The immune system is composed of diverse cell types required to defend the host from pathogens and cancer. At the same time, immune cells can overrespond, resulting in autoimmune and inflammatory diseases. Our research aims to improve our understanding of the biology of these diseases, with a focus on the impact of genetics and biological sex on immune cell function. We generate high-resolution transcriptomic and epigenomic maps of immune cells from patients and healthy individuals, and develop techniques to shed light on the molecular mechanisms that drive the pathogenesis of immune-mediated diseases to identify and characterize novel candidate genes for diagnosis and therapeutic targeting.
In genome-wide association studies (GWAS), numerous common genetic variants have been associated with the risk for human disease related to immune cell function/dysfunction, but how these genetic variants affect gene expression and the function of immune cells in health and disease remains largely unknown. The characterization of causal mechanisms that regulate and drive gene expression in specific immune cell types is the key to understand human disease, identify relevant players (involved immune cell types and key candidate genes), develop novel approaches for diagnosis and therapy, and achieve prevention of immune-mediated diseases.
At La Jolla Institute for Immunology, we have established the NIH-funded DICE (Database of Immune Cell Expression, Expression quantitative trait loci [eQTLs] and Epigenomics) project to understand the role of common genetic variants in human disease on a genome-wide level. The generation of high-resolution reference transcriptomic and epigenomic maps of diverse immune cells allows us to identify and characterize causal genetic variants, regulatory mechanisms and novel candidate genes implicated in human disease.
Expanding on these findings, we pursue a translational research program that aims to identify and characterize the functional role of key candidate genes in primary immune cell types as novel targets for therapeutical intervention in immune-mediated diseases. Further, our discovery research program aims to identify causal genetic variants that directly perturb transcription factor (TF) binding and modulate gene expression in immune cells. With this unbiased approach, we are expanding the universe of functional genetic variants in the human genome, and will enhance the understanding of the underlying molecular mechanisms that impact gene expression, chromatin organization and immune cell function, and drive disease susceptibility and pathogenesis.
