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.