The Behrens Laboratory is mainly focused on 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.
There are a number of specific current projects that are active in the Behrens Lab:
- The role of IL-33/ST2 in Familial Hemophagocytic Lymphohistiocytosis (FHL): The lab recently showed 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.
- 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 an FHL like syndrome despite a congenital absence of IFNg receptor. The Behrens Lab is modeling this scenario in mice in order to dissect the immunologic mechanisms responsible for this effect.
- The role of the microbiome in cytokine storm: There is a large body of literature on the interaction between commensal organisms and immune regulation. The lab is examining the effect of this interaction of the development of cytokine storm. Current projects involve 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.
- 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. The lab is working to dissect the signaling that regulate this HO1 activity, and in which cells it is operative in murine models of cytokine storm.
- 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 altered hematopoiesis on the outcome of the cytokine storm itself.