The Center for Research on Cardiac Intermediate Filaments (CRCIF) fosters collaborative efforts aimed at clarifying the biological roles of intermediate filaments (IFs) using the heart as a material lab. This idea was sparked by the observation that IFs, which are protective in nature, are rapidly induced in virtually all forms of cardiac stress and therefore represent ideal, unexploited pharmacological targets to curb or prevent cardiac dysfunction.
Unlike the other two components of the cytoskeleton in metazoans (actin filaments and microtubules), IFs’s biological functions are only partly understood, and they are composed of different proteins in a cell-type-specific fashion.
The main protein component in the IFs of cardiac myocytes is desmin, which canonically maintain cellular and ultrastructural integrity, and mechanical stability.
Our research has identified consistent post-translational modifications (PTMs) of desmin -especially phosphorylation - in both animal and human heart failure (HF). These modifications are linked to impaired desmin proteostasis and cardiac dysfunction.
In fact, we also reported that disrupted desmin homeostasis, characterized by intracellular aggregates and pre-amyloid oligomers (PAOs), contributes to cardiomyocyte dysfunction.
Our goals are to: 1) understand how desmin PTMs and aggregation drive heart disease’s progression; and 2) use the heart as a material lab to understand IFs’ protective functions.
