Nawajes Mandal, PhD, professor of Ophthalmology at the University of Tennessee Health Sciences, has been awarded a $466,103 grant from the National Eye Institute (NEI), part of the National Institutes of Health, to investigate how chemical warfare agents, specifically blister agents like mustard gas, damage the eyes and cause long-term vision loss.
Blister agents like sulfur mustard (mustard gas), nitrogen mustard, lewisite and phosgene oxime are chemical weapons that have been used in warfare and remain a potential accidental exposure and terrorist threat today. These agents cause severe damage to the skin, lungs and eyes on contact.
The eyes are especially vulnerable. Exposure can cause immediate pain, sensitivity to light and corneal erosions, followed by long-term complications including scarring, abnormal blood vessel growth and blindness. Despite the serious risk these agents pose, there are currently no approved medical treatments to protect the eyes from this type of damage.
Dr. Mandal’s team will study sphingolipids, fatty molecules naturally present in cell membranes, which the team believes are central to the chain of events that causes both immediate and lasting eye damage after blister agent exposure. In earlier laboratory studies, the researchers exposed the eye surfaces of animal models to nitrogen mustard and observed severe inflammation, damage to the cornea and eyelid glands, near-total vision loss and signs of dry-eye disease. Early chemical signals pointed directly to the sphingolipid pathway as a key driver of the injury.
The new grant, funded through the NIH’s R56 mechanism for high-priority research in areas of significant public health need, will allow the team to expand its work to better understand pathobiology. Dr. Mandal is also collaborating with a defense research laboratory at Wake Forest University, which has the specialized capability to work with sulfur mustard, the real-world chemical threat agent, to determine whether it triggers the same biological pathway as the nitrogen mustard used in laboratory settings.
“Sulfur mustard is the real threat, not nitrogen mustard,” Dr. Mandal noted. “We want to correlate whether they produce a similar type of injury at the molecular level.”
If the research proceeds as hoped, Dr. Mandal envisions a clear progression: establish reliable animal models, identify the precise molecular targets in the lipid signaling pathway and then begin developing countermeasures designed to interrupt the damage before it becomes permanent.
“Ultimately, the goal is developing medical countermeasures,” he said. “Once we establish the pathway, we are planning to develop some kind of countermeasure to target these lipid pathways.”
“This award reflects the excellence of the research taking place within our College of Medicine and a continued commitment to improving lives through discovery,” said Michael Hocker, MD, executive dean of the College of Medicine. “Dr. Mandal’s work has the potential to advance treatments that protect the vision of military personnel and civilians alike. It’s another example of how UT Health Sciences faculty are tackling complex health challenges with global impact.”
Dr. Mandal earned his PhD in plant molecular biology. During a postdoctoral fellowship at the University of Michigan’s Kellogg Eye Center, where he published around 10 papers across multiple subject areas, he first began focusing on sphingolipids, a family of molecules found in cell membranes that play a key role in inflammation and cell death. He later joined a lipid research lab in Oklahoma, where he carved out new scientific territory by applying sphingolipid research to the eye, a direction his mentor had never explored.
Today, his laboratory applies lipid biology not only to retinal diseases but also to ocular surface disorders, traumatic brain injury, diabetes, vascular cognitive impairment and other chronic diseases.
Dr. Mandal’s commitment to preventing blindness is deeply personal. As a young man in India, he watched his mother progressively lose her vision from severe diabetic retinopathy. Diagnosed with vision problems in her late thirties, she eventually became blind despite available treatments at the time.
“Seeing someone in your own family lose their sight changes the way you think about research,” he said. “It reminds me every day that our work is ultimately about helping patients and preserving quality of life.”
In 2025, Dr. Mandal was elected a Fellow of the Association for Research in Vision and Ophthalmology (FARVO), one of the highest honors bestowed by the world’s largest international organization dedicated to vision research.
His laboratory also pioneered the application of sphingolipid biology to numerous ocular diseases and in a 2025 publication demonstrated how tear lipids may serve as biomarkers for systemic conditions such as Gulf War Illness, expanding the role of the eye as a window into human health.
The newly funded NEI project represents another important step toward translating fundamental discoveries in lipid biology into therapies that could one day protect both military personnel and civilians from blinding chemical injuries.
“Our objective is not simply to understand the disease,” Dr. Mandal said. “It is to use that knowledge to develop treatments that preserve vision and improve people’s lives.”