David Aronoff, M.D.
Assistant Professor
Internal Medicine, Infectious Disease
daronoff@umich.edu

http://sitemaker.umich.edu/aronoff.lab/home


Research Focus:

Host-microbial interactions, with particular areas of interest including innate immunity, macrophage biology, cell signaling, and the regulation of host defense by lipid mediators.


Research Interests:

Female reproductive tract infections and bacterial pneumonia. Particular areas of interest include innate immunity, epithelial cell and macrophage biology, cell signaling, and the regulation of host defense by lipid mediators and G protein coupled receptors.

Current Research Activity:

Our laboratory is interested in the regulation of innate immune system. A primary focus of our work involves the macrophage, which functions as a key sentinel of host defense against invading microorganisms in human tissues. A fundamental question we are trying to answer is the importance of eicosanoids (lipid mediators derived from the cell membrane constituent arachidonic acid) in modulating macrophage antimicrobial functions and host defense. We employ both in vivo animal models of bacterial infection and in vitro cell culture protocols to address this question. Specific areas of investigation include cAMP signaling in the macrophage and mechanisms of regulating three distinct macrophage functions: phagocytosis, intracellular killing, and inflammatory mediator production.

Current models of infection in the Aronoff laboratory include bacterial pneumonia caused by Streptococcus pneumoniae and bacterial endometritis caused by Clostridium sordellii.

Recent Publications:

1. Aronoff DM, Canetti C, Peters-Golden M. Prostaglandin E 2 inhibits alveolar macrophage phagocytosis through an EP2 receptor-mediated increase in intracellular cAMP. J Immunol . 2004; 173: 559-565

2. Aronoff DM, Canetti C, Serezani CH, Luo M, and Peters-Golden M. Cutting Edge: Macrophage inhibition by cAMP: differential roles of protein kinase A and exchange protein directly activated by cAMP-1. J Immunol . 2005; 174 (2): 595-99.

3. White ES, Atrasz RG, Dickie EG, Aronoff DM, Stambolic V, Mak TW, Moore BB, Peters-Golden M. Prostaglandin E 2 inhibits fibroblast migration by EP2 receptor-mediated increase in PTEN activity. Am J Respir Cell Mol Bio. 2005; 32 (2): 135-41 .

4. Serezani CH, Aronoff DM, Jancar S, Mancuso P, and Peters-Golden M. Leukotrienes enhance the bactericidal activity of alveolar macrophages against Klebsiella pneumoniae through the activation of NADPH oxidase. Blood. 2005; 106 (3):1067-75.

5. Young M, Aronoff DM, Engleberg NC. Necrotizing fasciitis: a review of pathogenesis and treatment. Expert Rev Anti Infect Ther . 2005; 3 (2):279-94.

6. Serezani CH, Aronoff DM, Jancar S, and Peters-Golden M. Leukotriene B 4 mediates p47phox phosphorylation and membrane translocation in polyunsaturated fatty acid-stimulated neutrophils. J Leuk Biol . 2005; 78 (4):976-84.

7. Luo M, Jones SM, Flamand N, Aronoff DM, Peters-Golden M, Brock TG. Phosphorylation by protein kinase A inhibits nuclear import of 5-lipoxygenase. J Biol Chem . 2005; 280 (49): 40609-16.

8. Aronoff DM, Mulla ZD. Nonsteroidal Antiinflammatory Drugs and Group A Streptococcal Infection [Letter] . Emerging Infect Dis . 2006; Aug;12(8):1291.

9. Aronoff DM, Oates JA, Boutaud O. New insights into the mechanism of action of acetaminophen: its clinical pharmacology reflects its inhibition of the two prostaglandin H 2 synthases. Clin Pharm Therapeut . 2006; Jan;79(1):9-19. Invited review .

10. Young M, Engleberg NC, Mulla ZD, Aronoff DM. Therapies for necrotising fasciitis. Exp Rev Biol Ther. 2006 Feb;6(2):155-65. Invited review .

11. Ballinger MN, Paine R, Serezani C.H.C., Aronoff DM, Standiford TJ, Toews GB, and Moore BB. Role of GM-CSF during Gram-negative lung infection with Pseudomonas aeruginosa. Am J Respir Cell Mol Biol . 2006; 34(6):766-774.

12. Canetti C, Aronoff DM, Choe M, Flamand N, Wettlaufer S, Toews GB, Chen GH, Peters-Golden M. Differential regulation by leukotrienes and calcium of Fc g ?-receptor-induced phagocytosis and Syk activation in dendritic cells vs. macrophages. J Leuk Biol . 2006 Jun;79(6):1234-41.

13. Malani A, Aronoff DM, Bradley S, Kauffman CA . Cardiobacterium hominis endocarditis: two cases after endoscopy and a review of the literature. Eur J Clin Micro Infect Dis. 2006 Sep;25(9):587-95.

14. Aronoff DM, Carstens JK, Chen GH, Toews GB, Peters-Golden M. Differences between macrophages and dendritic cells in the cyclic AMP dependent regulation of lipopolysaccharide-induced cytokine and chemokine synthesis. J Interferon Cytokine Res. 2006 Nov;26(11):827-33.

15. Ballinger MN, Aronoff DM, McMillan TR, Cooke KR, Olkiewicz K, Toews GB, Peters-Golden M, Moore BB. Critical role of prostaglandin E 2 overproduction in impaired pulmonary host response following bone marrow transplantation. J Immunol. 2006 Oct 15;177(8):5499-508.

16. Mulla ZD, Gibbs SG, Aronoff DM. Correlates of length of stay, cost of care, and mortality among patients hospitalized for necrotizing fasciitis. Epidemiol Infect . 2007 Jul;135(5):868-76..

17. Huang S, Wettlaufer SH, Hogaboam C, Aronoff DM, Peters-Golden M. Prostaglandin E 2 inhibits collagen expression and proliferation in patient-derived normal lung fibroblasts via E prostanoid 2 receptor and cAMP signaling. AJP: Lung Cell Mol Physiol . 2007 Feb;292(2):L405-13.

18. Malani AN, Aronoff DM. A complicated Pseudomonas aeruginosa bone and soft tissue infection following etanercept therapy. Infect Dis Clin Practice. 2007 15(1): 63-65.

19. Aronoff DM, Peres CM, Serezani CH, Ballinger MN, Carstens JK, Coleman N, Moore BB, Peebles RS, Faccioli LH, Peters-Golden M. Synthetic prostacyclin analogs differentially regulate macrophage function via distinct analog-receptor binding specificities. J Immunol . 2007 178(3):1628-34.

20. Frantz FG, Rosada RS, Peres CM, Turato WM, Coelho-Castelo AAM, Ramos SG, Aronoff DM, Silva CL, Faccioli LH. The immune response to toxocariasis does not modify susceptibility to Mycobacterium tuberculosis infection. Am J Trop Med Hygiene. 2007 Oct; 77(4):691-8.

21. Nuwayhid ZB, Aronoff DM, Mulla ZD. Blunt trauma as a risk factor for group A streptococcal necrotizing fasciitis. Ann Epidemiol. 2007 Nov; 17(11):878-81.

22. Serezani CH, Chung J, Ballinger MN, Moore BB, Aronoff DM, Peters-Golden M. Prostaglandin E 2 suppresses bacterial killing in alveolar macrophages by inhibiting NADPH oxidase. Am J Respir Cell Mol Biol. 2007 Nov; 37 (5): 562-70.