phagocytosis by prostaglandin E2 in alveolar macrophages. J Immunol 2007; 179:8350-6.

10. 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; 39:127-32.