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Dr. David Aronoff

Description of Research: David M. Aronoff

Our lab studies immunology, clinical pharmacology, and infectious diseases with a focus on the role of eicosanoids in regulating innate immunity.

Primarily we explore how one class of eicosanoids, the prostaglandins, modulates host-microbial interactions between bacterial pathogens and innate immune cells. Macrophages, neutrophils, and epithelial cells are the cellular participants under closest observation. For macrophages (and neutrophils) our focus is on the regulation of 3 primary functions: (1) receptor-mediated recognition & phagocytosis of bacteria; (2) mechanisms of intracellular killing of bacteria; and (3) the production of inflammatory mediators (such as cytokines, chemokines, & lipids). Our work in epithelial cells centers on the regulation & functions of antimicrobial peptides.

Our lab has two major projects:

1. The regulation of female reproductive tract innate immunity by prostaglandin E2 (PGE2). This work involves both in vitro and in vivo investigations into the ways in which PGE2 modulates the host response to bacterial endometritis. A recent area of interest has been trying to understand the pathogenesis of clostridial endometritis associated with the clinical use of the PGE2 analogue misoprostol.

2. The immunoregulatory role of PGE2 in the lung. PGE2 has immunosuppressive properties, particularly against cells involved in innate immunity like macrophages. Our lab has helped define the ways by which PGE2 produced in the lung impair host defenses against bacterial pathogens to increase the risk for (and severity of) pneumonia. This is most relevant in certain clinical circumstances characterized by an exaggerated production of PGE2. Such clinical conditions include malnutrition, advanced age, solid organ and stem cell tranplantation, and HIV. This work has a major emphasis on the intracellular signaling cascades within alveolar macrophages that are responsible for PGE2's effects on phagocytosis, bacterial killing, and inflammatory mediator generation. This work is done in close collaboration with the laboratory of Dr. Marc Peters-Golden in the Division of Pulmonary & Critical Care Medicine.

We are always interested in hearing from potential graduate students or post-doctoral fellows.

This lab is fun, friendly, and highly productive.

If you would like to learn more about our lab, please send Dr. Aronoff an e-mail: daronoff@umich.edu


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