About Our Research

The overall goal in the laboratory is to discover and understand the function of important mediators and effectors involved in innate (autophagy, pathogen-containing vacuole) and adaptive (T cell activation) immunity. Of particular interest are the cellular components and regulatory networks, which interact dynamically within temporal, spatial and patho-physiological contexts of innate immunity. We are pursuing integrative systems approaches that closely couple genome-wide experimentation with high-throughput assays (RNAi and cDNA screens) and computational methods. Using these approaches, we are interested in addressing the following questions:

1. What are the mechanisms by which autophagy regulates innate and adaptive immunity?
2. What are the roles of NOD/LRR domains in sensing microbial effectors?
3. How are innate immune pathways dysregulated in mucosal immunity?

The adaptive immunity program focuses on the elucidation of signal transduction pathways coordinated by the CARMA/Dlg family of scaffold proteins.

Crohn’s disease and ulcerative colitis are debilitating inflammatory diseases of the gastrointestinal tract collectively known as inflammatory bowel diseases. Among complex diseases, genetics has been particularly successful in the identification of genes for IBD with recent efforts in genome-wide association studies bringing the total number of genes to more than 40. These studies have highlighted the significance of the relationship between intracellular responses to microbes and the regulation of adaptive immunity in the pathogenesis of IBD.

With the rapid progress in human genetics it has become clear that a major challenge in the study of complex genetic traits is to determine how disease genes and their corresponding alleles exert their influences on the biology of health and disease. Our lab focuses on applying novel genomic, genetic, and chemical biology approaches to gain insights into the function of genetic variants underlying common inflammatory diseases and to explore the potential for reversing the effects of susceptibility alleles.

Systems biology approaches to understand human disease signaling networks

The discovery of important mediators and effectors involved in immunity requires a deeper exploration of how these function as integrated systems. Especially of interest are the cellular components and regulatory networks which interact dynamically within temporal, spatial and pathophysiological contexts. We are pursuing integrative systems approaches that closely couple genome-wide experimentation with bioinformatics and computational methods.

We hope to gain additional insights about the immune system in terms of the underlying interaction and regulatory networks that define functional modules at the host-pathogen interface. In addition the team of computational biologists and mathematicians in the group are developing testable models using information from genome-wide studies and high-throughput screens to gain insight into molecular mechanisms of autoimmune disorders.