BLRD Research Career Scientist Award Application

Central Arkansas Veterans Hlthcare Sys, North Little Rock AR

Investigators

Linked publications & trials

Abstract

I have been associated with VA since 2005 and have been a VA Merit award funded investigator since 2012. I study lipid metabolism and signaling in cardiovascular and metabolic disease with a focus on functional validation of the PLPP3 lipid phosphatase gene which we cloned in the late 1990s as a determinant of heritable cardiovascular disease risk. Our research has identified a lipid signaling pathway that promotes vascular inflammation and associated pathologies including atherosclerosis and calcific aortic valve disease, both of which have a higher incidence in Veterans than the general population. Our findings suggest new approaches for diagnosis and therapeutic management of these conditions. I have authored 287 peer reviewed research reports with a total of ~25,000 citations (~70 papers are cited more than 100 times, 6 have more than 500 citations) and this includes (in most cases as a VA affiliated investigator) publications in highly selective journals. I have a strong record of professional service, local and national service to VA and of collaboration with other VA investigators (61 publications with 6 different researchers). My laboratory has been a productive training environment for pre- and post-doctoral fellows who have been recognized by highly competitive awards including NIH F and K series grants and some of these individuals are now successful independent established academic investigators. To support our lipid research, and with VA support for two Shared Equipment Evaluation Program grants, I developed expertise in biomedical mass spectrometry which is now a major focus of my program. Through my role as core facility director and my association with the NIEHS supported Superfund and Environmental Diseases Core Centers at the University of Kentucky I became actively involved in development and application of analytical methods to study human health effects of exposure to environmental chemicals. This is the area of my VA research that I highlight in this application. Exposures to chemicals in the environment are an acknowledged determinant of health risk and a particular concern for veterans and active-duty military personnel as recently acknowledged by the Honoring our Promise to Address Comprehensive Toxics Act of 2022 (PACT-Act). Our analytical laboratory at CAVHS supports VA and DOD funded efforts to understand health effects of exposure to per and polyfluorinated alkyl substances (PFAS) which are manmade surfactant chemicals with widespread use for military firefighting. Exposure to high levels of PFAS is associated with increased risks of several cancers, dyslipidemia, endocrine and immune dysfunction in exposed individuals. Our primary project examines PFAS exposure in military firefighters and construction workers enrolled in the Million Veteran Program (MVP) and its progenitor the Millennium Cohort. Building on this work we are developing a facile, inexpensive, minimally invasive approach to monitor Service Member exposure to different classes of environmental chemicals using finger stick blood collection, dried blood spots, and large-scale targeted and untargeted analytical methods. This will eventually enable routine biomonitoring and screening of veterans and service members to support creation of a longitudinal exposure data repository. This would become a central component of larger scale assessment of environmental chemical exposures in military populations to inform strategies to mitigate risk in exposed individuals. These are necessarily team-based efforts where we our role is to provide accurate measurements of circulating environmental chemicals that are then used by statisticians and epidemiologists using multivariate models to identify associations between environmental chemical exposures and risk of non-communicable diseases. My efforts at CAVHS are well aligned with the intent of VA to establish a managed research portfolio in the broad area of Environmental Exposure (Military Exposure Research Program) and with VA/DOD involvement in the Cancer Moonshot Initiative notably the Project for Military Exposures and Toxin History Evaluation in US Service Members (PROMETHEUS). The Career Scientist Award would support my effort on these projects.