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Edward M Behrens, MD
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Joseph Hollander Professor in Pediatric Rheumatology
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Department: Pediatrics
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- Immunology 6b
- Cell and Molecular Biology e
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Contact information
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Children's Hospital of Philadelphia
1e 3615 Civic Center Blvd
31 Room 1107A ARC
Philadelphia, PA 19107
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1e 3615 Civic Center Blvd
31 Room 1107A ARC
Philadelphia, PA 19107
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Office: 215-590-7180
32 Fax: 215-590-1258
32 Lab: 267-426-5278
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32 Fax: 215-590-1258
32 Lab: 267-426-5278
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Email:
behrens@email.chop.edu
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behrens@email.chop.edu
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Education:
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31 Johns Hopkins University, 1997.
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46 University of Pennsylvania School of Medicine, 2002.
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Permanent link21 7 BA 14 (Biology) c
31 Johns Hopkins University, 1997.
21 7 MD c
46 University of Pennsylvania School of Medicine, 2002.
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36c The Behrens Laboratory is mainly focused on the understanding the pathogenesis of Cytokine Storm Syndrome, a common pathologic endpoint of a heterogeneous group of initiating diseases. Cytokine Storm Syndrome results in multi-organ failure and a stereotypical immune response including increased serum ferritin and Interferon gamma that leads to the organ failure itself. The lab is interested in dissecting the initiating, propagating, and regulatory factors that determine the pace and outcome of cytokine storm. This is done using a number of different murine models including perforin deficient mice, repeated TLR9 agonist injections, and other murine systems of systemic inflammation. The ultimate goal of these investigations is to improve the lives of patients that suffer from cytokine storm syndromes by developing strategies for treatment and prevention.
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97 There are a number of specific current projects that are active in the lab. The following is a list of some representative long-term projects.
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187 1) The role of IL-33/ST2 in Familial Hemophagocytic Lymphohistiocytosis (FHL) – We have recently shown a novel role for IL-33 and its receptor ST2 in driving the fatal inflammation seen in FHL. Current projects include examining which cells types are responding to IL-33 to drive pathogenesis and the biochemical and cellular mechanisms by which IL-33 signals confer pathogenicity.
17a 2) The role of Interferon gamma (IFNg) in FHL – Although IFNg is classically thought to be a necessary pathogenic cytokine in FHL, there have been recent reports of patients who develop and FHL like syndrome despite a congenital absence of IFNg receptor. We are modeling this scenario in mice in order to dissect the immunologic mechanisms responsible for this effect.
211 3) The role of the microbiome in cytokine storm – There is a large body of literature on the interaction between commensal organisms and immune regulation. We are examining the effect of this interaction of the development of cytokine storm. Current projects are dissecting which commensal microorganisms alter immune function during cytokine storm, the cellular mechanisms by which such effects takes place, and the development requirements for microbiota/immune system interactions for cytokine storm pathogenesis.
172 4) The role of Heme-oxygenase 1 (HO1) in cytokine storm – Published work has suggested that the HO1 enzyme is responsible for the production of protective IL-10 in suppressing the negative effects of cytokine storm. We are working to dissect the signaling that regulate this HO1 activity, and in which cells it is operative in murine models of cytokine storm.
12d 5) Hematopoiesis during inflammation – Both lymphoid and myeloid development is dramatically altered during cytokine storm. We are currently dissecting the signals responsible for this alteration, and the downstream effects of alter hematopoiesis on the outcome of the cytokine storm itself.
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Description of Research Expertise
98 Keywords: Dendritic Cell, Toll-like receptor, Macrophage Activation Syndrome, Hemophagocytic Lymphohistiocytosis, Antigen Presentation8
36c The Behrens Laboratory is mainly focused on the understanding the pathogenesis of Cytokine Storm Syndrome, a common pathologic endpoint of a heterogeneous group of initiating diseases. Cytokine Storm Syndrome results in multi-organ failure and a stereotypical immune response including increased serum ferritin and Interferon gamma that leads to the organ failure itself. The lab is interested in dissecting the initiating, propagating, and regulatory factors that determine the pace and outcome of cytokine storm. This is done using a number of different murine models including perforin deficient mice, repeated TLR9 agonist injections, and other murine systems of systemic inflammation. The ultimate goal of these investigations is to improve the lives of patients that suffer from cytokine storm syndromes by developing strategies for treatment and prevention.
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97 There are a number of specific current projects that are active in the lab. The following is a list of some representative long-term projects.
8
187 1) The role of IL-33/ST2 in Familial Hemophagocytic Lymphohistiocytosis (FHL) – We have recently shown a novel role for IL-33 and its receptor ST2 in driving the fatal inflammation seen in FHL. Current projects include examining which cells types are responding to IL-33 to drive pathogenesis and the biochemical and cellular mechanisms by which IL-33 signals confer pathogenicity.
17a 2) The role of Interferon gamma (IFNg) in FHL – Although IFNg is classically thought to be a necessary pathogenic cytokine in FHL, there have been recent reports of patients who develop and FHL like syndrome despite a congenital absence of IFNg receptor. We are modeling this scenario in mice in order to dissect the immunologic mechanisms responsible for this effect.
211 3) The role of the microbiome in cytokine storm – There is a large body of literature on the interaction between commensal organisms and immune regulation. We are examining the effect of this interaction of the development of cytokine storm. Current projects are dissecting which commensal microorganisms alter immune function during cytokine storm, the cellular mechanisms by which such effects takes place, and the development requirements for microbiota/immune system interactions for cytokine storm pathogenesis.
172 4) The role of Heme-oxygenase 1 (HO1) in cytokine storm – Published work has suggested that the HO1 enzyme is responsible for the production of protective IL-10 in suppressing the negative effects of cytokine storm. We are working to dissect the signaling that regulate this HO1 activity, and in which cells it is operative in murine models of cytokine storm.
12d 5) Hematopoiesis during inflammation – Both lymphoid and myeloid development is dramatically altered during cytokine storm. We are currently dissecting the signals responsible for this alteration, and the downstream effects of alter hematopoiesis on the outcome of the cytokine storm itself.
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Description of Clinical Expertise
bf I am a Board Certified Pediatric Rheumatologist with a particular interest in autoinflammatory syndromes and Macrophage Activation Syndrome/Hemophagocytic Lymphohistiocytosis.1a 7 1d 1f
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