Innate immune responses in cardiac injury, atherosclerosis and related metabolic disorders.
We study three arms of the innate immune system: (1) The NLRP3 inflammasome, a platform for the post-translational activation of IL-1β. In addition to studies on the pathogenic consequences of activation of the NLRP3 inflammasome in CVD, we have projects where we investigate how the inflammasome is activated. (2) The role of the complement system in clinical and experimental atherosclerosis. (3) Effective resolution of inflammation is important to prevent progression of acute inflammation to non-resolving chronic inflammation. Inflammation resolution is a coordinated and active process, and we are currently examining how this is regulated in different forms of CVD.
DNA damage and repair in atherosclerosis and heart failure.
Aging, reactive oxygen species and chronic stress cause damage to both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) and this is proposed to contribute to development of non-communicable disease such as CVD. We believe that DNA damage and the associated DNA repair mechanisms are centrally involved in the pathogenesis of both atherosclerosis and heart failure by promoting non-resolving inflammation. We are currently examining this hypothesis experimentally, using mouse models that are deficient in DNA repair enzymes or have increased DNA repair activity.