RCSV, SO and ABCT Joint Research Seminar

Session 1

Our present healthcare system focuses on treating people when they are ill rather than keeping them healthy. We have been using big data and remote monitoring approaches to monitor people while they are healthy to keep them that way and detect disease at its earliest moment presymptomatically. We use advanced multiomics technologies (genomics, immunomics, transcriptomics, proteomics, metabolomics, microbiomics) as well as wearables and microsampling for actively monitoring health. Following a group of 109 individuals for over 13 years revealed numerous major health discoveries covering cardiovascular disease, oncology, metabolic health and infectious disease. We have also found that individuals have distinct aging patterns that can be measured in an actionable period of time. Finally, we have used wearable devices for early detection of infectious disease, including COVID-19 as well as microsampling for monitoring and improving lifestyle. We believe that advanced technologies have the potential to transform healthcare and keep people healthy.

Session 2

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by elevated blood pressure in the pulmonary arteries, leading to right heart failure and death. Idiopathic PAH (iPAH), a subtype that develops spontaneously, is frequently associated with a pronounced inflammatory signature. In this study, we profiled peripheral blood mononuclear cells (PBMCs) and conventional dendritic cells (cDCs) from a cohort of iPAH patients, generating a high-quality single-cell dataset of 100,000 cells. Our analysis revealed immune dysregulation phenotypes linked to altered host-microbiome interactions, including decreased CD14 expression on monocytes, driving them towards an apoptotic phenotype, and a viral signature in cDCs associated with responses to human endogenous retrovirus K (HERV-K). These immune alterations corresponded with significant changes in circulating lymphocytes, notably a decrease in natural killer (NK) cells, an increase in regulatory CD4+ T cells, and a shift in the CD8+ T cell population, with a higher memory-to-naive cell ratio. Transcriptomic comparisons further uncovered a global signature of interferon-related signaling activation, aberrant cell migration, reduced NK and CD8+ T cell cytotoxicity, and altered cellular metabolism. These findings advance our understanding of the inflammatory landscape in PAH and identify potential therapeutic targets to address lymphocyte-associated pathology in this disease.