The overall goal of our research program is to develop high-impact research that directly addresses unmet medical needs of Veterans who served during the 1990-1991 Persian Gulf War and suffer from chronic multi-symptom syndrome or the Gulf War Illness (GWI).
Project 1: Amongst many causative factors, chronic exposure to organophosphate (OP) pesticides and low levels of Sarin are considered to be a leading cause for the development of GWI. We have recently developed a rat model of GWI neurological symptoms using DFP, a surrogate nerve gas agent. We have discovered chronic elevated calcium levels in GWI neurons and are identifying some of the molecular bases for these altered calcium dynamics in GWI. By using targeted agents to block these calcium imbalances we hope to provide effective GWI therapies for our Veterans.
Project 2: More than 20- years have elapsed since the end of the First Gulf War and it is unacceptable that we do not have effective therapies for GWI suffering Veterans. GW Veterans are frustrated and appear to scour internet sites that are now offering ketamine therapies for relieving depression. This is very dangerous and we owe it to our GW Veterans to scientifically test this and offer these therapies in a safe and effective manner. Our preliminary research is the first-one to indicate that in GWI rodent model, a single-dose of ketamine at low, sub-anesthetic concentrations, produces a rapid and long-lasting antidepressant effect.
Project 3: In GWI research, a central question of how a chemical exposure from 25-years ago could produce such a chronic multi-symptom illness to this day even when the causative factors are no longer present has not been satisfactorily answered. Epigenetic mechanisms respond to external stimuli such as environment, diet, experiences, and the effects of such exposures can become embedded in the genome to produce long-lasting changes in cellular regulation. We have identified chronic alterations in epigenetic (histone) modifications in response to organophosphate exposure that provides a causal link between organophosphate exposure during GW service and GWI development.
Project 4: GWI related OP exposures are not only associated sustained calcium levels but also exhibit a state of chronic CNS inflammation that correlate with neurological morbidities. We have taken a radical approach to treat GWI by "re-educating" microglia to return to a protective state that will reduce inflammation and the chronic CNS symptoms of GWI. Therefore, we will restore healthy neuroimmune cross-talk by redirecting the calcium communication disrupted from injury of neurons by OP agents. This project is conducted in collaboration with Dr. Jamie DeWitt at East Carolina University.