Brain, Behavioral, and Mental Health Research Career Scientist Award Application

Chronic multi-symptom illnesses (CMI) are complex and poorly understood diseases principally characterized by fatigue, pain, and problems with cognitive function. For Veterans, these diseases are collectively referred to as Gulf War Illnesses (GWI) and more recently post-acute sequelae of SARS Cov-2 (PASC). GWI affect ~250,000 Gulf War Veterans (GVs) (25-35% of the 1991 GV population), with nearly 50% of GVs seeking VA clinical care and nearly 40% receiving disability compensation. PASC affects nearly 45% of Veterans who were infected with the COVID-19 virus during the pandemic. To date, the causes of Veterans' long-term symptoms are not known, and as a result, no efficacious treatments are available. The general focus of my research is to determine the mechanisms that act to maintain chronic multi- symptom illnesses (CMI) - such as myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), GWI, and PASC; with a career goal of improving the health and quality of life of Veterans. My and my colleagues' research has shown that multiple physiological systems are dysfunctional in both GVs and civilians with CMI. Moreover, dysfunction within these systems is magnified and symptoms are exacerbated following an exercise challenge (i.e., post-exertion malaise [PEM]), providing a controllable model for their study. Thus, a central hypothesis of my research is that dysfunction across multiple physiological systems interacts to produce and maintain the symptoms of GWI, and this dysfunction is best studied by challenging physiological systems and testing how they interact. I have also shown that being physically active has a potential protective effect against both the identified deficits and the symptoms of these diseases. Thus, my research can inform non-pharmacological therapies that can be used to safely treat these diseases. My current VA-sponsored research directly tests our multisystem hypothesis by comparing GVs with GWI to healthy GVs across multiple physiological systems at rest and following acute exercise challenge. We are using advanced statistical methods to test whether interactions among multiple systems significantly explain symptoms of GWI. Capitalizing on the expertise of my lab and that of my collaborators, we test: 1) central nervous system regulation using structural and functional magnetic resonance imaging; 2) autonomic regulation using brain doppler methods for cerebral blood flow measurement; 3) immune and metabolic regulation using measures of gene expression, metabolomics, and proteomics from blood; 4) gut dysbiosis using bacterial and metagenomic sequencing; 5) neuroinflammation using positron emission tomography; and 6) symptom measurement using validated instruments to assess pain, fatigue, and cognition. My research appears in high impact journals across multiple disciplines (e.g. Sports Medicine: Medicine and Science in Sports and Exercise - Impact Factor: 4.5; pain science: Pain - Impact Factor: 6.0). To date, I have published ~130 papers, 167 abstracts, and have given 76 invited presentations (Total Citations: 9842; h-index, 53; i10-index: 102 Source: Google Scholar; 8/2025). I have a strong and established track- record of collaboration within the VA, nationally and internationally. These collaborations have enriched my research program and benefited the overall mission of the VA. I have served as an Associate Editor for Medicine and Science in Sports and Exercise and on numerous VA and NIH committees and grant review panels. I have successfully mentored junior scientists at all levels, most moving on to independent careers in Academia and Medicine. I have mentored several Career Development Awardees, and I have received teaching and mentoring awards for my efforts. In summary, the goals of my research program are directly in line with the mission of the Department of Veterans Affairs to care for those who have served this country, and thus I believe that I am well-qualified for a Research Career Scientist Award.