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 such as acetaminophen and endotoxin in the liver and ozone, nano/microparticles, mustard vesicants, and chlorine is associated with localized accumulation of macrophages. Moreover, macrophages isolated from the lung or liver of animals treated with tissue specific toxicants 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 and molecular mechanisms mediating macrophage activation in the lung. This has involved investigations on signaling molecules, transcription factors, epigenetic regulators and microvesicles. We have also begun to assess the role of macrophages in tissue repair with a focus on impaired resolution of inflammation as a mechanism underlying tissue injury.

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

• Rutgers Biomedical Health Sciences Lifetime Distinguished Achievement Award (2022)
• Rutgers Biomedical Health Sciences Chancellor Distinguished Mentor Award (2021)
• American Society of Pharmacology and Experimental Therapeutics (ASPET), Toxicology Division Career Investigator Award (2021)
• Society of Toxicology, Mechanisms Specialty Section Career Investigator Award (2018)
• 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

• Member, Scientific Advisory Board, Research institute of Fragrance Materials (2023-present)
• President; Inhalation and Respiratory Specialty Section, Society of Toxicology 2018-2019
• 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) Review Panel (2014-2019)
• 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. Aggarwal, T, Bellomo, A, Stevenson, ER, Herbert, J, Laskin, DL, Gow, AJ, Izgu, EC. Protocol for detecting nitrative stress in biological lipid membranes in murine cells and tissues. STAR Protoc. 2024;5 (3):103268. doi: 10.1016/j.xpro.2024.103268. PubMed PMID:39215997 PubMed Central PMC11403049
2. Armeli, F, Mengoni, B, Laskin, DL, Businaro, R. Interplay among Oxidative Stress, Autophagy, and the Endocannabinoid System in Neurodegenerative Diseases: Role of the Nrf2- p62/SQSTM1 Pathway and Nutraceutical Activation. Curr Issues Mol Biol. 2024;46 (7):6868-6884. doi: 10.3390/cimb46070410. PubMed PMID:39057052 PubMed Central PMC11276139
3. Aleksunes, LM, Gray, JP, Meshanni, J, Laskin, JD, Laskin, DL. Repurposing FDA-approved drugs to treat chemical weapon toxicities: Interactive case studies for trainees. Pharmacol Res Perspect. 2024;12 (4):e1229. doi: 10.1002/prp2.1229. PubMed PMID:38965070 PubMed Central PMC11223991
4. Smith, LC, Abramova, E, Vayas, K, Rodriguez, J, Gelfand-Titiyevksiy, B, Roepke, TA, Laskin, JD, Gow, AJ, Laskin, DL. Transcriptional profiling of lung macrophages following ozone exposure in mice identifies signaling pathways regulating immunometabolic activation. Toxicol Sci. 2024;201 (1):103-117. doi: 10.1093/toxsci/kfae081. PubMed PMID:38897669 PubMed Central PMC11347782
5. Radbel, J, Meshanni, JA, Vayas, KN, Le-Hoang, O, Abramova, E, Zhou, P, Joseph, LB, Laskin, JD, Gow, AJ, Laskin, DL et al.. Effects of ozone exposure on lung injury, inflammation, and oxidative stress in a murine model of nonpneumonic endotoxemia. Toxicol Sci. 2024;200 (2):299-311. doi: 10.1093/toxsci/kfae062. PubMed PMID:38749002 PubMed Central PMC11285192
6. Bellomo, A, Herbert, J, Kudlak, MJ, Laskin, JD, Gow, AJ, Laskin, DL. Identification of early events in nitrogen mustard pulmonary toxicity that are independent of infiltrating inflammatory cells using precision cut lung slices. Toxicol Appl Pharmacol. 2024;486 :116941. doi: 10.1016/j.taap.2024.116941. PubMed PMID:38677601
7. Malaviya, R, Meshanni, JA, Sunil, VR, Venosa, A, Guo, C, Abramova, EV, Vayas, KN, Jiang, C, Cervelli, JA, Gow, AJ et al.. Role of macrophage bioenergetics in N-acetylcysteine-mediated mitigation of lung injury and oxidative stress induced by nitrogen mustard. Toxicol Appl Pharmacol. 2024;485 :116908. doi: 10.1016/j.taap.2024.116908. PubMed PMID:38513841
8. Gutierrez, B, Aggarwal, T, Erguven, H, Stone, MRL, Guo, C, Bellomo, A, Abramova, E, Stevenson, ER, Laskin, DL, Gow, AJ et al.. Direct assessment of nitrative stress in lipid environments: Applications of a designer lipid-based biosensor for peroxynitrite. iScience. 2023;26 (12):108567. doi: 10.1016/j.isci.2023.108567. PubMed PMID:38144454 PubMed Central PMC10746523
9. Laskin, JD, Ozkuyumcu, K, Zhou, P, Croutch, CR, Heck, DE, Laskin, DL, Joseph, LB. Skin Models Used to Define Mechanisms of Action of Sulfur Mustard. Disaster Med Public Health Prep. 2023;17 :e551. doi: 10.1017/dmp.2023.177. PubMed PMID:37849329 PubMed Central PMC11420828
10. Malaviya, R, Laskin, JD, Businaro, R, Laskin, DL. Targeting Tumor Necrosis Factor Alpha to Mitigate Lung Injury Induced by Mustard Vesicants and Radiation. Disaster Med Public Health Prep. 2023;17 :e553. doi: 10.1017/dmp.2023.178. PubMed PMID:37848400 PubMed Central PMC10841250

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.