Program Faculty

My laboratory investigates the innate immune system, specifically macrophages, which are critical cellular components of the host response to tissue injury and infection. Although the role of macrophages in protecting against invading pathogens and xenobiotics is well documented, studies from our laboratory have demonstrated that macrophages also have a dark side. Thus, they can become hyperactive, resulting in prolonged tissue injury and chronic disease. An analysis of this process represents the focus of our research. Currently, most of our work is focused on the lungs. We discovered that pulmonary exposure of rodents to xenobiotics is associated with localized accumulation of macrophages in the tissue. Moreover, macrophages isolated from the lungs of animals treated with toxicants (e.g., air pollutants, chemical warfare agents, radiation) release excessive quantities of inflammatory mediators such as tumor necrosis factor alpha, nitric oxide and superoxide anion, a response linked to exacerbated tissue injury and inflammatory lung disease. To analyze the role of macrophage-derived cytotoxic mediators in toxicity, both pharmacologic inhibitors and knockout mice are being utilized. Research in the laboratory is also centered on elucidating biochemical and molecular mechanisms mediating macrophage activation following toxicant exposure. In addition to investigations on transcription factors, lipids and cellular metabolism, we are studying epigenetic regulators of macrophage activation including noncoding RNAs. The overall goal of our research is to harness the pathologic activity of macrophages and redirect it towards promoting inflammation resolution and tissue repair.

Publications

NCBI Publications