ABSTRACT – Pilot Project 1 (Al-Hilal) In recent years several vaping products have hit the market, rapidly gaining consumers among adolescent, women of reproductive age, and especially pregnant women. Electronic nicotine delivery systems or e-cigarettes (e-Cigs) have become the preferred product to pregnant women due to the addiction and belief that they are much safer than traditional cigarettes. Preclinical studies have shown that nicotine (the principal e-liquid's ingredient) can cause vascular endothelial dysfunction, exacerbation of cerebral ischemia, and increase the susceptibility of secondary brain injuries. Likewise, chronic e-Cig vaping could be prodromal to cerebrovascular impairment and promote cerebrovascular conditions that favor the onset of post-ischemic secondary brain injuries. Developmentally regulated genes are more affected by smoke-exposure during prenatal life than adulthood. Maternal e-Cig exposure causes cognitive and epigenetic changes and worsens outcome to brain injuries in the offspring; however, their relationship with brain vasculature development is unknown. Widespread use of maternal e-Cig, alternative to tobacco smoke, strongly demands methodological studies to determine the real impact e-Cig on genes that regulate offspring’s brain angiogenesis and BBB during development. Thus, in response to the program scope and research objective of BBRC Pilot projects, we propose the following: 1) Assess the role of prenatal E-Cig exposure on the offspring brain endothelial cells and develop a panel of potential angiogenic biomarkers to determine harm of these products and 2) assess the molecular mechanisms that driving E-Cig-mediated impairment of the BBB in the offspring and its impact in a model of secondary brain injury. Overall, we will assess the impact of maternal e-Cig vaping on brain vascular development in the offspring. Our study will also focus on their impact on secondary brain injury risk and outcome. The dearth of regulatory guidelines, due to our limited knowledge on the health impact of maternal e-Cig vaping, has become a critical public and regulatory concern that we want to address with this research. ABSTRACT – Pilot Project 2 (Moschak) Substance use is a major driver of health disparities that exist between Hispanics and other segments of the population, and the relationships between behavioral endophenotypes and substance use can differ between Hispanic and non-Hispanic individuals. Several distinct behavioral endophenotypes predict addictive behavior, including impulsivity, distress tolerance, incentive salience, and novelty seeking. Importantly, these behaviors often interact or overlap in their ability to predict addictive behaviors. Thus, there is a strong need to test these behaviors in combination to give the most accurate relationship to substance use disorder. Furthermore, determining the neural substrates underlying these behaviors is an important step in developing effective treatments for add...