Unraveling the mysteries of the human immune system through an integrative genomics approach

The immune system impacts almost every category of human disease, including cancer, heart disease, infectious disease, autoimmune disease, and neuropsychiatric disease.  Nonetheless, dysregulation of the immune system in humans is incompletely understood, which limits the development of novel drugs and biomarkers.  We use “humans as the model organism” to understand the role of immune dysregulation in human disease.  In particular, we study the functional consequences of alleles associated with immune-mediated traits, discovered as part of our ongoing genetic studies.  We isolate and perturb immune cells isolated from fresh blood samples drawn from healthy controls or patients with immune-mediated disease, and correlate genotype with functional phenotype (e.g., cell surface protein levels, cytokine secretion, gene expression).  We also use RNAi in primary human cells (and CD4+ T cells in particular) to systematically perturb genes implicated in our genetic studies.  Finally, we use cutting-edge genome-editing techniques such as TALENs, as well as genome-wide expression profiling with RNA-sequencing, to understand systems immunology.

This is an emerging component of our lab, and one that will continue to expand over the next few years.  As more alleles are associated with immune-mediated traits, there will be a growing need to understand the functional consequences of these alleles for drug and biomarker discovery.