microscopy,
flow cytometry,
cell culture
monocytes,
macrophages,
dendritic cell,
atherosclerosis,
lymphatic vessels,
migration
My research laboratory carries out basic research on the differentiation and trafficking of
monocytes and antigen-presenting
dendritic cells. More recently, we have begun to study these cell types and their behavior in the context of
atherosclerosis.
One of the fascinating properties of
dendritic cells is their special capacity to efficiently emigrate out of tissues to
lymph nodes via
lymphatic vessels. Some of our research is directed to the study of basic mechanisms that regulate
dendritic cell development from
monocytes and the migration of
dendritic cells to
lymph nodes. These two fundamental lines of study now significantly influence our approach to studying
atherosclerosis. We have observed in multiple
model systems that
monocytes that become
dendritic cells readily emigrate out of tissues, usually via
lymphatic vessels, whereas
macrophages typically remain resident in the tissues where they form. To prevent the ongoing accumulation of
macrophages in tissues and to maintain homeostasis, we hypothesize that it is important that some
monocytes that enter a particular tissue continuously differentiate into
dendritic cells that in turn subsequently emigrate from that tissue. We have proposed that this homeostatic process breaks down in
atherosclerosis, such that monocyte-derived
dendritic cells fail to emigrate and consequently aberrantly accumulate within plaques, contributing to plaque progression. Conversely, we propose that restoring the emigration of these cells from plaques facilitates plaque regression. This proposal is based in part on evidence from a
model system that permitted us to trace whether and under what conditions cells emigrate from
lesions. We have recently developed new techniques to trace
monocyte fate within
atherosclerotic plaques that will allow us to focus further on the differentiation of plaque-infiltrating
monocytes to
dendritic cells and
macrophages and to identify mechanisms that affect their emigration from
lesions. For the foreseeable future, the laboratory will remain connected to the study of
monocyte biology and
dendritic cell migration in a normal, non-diseased setting, while increasingly mobilizing our efforts to address these topics in the context of
atherosclerosis.
