Diversity Supplement to Impact of Chronic Alcohol Consumption on the Functional and Epigenetic Landscapes of Monocytes and their Progenitors

Project Summary/Abstract Chronic heavy drinking (CHD) is associated with multiple adverse health effects including increased incidence of liver disease, cardiovascular disease, cancer, and/or infectious disease. Given the increased incidence of viral, bacterial, and/or fungal infections often seen in patients with CHD, this suggests that alcohol can have a significant impact on the host immune response and host defense. The Messaoudi laboratory is in the forefront of the field examining alcohol’s effects on the immune system and has shown that the most dramatic and consistent changes are evident in the innate immune arm. They have shown in a clinically relevant non- human primate (NHP) model of CHD that there is a significant defect in the myeloid lineage. Recently they have extended these studies to employ a multi-omic examination of alveolar macrophages and show a similar phenotype. The purpose of this diversity supplement is to extend this work and provide key support for Dr. Jamie Sturgill. She will use this supplement to examine the role of ceramides in alveolar macrophage dysfunction in CHD in both NHP and patients with CHD. Previous work by the Sturgill lab has shown that ceramide is a critical sphingolipid in the lung and that alterations of ceramide signaling lead to increased ROS production, macrophage inflammatory responses, cellular death, and pulmonary dysfunction. Thus, ceramide is a logical extension of the work in the parent RO1. This supplement will allow her the chance to work with Dr. Messaoudi for three years in a focused and mentored project to learn cutting edge techniques such as single cell RNA sequencing and ATAC-sequencing and provide pivotal training to submit her own RO1 to NIAAA for future projects looking at the effects of CHD on pulmonary disease.