Pharmacology & Toxicology
Dr. Neera Tewari-Singh
B307 Life Sciences
1355 Bogue Street
East Lansing, MI 48824
- 1991 - BSc., Botany, Chemistry and Zoology, Lucknow University, India.
- 1993 - MSc., Life Sciences, Jawaharlal Nehru University, New Delhi, India.
- 2001 - Ph.D., Molecular Biology, Jawaharlal Nehru University, New Delhi, India. Ph.D. research was also conducted at the Institute of Molecular Genetics, Leibniz University Hannover, Germany
- 2002-2003 - Senior Research Fellow, Jawaharlal Nehru University, New Delhi, India and German Academic Exchange Service (DAAD) Research Fellow, Institute of Molecular Genetics, University of Hannover, Germany
- 2003-2006 - Postdoctoral Fellow, Colorado State University
- 2006-2012 - Research Associate, Toxicology, University of Colorado Denver
- 2012-2013 - Instructor, Toxicology, University of Colorado Denver
- 2014-2018 - Assistant Professor Research, Toxicology, Department of Pharmaceutical Sciences, University of Colorado Denver
- 2019-present - Assistant Professor, Pharmacology & Toxicology, Michigan State University Affiliated Faculty-Institute of Integrative Toxicology, Michigan State University
Technological advances and increasing industrialization pose an enhanced risk of occupational and/or accidental exposure to chemical agents in addition to their potential use in warfare and terrorism. The major long-term goal of research in my lab is to pursue both basic and translational studies to develop approved and more effective targeted countermeasures against injuries from chemical threat agent exposures. My lab research focus is on understanding mechanisms of toxicity and inflammation from mainly dermal and ocular exposures to chemical agents employing state-of-the-art molecular techniques and systems toxicology approaches. Developing effective and targeted medical interventions is a critical component of the modern global strategy to overcome the challenges of chemical emergencies in both civilian and military populations, making our research highly significant. In my lab, we integrate clinical and biological responses, molecular toxicology, biochemistry, signal transduction, immunology, imaging, and cutting-edge systems toxicology ‘omics’ tools to elucidate toxic mechanisms mainly related to inflammation, DNA damage and oxidative stress. For these studies, we employ in vivo (mice, rats, rabbits and mini-pigs), ex vivo (rabbit and human tissues) and in vitro (cell culture) model systems.
Major Current Projects
- Elucidate Mechanisms to Identify Therapeutic Targets and Targeted Therapeutic Approaches to Counteract Toxicity from Phosgene Oxime Skin Exposure. Vesicating chemical agents cause severe respiratory, skin, and ocular injuries. Phosgene Oxime (CX; dichloroform oxime), is an urticant or nettle agent grouped with vesicating agents; although, it causes more severe damage than other vesicants, owing to its highly reactive nature. Stockpiled during World War II, CX is a potent chemical weapon that poses a threat of exposure; both, alone and with other chemical agents. In March 2019, the FBI entered an Oklahoma City apartment and found massive amounts of manufactured CX, which could cause serious health hazard and chemical emergency. It is rapidly absorbed through the skin leading to an immediate skin irritation, erythema, blanching (whitening), itching hives, necrosis, and severe systemic toxicity and mortality. Even though it is one of the most notorious chemical toxicants, it is one of the least studied chemical warfare agents with no specific antidote available. To overcome these limitations, our completed and ongoing studies are directed towards the development of a relevant cutaneous CX exposure mouse injury model to elucidate the mechanisms of CX toxicity. We are studying if mast cell activation and mediators like histamine are novel targets for therapeutic intervention to counteract toxicity from CX cutaneous exposure. We will further investigate whether blocking these targets with antihistamines and/or epinephrine in established mouse toxicity models, will assist to mitigate CX-induced skin morbidity and mortality.
- Mast Cells in Sulfur Mustard Exposure: Novel targets for modulation to develop therapies against the long-term health effects in Gulf War Veterans. It is reported that during the Gulf War (GW; 1990-1991) exposure of veterans to chemicals like pyridostigmine bromide, pesticides, oil well fires, sarin and mustard gas or their combinations are most likely associated with Gulf War Illness (GWI). Our research is focused on identifying a novel immune mechanism of sulfur mustard [mustard gas; bis(2-chloroethyl) sulfide); SM] pathophysiological effects that could contribute to GWI. Mast cells are well known to contribute to allergic inflammatory diseases and also have wide ranging effects on many physiological systems that are affected in Gulf War veterans illness. Importantly, there are clinical therapeutics targeted towards mast cells and their products that could be beneficial in GWI patients, therefore, we aim to uncover a novel mechanism of SM toxicity (using its surrogate nitrogen mustard) that is mediated by mast cells and which could also be applicable to other chemical exposures in GWI.
- Elucidating the role of aryl hydrocarbon receptor in polycyclic aromatic hydrocarbons-induced skin inflammatory diseases for targeted treatment strategies. The prevalence of skin inflammatory diseases such as atopic dermatitis (AD) and psoriasis is increasing worldwide affecting lives of millions of individuals. Exposure to environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs; major environmental pollutant in automobile exhaust, cigarette smoke, many foods and industrial waste) are reported to contribute to the prevalence and exacerbation of these skin inflammatory diseases. Although dysregulated immune responses appear to be the root cause of disease, the mechanisms by which PAHs initiate skin inflammatory diseases remain unclear. Emerging evidence suggests that the aryl hydrocarbon receptor (AhR), a ligand-activated transcription factor, is an important player in skin integrity and skin immunity and its activation can modulate inflammatory skin lesions. The objective of this study is to investigate the pathophysiology and metabolic signature (metabolomics) in mouse skin following polycyclic aromatic hydrocarbon (PAH) exposure and explore Aryl hydrocarbon receptor (AhR)-related signaling pathways in skin inflammatory disease psoriasis and which can exacerbate from PAH exposure.
- Toxicity mechanisms in the cornea from ocular exposure to toxic chemicals and treatment strategies.
- Elucidate cornea toxicity due to nitrogen mustard (NM) and chloropicrin (CP) and other toxic chemicals’-induced oxidative stress and inflammation, which would help identify specific biomarkers and pathways in vesicating agent/pesticide and potential warfare agents’ -induced ocular injury.
- Utilize supersaturated oxygen emulsion treatment and /or anti-inflammatory agents in conjunction with an eye cup/wound chamber to preserve tissue and improve outcomes following ocular trauma.
Selected Awards and Fellowships
- 2019 - Michigan State University, Academic Communications Fellowship
- 2018 - Society of Toxicology, Dermal Toxicology Speciality Section, Annual Paper of the Year Award
- 2017- Society of Toxicology -Taylor and Francis Prize for the outstanding paper in Ocular Toxicology published in Cutaneous and Ocular Toxicology
- 2016 - Society of Toxicology-Association of Scientists of Indian Origin, Young Investigator Award
- 2013 - Society of Toxicology - Association of Scientists of Indian Origin, Best abstract Award
- 2012 - Society of Toxicology, Dermal Toxicology Speciality Section, Stratacor Award for Research and Presentation
- 2019-2010 - National Institutes of Health (NIH)-Countermeasures Against Chemical Threats Young Investigator Award
- 2008 - Outstanding Postdoctoral Research and Oral Presentation Award at the University of Colorado Denver Skaggs School Pharmacy and Pharmaceutical Sciences Retreat
- 2003 - DAAD (German Academic Exchange Service) Fellowship and Research visit, Institute of Molecular Genetics, Leibniz University, Hannover, Germany
- 1997 - DAAD Fellowship for Ph.D. research in biotechnology and molecular biology at the Institute of Molecular Genetics, Leibniz University Hannover, Germany
- 1993 - Jawaharlal Nehru University-University Grants Commission, Junior and Senior Research Fellowship
- 2019 - Vice President-Dermal Toxicology Specialty Section, Society of Toxicology
- 2018-2019 - Vice President Elect-Dermal Toxicology Specialty Section, Society of Toxicology
- 2017-2019 - Treasurer, Ocular Toxicology Specialty Section, Society of Toxicology
- 2016-2018 -Treasurer-Secretary, Dermal Toxicology Specialty Section, Society of Toxicology
- 2014-2016 - Junior and Senior Councilor, Dermal Toxicology Specialty Section, Society of Toxicology
- 2018-present - Editorial Board, Cutaneous and Ocular Toxicology, Francis and Taylor Journal
- 2019 - Member, Faculty Advisory Committee, Department of Pharmacology and Toxicology, Michigan State University
- 2018 - Member, Faculty Engagement and Accountability Committee, School of Pharmacy, University of Colorado Denver
- 2017-2018 - Grant Review Panel for the Colorado Clinical and Translational Sciences Institute (CCTSI) programs
- 2018 - Chair and organizer ‘Continuing Education Course’ session “Beauty of the Skin Is in the Eye of the Beholder: A Basic Course on Dermal and Ocular Toxicology” for the Society of Toxicology 2019 meeting
- 2017- Reviewer, U.S. Environmental Protection Agency Draft Chemical Specific Provisional Advisory Level, Technical Support Document for toxic agents
- 2015 - Member, Career Panel Academia, Committee on Diversity Initiatives, Undergraduate Education Program, Society of Toxicology
- Member, Society of Toxicology
- Member, The Association for Research in Vision and Ophthalmology
- Member, The American Society for Pharmacology and Experimental Therapeutics