Neera Tewari-Singh Receives U01 Grant from the National Institutes of Health

November 14, 2019

IIT-affiliated faculty member, Neera Tewari-Singh, was recently awarded a $1.423 million U01 grant from the National Institutes of Health - Countermeasures Against Chemical Threats Program and National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) for her project, "Targeted Therapeautic Approaches to Counteract Toxicity from Phosgene Oxime Skin Exposure." This three year grant will follow on her ongoing studies under the previously awarded R21 grant, "Phosgene oxime cutaneous toxicity and mechanisms to identify therapeutic targets." Dr. Tewari-Singh is an assistant professor in the Department of Pharmacology and Toxicology.

Dr. Tewari-Singh's project is a part of the comprehensive research CounterACT program, a trans-agency initiative launched by the Department of Health and Human services after the 9/11 attacks to improve the nation's emergency preparedness by engaging academia in countermeasures research for a more rapid and effective medical response during a civilian chemical emergency. The research under the NIH-CounterACT program is highly significant because technological advances and increasing industrialization pose an enhanced risk of occupational and/or accidental human exposure to chemical agents in addition to their potential international use in terrorism.

Phosgene oxime (dichloroform oxime, CX), classified as a vesicating agent, is a potent urticant or nettle chemical weapon which was first synthesized in 1929 and stored during World War II. In March of 2019, FBI found large quantities of CX in a Lawton Home in Oklahoma which could have been used on the civilian population. Compared to other vesicating agents like sulfur mustard (mustard gas), CX causes bewilderingly rapid effects on the skin, eye and mucus membranes including instant pain and prompt penetration. Even though it is considered the most harmful vesicant with real warfare and terrorist threat potential that can be used for rapid incapacitation and death, very little is known regarding the toxic effects of CX following its cutaneous exposure and its mechanism of action is unknown. Based on the results obtained from current studies under Tewari-Singh’s R21 grant, the goal of this breakthrough U01 application is to investigate if mast cells are key players and molecular targets in CX toxicity and investigate whether blocking these targets in established mouse toxicity models, will assist to mitigate CX- induced skin morbidity and mortality resulting from its cutaneous exposure. In addition, Dr. Tewari-Singh anticipates to identifying a therapeutic strategy that can target mast cell activation and release of histamine to mitigate CX-induced skin injury including urticaria and mortality from CX cutaneous exposure.

"This grant is extremely important for the ongoing study on CX in my lab and my career in the field of chemical medical defense research," commented Tewari-Singh. "It is a great honor to receive this U01-CounterACT award since very few people are awarded these U01 grants and we are one of the only labs conducting research on CX. Outcomes from this study will be the first major insight into CX-induced toxicity and related mechanisms following its cutaneous exposure. The overall impact of the ongoing research is very promising with the goal of further optimizing any targeted therapeutic agent/s identified under the current NIH-CounterACT U01 funding, which can be further optimized for treatment to enhance the nation’s medical response capabilities for rapid medical intervention during any potential civilian chemical emergencies due to vesicating/nettle agents exposure."