In research driven by insights from human genetics, we use functional genomics to discover and understand the function of important mediators and effectors involved in innate and adaptive immunity.

To this end, we are pursuing integrative systems approaches that closely couple genome-wide experimentation with high-throughput assays, chemical biology, and computational methods. Using these techniques, we are interested in understanding the role of regulatory circuits in mucosal immunity, in particular using (1) insights from human genetics and whole-genome sequencing to understand regulatory mechanisms in innate and adaptive immunity, (2) chemical approaches to controlling cellular disease phenotypes suggested by human genetics, and (3) harnessing computational approaches to uncover both broad and precise patterns of pathway activation in the context of disease and treatment.

One approach to discovering the key mediators of innate and adaptive immunity focuses on defining immune-related genes and placing them in their proper pathways. Current areas of focus using this approach are studies of (1) autophagy (Lassen et al., 2014), (2) host defense and the inflammatory response (Conway et al., 2012), and (3) tolerance and regulatory cells (Khor et al., 2015, recently highlighted in Nature Immunology and selected as an “Editors’ Choice” by Science Translational Medicine).

Using chemical (e.g., small molecule) screening approaches, we can gain insight into disease gene function and place risk genes into signal transduction pathways. Chemical screens have the additional potential to identify small molecule probes and early therapeutic leads, as recently demonstrated by Kuo et al. (paper; press release).

We use the power of computational biology to uncover patterns in complex pathway analysis, as well as to integrate multiple ’omics data types to decipher human disease.