EOHSI

Biographical Info

Research Areas

The overall focus of our research is immunotoxicology. We are particularly interested in inflammatory mechanisms of tissue injury. Our focus is on macrophages. Although the involvement of macrophages in protecting against invading pathogens and tumor cells is well documented, studies from my 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 rodent 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 animals to xenobiotics is associated with localized accumulation of macrophages. Moreover, macrophages isolated from the lung or liver of animals treated with tissue specific toxicants like 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 transgenic mice are being utilized. 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 and transcription factors. Much of our research has taken advantage of new technological developments in biochemistry, molecular biology and flow cytometry/image analysis.

Research Highlights

• Demonstrated that macrophages and inflammatory contribute to tissue injury induced by diverse pulmonary and hepatic toxicants
• Discovered that pulmonary injury induced by ozone is mediated by cytotoxic reactive nitrogen species
• Demonstrated that macrophage derived tumor necrosis factor –alpha plays a key role in both tissue injury and tissue repair
• Identified distinct macrophage subpopulations that play unique role in tissue injury and tissue repair

Recent Awards and Honors

• Society of Toxicology Education Award (2017)
• Society of Toxicology, Inhalation and Respiratory Specialty Section Career Investigator Award (2015)
• Society of Toxicology, Women in Toxicology Mentoring Award (2014)
• Rutgers University Board of Trustees Award for Excellence in Research (2009)
• Rutgers University Board of Trustees Award for Excellence in Research (2009)
• Dermatology Specialty Section, Society of Toxicology, “Paper of the Year” Award (2009)
• Named Roy Bowers Endowed Chair, Ernest Mario School of Pharmacy (2007)

Other Recent Activities

• Vice Chair-elect: Inhalation and Respiratory Specialty Section, Society of Toxicology (2016-present)
• Chair, Toxicology Division, American Society for Pharmacology and Experimental Therapeutics (2014-2015)
• Member, NIH Systemic Injury by Environmental Exposure (SIEE) Reveiw Panel (2013-present)
• Deputy Director NIEHS Center for Environmental Exposures and Disease (2009-present)
• Associate Editor, Toxicology and Applied Pharmacology (2001-present)
• Director Flow Cytometry/Cell Sorting and Confocal Microscopy Core Facility, EOHSI (1986-present)

Recent Publications

1. Gowdy, KM, Laskin, DL. Resolution of inflammation in xenobiotic-induced mucosal injury and chronic disease. Toxicol Appl Pharmacol. 2023; :116455. doi: 10.1016/j.taap.2023.116455. PubMed PMID:36907382
2. Herbert, J, Kelty, JS, Laskin, JD, Laskin, DL, Gow, AJ. Menthol flavoring in e-cigarette condensate causes pulmonary dysfunction and cytotoxicity in precision cut lung slices. Am J Physiol Lung Cell Mol Physiol. 2023;324 (3):L345-L357. doi: 10.1152/ajplung.00222.2022. PubMed PMID:36692165 PubMed Central PMC10026991
3. Malaviya, R, Gardner, CR, Rancourt, RC, Smith, LC, Abramova, EV, Vayas, KN, Gow, AJ, Laskin, JD, Laskin, DL. Lung injury and oxidative stress induced by inhaled chlorine in mice is associated with proinflammatory activation of macrophages and altered bioenergetics. Toxicol Appl Pharmacol. 2023;461 :116388. doi: 10.1016/j.taap.2023.116388. PubMed PMID:36690086 PubMed Central PMC9960611
4. Radbel, J, Meshanni, JA, Gardner, CR, Le-Hoang, O, Cervelli, J, Laskin, JD, Gow, AJ, Laskin, DL. Novel method to assess resident alveolar macrophage efferocytosis of apoptotic neutrophils by flow cytometry. Toxicol Appl Pharmacol. 2023;460 :116359. doi: 10.1016/j.taap.2022.116359. PubMed PMID:36565939 PubMed Central PMC9870943
5. Taylor, S, Murray, A, Francis, M, Abramova, E, Guo, C, Laskin, DL, Gow, AJ. Regulation of macrophage activation by S-Nitrosothiols following ozone-induced lung injury. Toxicol Appl Pharmacol. 2022;457 :116281. doi: 10.1016/j.taap.2022.116281. PubMed PMID:36244437
6. Sunil, VR, Vayas, KN, Radbel, J, Abramova, E, Gow, A, Laskin, JD, Laskin, DL. Impaired energy metabolism and altered functional activity of alveolar type II epithelial cells following exposure of rats to nitrogen mustard. Toxicol Appl Pharmacol. 2022;456 :116257. doi: 10.1016/j.taap.2022.116257. PubMed PMID:36174670
7. Murray, A, Banota, T, Guo, GL, Smith, LC, Meshanni, JA, Lee, J, Kong, B, Abramova, EV, Goedken, M, Gow, AJ et al.. Farnesoid X receptor regulates lung macrophage activation and injury following nitrogen mustard exposure. Toxicol Appl Pharmacol. 2022;454 :116208. doi: 10.1016/j.taap.2022.116208. PubMed PMID:35998709 PubMed Central PMC9960619
8. Joseph, LB, Gordon, MK, Zhou, P, Hahn, RA, Lababidi, H, Croutch, CR, Sinko, PJ, Heck, DE, Laskin, DL, Laskin, JD et al.. Sulfur mustard corneal injury is associated with alterations in the epithelial basement membrane and stromal extracellular matrix. Exp Mol Pathol. 2022;128 :104807. doi: 10.1016/j.yexmp.2022.104807. PubMed PMID:35798063
9. Jan, YH, Heck, DE, An, Y, Laskin, DL, Laskin, JD. Nitrogen Mustard Alkylates and Cross-Links p53 in Human Keratinocytes. Chem Res Toxicol. 2022;35 (4):636-650. doi: 10.1021/acs.chemrestox.1c00420. PubMed PMID:35312310 PubMed Central PMC9491701
10. Carnino, JM, Lee, H, Smith, LC, Sunil, VR, Rancourt, RC, Vayas, K, Cervelli, J, Kwok, ZH, Ni, K, Laskin, JD et al.. Microvesicle-Derived miRNAs Regulate Proinflammatory Macrophage Activation in the Lung Following Ozone Exposure. Toxicol Sci. 2022;187 (1):162-174. doi: 10.1093/toxsci/kfac025. PubMed PMID:35201360 PubMed Central PMC9041552

1. Sunil, VR, Vayas, KN, Fang, M, Zarbl, H, Massa, C, Gow, AJ, Cervelli, JA, Kipen, H, Laumbach, RJ, Lioy, PJ et al.. World Trade Center (WTC) dust exposure in mice is associated with inflammation, oxidative stress and epigenetic changes in the lung. Exp. Mol. Pathol. 2017;102 (1):50-58. doi: 1016/j.yexmp.2016.12.005. PubMed PMID:27986442
2. Francis, M, Groves, AM, Sun, R, Cervelli, JA, Choi, H, Laskin, JD, Laskin, DL. Editor’s Highlight: CCR2 Regulates Inflammatory Cell Accumulation in the Lung and Tissue Injury following Ozone Exposure. Toxicol. Sci. 2017;155 (2):474-484. doi: 1093/toxsci/kfw226. PubMed PMID:27837169
3. Francis, M, Sun, R, Cervelli, JA, Choi, H, Mandal, M, Abramova, EV, Gow, AJ, Laskin, JD, Laskin, DL. Editor’s Highlight: Role of Spleen-Derived Macrophages in Ozone-Induced Lung Inflammation and Injury. Toxicol. Sci. 2017;155 (1):182-195. doi: 1093/toxsci/kfw192. PubMed PMID:27708193
4. Mandal, M, Gardner, CR, Sun R, Choi H, Lad S, Mishin V, Laskin JD, Laskin DL. The spleen as an extramedullary source of inflammatory cells responding to acetaminophen-induced live injury. Toxicol Appl Pharmacol. 2017; 304: 110-120. doi:1016/j.taap.2016.04.019.  PMCID: PMC5147741
5. Venosa A, Malaviya R, Gow AJ, Hall L, Laskin JD, Laskin DL. Protective role of spleen-derived macrophages in lung inflammation, injury and fibrosis induced by nitrogen mustard. Am J Physiol Lung Cell Mol Physiol. 2015 Dec 15;309(12):L1487-98. doi: 10.1152/ajplung.00276.2015. PMID: 26475734 PMCID: PMC4683320 DOI: 10.1152/ajplung.00276.2015
6. Malaviya R, Sunil VR, Venosa A, Verissimo VL, Cervelli JA, Vayas KN, Hall L, Laskin JD, Laskin DL. Attenuation of nitrogen mustard-induced pulmonary injury and fibrosis by anti-tumor necrosis factor antibody/Toxicol Sci. 2015 Nov;148(1):71-88. doi: 10.1093/toxsci/kfv161.