Research Areas

Classical monocytes are produced in the bone marrow and can give rise to non-classical monocytes that patrol the blood, or they can enter tissues to become macrophages or monocyte-derived dendritic cells (moDC). We have demonstrated that classical monocytes are more heterogeneous than previously appreciated, in part due to their diverse origins1. We showed that classical monocytes can be produced by granulocyte-monocyte progenitors (GMP) and monocyte-DC progenitors (MDP). Subsets we have described include neutrophil-like monocytes (NeuMo) and moDC-producing monocytes (DCMo). Studies from other groups have confirmed and built on our findings to demonstrate the importance of monocyte origins in shaping monocyte responses.

In ongoing studies, we are continuing to define the fates and functional diversity of monocytes, including how monocyte origins and sex differences shape the functional programming of monocyte subsets during differentiation. Defining the basic biology of monocyte subsets is informing our understanding of their diverse roles in homeostasis, pathogen defense, inflammatory diseases, cancer and more.

Microglia, the brain's resident macrophages, maintain brain health throughout life by supporting neurons and responding to injury and infection. However, they may contribute to neurodegeneration if their function is compromised or they respond inappropriately. We are studying microglial aging and their roles in neurodegenerative diseases such as Alzheimer's.

Recently, we have defined transcriptomic, metabolic and functional changes in microglia during aging. We observed more pronounced aging-associated changes in microglia from female mice compared to their male counterparts, including a shift in cell metabolism and increased production and activity of complement factors. In ongoing studies, we are dissecting the mechanisms underlying these aging-associated changes and sex dimorphism.

We are also interested in communication between blood cells in the periphery and microglia in the brain. We previously demonstrated that transplantation of young bone marrow cells rescues aging-associated cognitive decline2. We observed rejuvenation of recipient microglia rather than replacement by donor-derived monocytes, so we are investigating how signals from peripheral blood cells impact microglial function.