Lenardo/Wherry

Project Title

Molecular mechanisms of inborn errors of immunity in T cells

NIH Mentor

Michael Lenardo

Penn Mentor

E. John Wherry

Project Details

One of the most promising aspects of contemporary immunology is the ability to use advanced genomic and molecular technologies to investigate diseases of the immune system in humans. This is exciting and promising research because it allows us to find immunoregulatory pathways in humans and, at the same time, enables us to diagnose and treat immune diseases with high morbidity and mortality. This project will use genomic technologies and deep profiling of the molecular characteristics of immune cells on a collection of patients with genetic deficiencies in two distinct pathways, T cell receptor signaling and cytokine signaling. By comparing these groups to each other and to normal controls using uniform manifold approximation and projection (UMAP) or other high-dimensional space algorithms, we hope to gain insight on the mechanisms causing altered signaling in these individuals. These techniques may also reveal non-genetic causes in normal subjects, like autoantibodies to cytokines. The interplay between genomic features, gene expression patterns, and external interactions can all serve to provide new insight into antigen and pathogen responses in the healthy and diseased immune system.