Studies

Rationale: Arterial inflammation manifested as atherosclerosis is the leading cause of mortality worldwide. Genome-wide association studies have identified a prominent role of HDAC (histone deacetylase)-9 in atherosclerosis and its clinical complications including stroke and myocardial infarction.

Objective: To determine the mechanisms linking HDAC9 to these vascular pathologies and explore its therapeutic potential for atheroprotection.

Methods and Results: We studied the effects of Hdac9 on ...

A rapid immune response to signals released from pathogens and injuries is critical for maintaining tissue integrity and restoring homeostasis. This response is largely mediated by the concerted action of pattern recognition receptors (PRRs). Such cooperativity has been described for Toll-like receptors (TLRs) and NACHT, LRR, and pyrin domain-containing protein 3 (NLRP3), but the underlying molecular mechanisms remain incompletely understood. Inflammasomes are multi-protein complexes defined by ...

Loss-of-function mutations in the homotrimeric serine protease HTRA1 cause cerebral vasculopathy. Here, we establish independent approaches to achieve the functional correction of trimer assembly defects. Focusing on the prototypical R274Q mutation, we identify an HTRA1 variant that promotes trimer formation thus restoring enzymatic activity in vitro. Genetic experiments in Htra1R274Q mice further demonstrate that expression of this protein-based corrector in trans is sufficient to stabilize ...