Genetics and Epigenomics of Immune Function and Autoimmune Disease

Our group aims to understand the genome-wide regulation of human immune cell fate and function and the genetic and epigenetic basis of immune-mediated diseases by leveraging techniques in human genetics, epigenomic profiling, and CRISPR-based screening.

We are working toward understanding the genetic circuits that control human immune cell function in health and disease, including exploring the genetic basis of immune-mediated diseases, both monogenic and complex. We participate in collaborative research aimed at broadly understanding chromatin and gene expression regulation of human primary immune cells, allowing downstream annotation of candidate causal non-coding autoimmunity variants that appear to alter key immune cell cis-regulatory sequences. These systems-scale analyses implicate specific cell types, biological processes, and key non-coding sequences in autoimmunity. 

Our expertise in CRISPR-based perturbations in immune cells allows us to directly test and manipulate the cellular effects of disease-associated variants, coding and non-coding. We have integrated CRISPRa with genome editing in murine models to decode regulatory elements controlling IL2RA, an immune homeostasis gene, gaining functional insights into an autoimmunity risk variant in that locus. Furthermore, we have been able to correct a rare IL2RA mutation in cells from patients with a monogenic autoimmune disease and are advancing this technology toward clinical trial.

Selected Publications

Obesity alters pathology and treatment response in inflammatory disease
Nature, 2022
T cell subset-selective IL2RA enhancers shape autoimmune diabetes risk
bioRxiv, 2020
Landscape of stimulation-responsive chromatin across diverse human immune cells
Nature Genetics, 2019
Discovery of stimulation-responsive immune enhancers with CRISPR activation
Nature, 2017
Genetic and epigenetic fine mapping of causal autoimmune disease variants
Nature, 2015


Media highlights of Alex and the lab’s research.
How Obesity Can Rewire the Immune System and the Response to Immunotherapy—and How to Change That
Obesity can turn a helpful immunotherapy into a harmful one, mouse study shows
In autoimmune diseases affecting millions, researchers pinpoint genetic risks, cellular culprits
Blunting CRISPR’s “scissors” gives new insight into autoimmune disorders
"Gentler” CRISPR sheds light on autoimmune disease