During the past two years, our group, along with Haibo Jiang, has used NanoSIMS imaging to investigate the mechanisms by which the fatty acid products of TRL processing move across capillary endothelial cells and into vital tissues (e.g., heart, adipose tissue). We showed that the movement of fatty acids into cardiomyocytes is extraordinarily rapid. Remarkably, capillary endothelial cells did not appear to be a barrier to fatty acid transport into myocytes and adipocytes.

We have also investigated mechanisms for the export of cholesterol from macrophages. By scanning EM, we found that macrophages release large numbers of 20–120-nm vesicular particles. By NanoSIMS imaging, these particles are enriched in the mobile and metabolically active “accessible” pool of cholesterol. We suspect that the release of cholesterol–rich particles plays an important role in cholesterol efflux by macrophages.

We also study the role of the nuclear lamins in health and disease. Nuclear lamins are building blocks for the nuclear lamina, a structural scaffolding for the cell nucleus. Several years ago, our group defined the in vivo functional relevance of lamin B1 and lamin B2, two key proteins of the nuclear lamina. Both proteins are essential for neuronal migration in the developing brain and for neuronal survival. We also work to understand genetic diseases caused by defective processing of prelamin A, with the goal of identifying effective treatment strategies.