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

2. Coffey MJ, Serezani CH, Phare SM, Flamand N, Peters-Golden M. NADPH oxidase deficiency results in reduced alveolar macrophage 5-lipoxygenase expression and decreased leukotriene synthesis. Journal of Leukocyte Biology 2007; 82:1585-1591.

3. 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: 15:179(8):5454-61.

4. Huang SK, Wettlaufer SH, Hogaboam C, Flaherty KR, Martinez FJ, Myers JL, Colby TV, Travis WD, Toews GB, Peters-Golden M. Variable resistance to prostaglandin E2 suppression in lung fibroblasts from patients with usual interstitial pneumonia. Am J Respir Crit Care Med 2008; 177:66-74.

5. 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.

6. White KE, Ding Q, Moore BB, Peters-Golden M, Ware LB, Matthay MA, OlmanMA. Prostaglandin E2 mediates IL-1beta-related fibroblast mitogenic effects in acute lung injury through differential utilization of prostanoid receptors. J Immunol. 2008; 180(1):637-46.

7. Huang SK, Wettlaufer SH, Hogaboam CM, Flaherty KR, Martinez FJ, Myers JL, Colby TV, Travis WD, Toews GB, Peters-Golden M. Variable prostaglandin E2 resistance in fibroblasts from patients with usual interstitial pneumonia. Am J Respir Crit Care Med. 2008; 177(1):66-74.

8. Huang SK, Peters-Golden M. Eicosanoid lipid mediators in fibrotic lung
diseases: ready for prime time? Chest 2008; 133: 1442-50, NIHMSID 76677.

9. Huang SK, Wettlaufer SH, Chung J, Peters-Golden M. Prostaglandin E2 inhibits lung fibroblast proliferation and collagen expression via distinct cAMP effector pathways: differential roles of PKA and Epac-1. Am J Respir Cell Mol Biol 2008; 39:482-9. PMC 2551707.

10. 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.

11. Peters-Golden M. Putting on the brakes: cyclic AMP as a multipronged controller of macrophage activation. Perspective. Sci Signal 2009; 2:pe37.