Professor II-Chair; Chair
Ph.D., Medical College of Virginia, 1980
Professional Summary/CV [.PDF]
Department of Pharmacology and Toxicology, Ernest Mario School of Pharmacy, New Brunswick; Rutgers
Areas of Interest
Nonspecific immunity and inflammation, role of macrophages and neutrophils and inflammatory mediators in tissue injury with particular focus on the liver and the lung.
Pharmacology, Toxicology, Pathophysiology, Molecular Medicine, Microbiology, Immunology.
Memberships and Professional Service
Member, Society of Leukoctye Biology, Society of Toxicology, American Association for Cancer Research, American Thoracic Society, American Association of Immunologists; Chair, Research Committeee, New Jersey Thoracic Society; Director, Analytical Cytometry/Image Analysis Facility Core, NIEHS-Center for Excellence in Environmental Health Sciences, UMDNJ/Rutgers University and The Cancer Institute of New Jersey (CINJ); Deputy Director, UMDNJ/Rutgers NIEHS Center of Excellence in Environmental Health Sciences; Member, Scientific Council, CINJ; Associate Editor, Toxicology and Applied Pharmacology; Editorial Board Member, Journal Toxicology and Environmental Health.
Grants, Honors, and Awards
Principal Investigator, National Institutes of Health, "Role of Kupffer Cells in Chemical Toxicity," 2006-2010; Principal Investigator, National Institutes of Health, "Activated Macrophages and Ozone Toxicity," 2002-2008; Co Investigator, National Institutes of Health, “UMDNJ/Rutgers University CounterACT Research Center of Excellence," 2006-2011; Burroughs Welcome Toxicology Scholar Award (1993-1998); Society of Leukocyte Biology Dolph Adams Most Cited Publication Award, 1999; Society of Toxicology Achievement Award, 1991; Society of Toxicology Publications Award, 1988; Society for Leukocyte Biology Young Investigator Award, 1989.
Academic Interests and Plans
The overall focus of our research is analysis of immune mechanisms of tissue injury. We are particularly interested in nonspecific immunity mediated by macrophages, which are critical cellular components of the host response to tissue injury. Although the involvement of macrophages in protecting against invading pathogens and tumor cells is well documented, recent studies from our laboratory have demonstrated that macrophages also have a dark side. Thus they can be activated to release excessive quantities of proinflammatory and cytotoxic mediators that actually promote tissue injury. An analysis of this process represents the main focus of our research. Two mouse models are being utilized to investigate the role of macrophages and inflammatory mediators in toxicity: the lung and the liver. In each of these tissues, we found that exposure of mice to xenobiotics is associated with localized accumulation of macrophages.
Moreover, macrophages isolated from the lung or liver of animals treated with tissue specific toxicants such as ethanol, acetaminophen, or ozone are “activated” to release increased quantities of inflammatory mediators such as tumor necrosis factor alpha, nitric oxide and superoxide anion. To analyze the role of these cytotoxic mediators in toxicity, both pharmacologic inhibitors and knockout mice are being utilized. Whereas in some model systems, both approaches result in similar results in others such as hepatic necrosis induced by acetaminophen administration, opposing results are obtained. Thus, in this model, anti-TNF-alpha antibody prevents toxicity, while TNF-alpha knockout mice were more sensitive to acetaminophen. These data suggest that there are limitations to the use of transgenic animals which may be related to compensatory alterations in cytotoxic mediators production and this is being investigated. Another aspect of our studies is to elucidate biochemical mechanisms mediating macrophage activation in the liver and the lung. This has involved investigations on signaling molecules such as MAP kinases, and transcription factors such as NF-kB, C/EBP and AP-1. Much of our research has taken advantage of new technological developments in biochemistry, molecular biology and flow cytometry/image analysis.