Edward M Behrens, MD

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Assistant Professor of Pediatrics
Department: Pediatrics
Graduate Group Affiliations

Contact information
Room 1102 ARC
3615 Civic Center Blvd
Philadelphia, PA 19107
Office: 215-590-7180
Fax: 215-590-1258
Lab: 267-426-5278
Education:
BA (Biology)
The Johns Hopkins University, 1997.
MD (Medicine)
The University of Pennsylvania School of Medicine, 2002.
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Description of Research Expertise

Keywords: Dendritic Cell, Toll-like receptor, Macrophage Activation Syndrome, Hemophagocytic Lymphohistiocytosis, Antigen Presentation

The Behrens lab mainly focuses on dendritic cell biology and their function in normal and pathologic immune responses. In particular, we have developed an interest in Toll-like receptors (TLRs), a set of molecules on dendritic cells that recognize pathogens via common molecular motifs and initiate inflammatory responses. Within this theme of dendritic cell/TLR biology, the lab has two major arms of research:

1) TLR signal transduction – TLRs have classically been thought to signal cells to generate inflammatory responses via two major signaling conduits, the MyD88 and TRIF pathways. However, there are many modifying and regulatory pathways that intersect with these tow major TLR signaling cascades. We are interested in probing the role of tyrosine phosphorylation events, mediated by Syk and the adapter protein Slp-76 in modulating TLR function in dendritic cells and macrophages.


2) Macrophage Activation Syndrome – MAS is a rare, but fatal complication of a number of rheumatic, oncologic, infectious, and genetic disorders. In particular, 10% of patients with Systemic Juvenile Idiopathic Arthritis will develop fulminant, life-threatening MAS. The syndrome consists of a “sepsis-like” clinical picture, and the pathologic hallmark of the disease is the hemophagocytic macrophage. These are macrophages, typically found in the bone marrow, that are phagocytosing other live hematopoetic cells such as red blood cells, platelets, or leukocytes. The pathoetiology of MAS in poorly understood, but is thought to be in part due to excessive CD8+ T-cell/antigen presenting cell (APC) interaction, resulting in overwhelming inflammation. While the T-cell determinants of this pathologic interaction have been reasonably well characterized, the APC side has not. Which APC plays a role in the disease, what APC inflammatory mediators, and what signal transduction pathways are critical to disease all remain unanswered and are potential areas of therapeutic development. Furthermore, the physiologic role of the hemophagocyte remains debated. We have developed a novel model of MAS in the mouse that does not depend on a genetic mutation but rather on repeated TLR stimulation, replicating the inflammatory environment seen in the rheumatic diseases associated with MAS. We have identified a complex network of cytokines, including IFNg and IL-10, and cell types that contribute to disease. We are currently working our the regulatory mechanisms behind these cytokines and cells to both provide insight into the fundamental immunology of MAS and develop novel therapeutics. We are also using transcriptome analysis to investigate the function of hemophagocytes to better understand their role in MAS.
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Last updated: 08/21/2014
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