Associate Professor
Department of Biology
CB#3280
4352 Genome Sciences Building
919-962-7010
Research
Development and function of tissue-resident macrophages
Macrophages are highly dynamic and widespread blood cells that play many important functions in vertebrates. They are the main phagocytes throughout the body, responsible for clearing away dying cells, damaged tissue, and pathogens, to maintain tissue integrity. Macrophages circulate in the bloodstream as monocytes or are stationed in strategic locations of the body as tissue macrophages where their phagocytic roles are critical, such as microglia in the brain, Kupffer cells in the liver, Langerhans cells in the skin, and osteoclasts in the bone. Overall, the developmental process by which macrophages take residence and differentiate into tissue macrophages remains poorly understood. We are investigating the transcriptional and cellular regulations underpinning the differentiation and function of diverse tissue macrophages.
Cell-cell interactions between macrophages and the nervous system
The influence of macrophages on the development and homeostasis of various organs can be far-reaching. Yet the normal roles and mechanisms of macrophages and microglia in the healthy body and brain remain far less understood than their functions in disease and injury. Of particular interest is the function of microglia in the healthy brain. Although not well understood, they have been implicated in shaping brain circuitry and possibly affecting animal behavioral outcomes. Outside of the brain, other tissue macrophages also associate with neuronal networks, but the significance and consequence of this interaction remains an open and underexplored area. We are investigating the roles and mechanisms tissue macrophages have on the central and enteric nervous systems, which can elucidate general and specific principles by which the innate immune system modulates different aspects of the vertebrate nervous system.
Mechanisms that prevent inappropriate macrophage activation
There is a critical need to define essential mechanisms that prevent inappropriate innate immune activation to understand and treat autoinflammatory and autoimmune conditions. We are taking an unbiased forward genetics approach to address this challenge. We have developed a newly-designed assay to reveal for the first time genes that are required to prevent unprovoked inflammation. Our long-term goal is to dissect single-cell and population level control of macrophage states. An area of interest includes whether internal metabolic changes can dysregulate macrophages and affect their functional states.
Our Approach
We develop and integrate cutting-edge technologies in live imaging, genetics, genome editing, functional genomics, behavioral neurosocience, and cell biology to uncover and understand innate immune functions in the development or function of tissue systems in the vertebrate body. At multiple scales from genes to cells and whole organism, we focus on tackling outstanding questions in macrophage biology primarily using the zebrafish model system with also interest in cross-species experimentation.
