Tewari-Singh Awarded R01 Grant by National Eye Institute

December 14, 2023

IIT-affiliated faculty member Dr. Neera Tewari-Singh was recently awarded a R01 grant from the National Eye Institute for her project, “Understanding Mustard Vesicants Distribution and Toxicity in the Eye Using In Vivo and In Silico Models.” Tewari-Singh will receive $1,380,587 to perform this research over the next three years.

For over 15 years the major long-term goal of Dr. Tewari-Singh’s research has been to pursue both basic and translational studies to develop approved and more effective targeted countermeasures and therapies against dermal and ocular injuries from chemical threat agent exposures. Mustard gas (sulfur mustard) has historically been one of the most commonly used chemical warfare agents and remains a potential agent of warfare and terrorism. Consequently, many governments and research agencies have prioritized researching and developing countermeasures to mustard gas toxicity. Tewari-Singh’s research has focused on discovering signaling pathways that could lead to mustard gas toxicity to identify the targeted therapeutic treatments that could help treat these exposures.

The eye is the most sensitive organ to mustard gas exposure, resulting in devastating biphasic ocular injury and impaired vision or blindness. The dose and time related severity of symptoms of this eye injury in mass casualty situations poses a challenge in mechanistic research and identification of therapeutic targets. Injury involving damage mainly to the cornea and possibly other ocular tissues is not well understood. With her new R01 grant, Tewari-Singh will be collaborating with Dr. Carrie German at CFD Research, a company that specializes in computational modeling. Her research will use in vivo studies and CFD Research’s existing in silico rabbit ocular model to determine how mustard gas and various other chemical agents penetrate the eye at various concentrations and timings. This is an exciting step in addition to her current in vivo research, that will use a synergistic in vivo-in silico approach to determine mustard vesicant eye distribution and the resulting corneal injury and repair mechanisms.

The combination of experimental and computational approaches will provide a more cost and time efficient platform for the evaluation of mustard vesicant exposure for multiple concentrations and durations. These studies will allow Tewari-Singh to answer a lot of questions on time- and tissue-dependent eye toxicity mechanisms by mustards that were previously unattainable using only in vivo methods. Her studies will also combine in vivo analyses of injury and repair pathology with time- and concentration-dependent transcriptomics (RNA sequencing analysis-based bioinformatics) to identify the biochemical changes and their associated pathways. The proposed study could serve as a more efficient and potentially more insightful novel approach to evaluate mustard vesicating agents’ induced tissue-specific toxicity mechanisms.

Tewari-Singh will use newly acquired data from these studies to further develop countermeasures and treatment modalities for the future, especially for mass casualty scenarios from eye exposure to chemical threat agents. This research can then be applied to predict toxicity and treatment modalities for exposures to other organs as well. 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 her research highly significant.