Hello! We work on the genetics of immune-mediated and seizure-related diseases at Yale School of Medicine and the Broad Institute of MIT and Harvard. Our main focus is on finding the mechanisms underlying genetic disease. We are also interested in how disease risk variants affect cell biology, what this tells us about the function of cells and how the immune system evolves in humans.
What we do
Over the last few years genetic studies have found hundreds of regions of the human genome which harbor disease risk alleles. These alleles are common in the population and generally contribute a modest amount of risk to carriers. However, in aggregate these variants must influence a limited number of pathways which are presumably involved in disease causation and progress.
We are trying to identify disease-causing pathways by integrating genetics and genomics data. Our activities span the spectrum of generating genetic data, genomic data, through QC and analysis to systems approaches to interpretation.
How we do it
Our overarching model is that genetic risk factors act cumulatively on pathways mediating disease processes. We use genome-wide assays to find suites of interacting genes perturbed by risk alleles and develop models of how this perturbation alters cellular biology and causes disease. Our efforts fall into the following categories:
- Find disease-predisposing alleles using a variety of genetic mapping techniques (association studies, linkage)
- Develop maps of gene interactions in specific cell types using genomic technologies (DNase I hypersensitivity, RNA sequencing, protein-protein interactions etc).
- Develop analytical strategies to integrate genetic and genomic data to discover suites of genes influenced by risk alleles (primarily network and graph theory approaches)
- Develop cell-based models to test whether genetic burden in pathways alters cell biology and how such changes contribute to disease