Innate and adaptive immunity

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.

Genes and Pathways

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).

Lassen et al.,


Graham et al.,

Nat Commun

Begun et al.,

Cell Rep

Smeekens et al.,

Nat Commun

Huett et al.,

Cell Host Microbe

Conway et al.,


Chemical approaches to controlling cellular disease phenotypes suggested by human genetics

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).

Sundberg et al.,


Kuo et al.,


Aldrich et al.,


Khor et al.,


Shaw et al.,

ACS Chem Bio

Computational biology

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.

Goel et al.,

Nucleic Acids Res

Ng et al.,


Cheng et al.,


Tannahill et al.,


Krishnan et al.,


Doench et al.,

Nat Biotech

Giallourakis et al.,

J Immunol