Evaluating Immunological Treatment and Prevention Strategies Using Single-Cell Genomics

Abstract

Single cell genomics have transformed our ability to profile human biology in depth and breadth. In chapter 2, we use scRNA-seq to profile pediatric inflammatory bowel disease, delineating distinct mechanisms of inflammation in each of the disease’s major subtypes. Using information regarding study participants’ clinical course, we characterize features associated with biologic treatment use and nonresponse. Here, pairing gene expression measurements with T cell receptor sequencing allows us to identify novel T cell receptor phenotypes that may be responsible for incompletely understood differences in immunological presentation and differences in response to first-line treatment in inflammatory bowel disease. In chapter 3, we use scRNA-seq to identify the effects of a novel tuberculosis vaccine strategy. This effort contributes to the goal of identifying correlates of protection against TB infection, a longstanding obstacle in the development of effective TB vaccines. Overall, this body of work contributes to our biological understanding of immunological disease and response to immunomodulatory treatment in the setting of immunosuppressive biologics and immune-stimulating vaccines.