Epigenomics of Disease
Understanding the gene regulatory networks that distinguish healthy versus pathogenic immune responses will inform novel approaches for therapeutic interventions in disease. We integrate global regulatory information from genetic mouse models and primary human samples to identify and characterize the regulators that govern the development, plasticity and pathogenicity of inflammatory immune responses.
- Regulation of functional plasticity in inflammation
- Contribution of non-coding variation to autoimmune disease
- Contribution of non-coding variation to schizophrenia
- Contribution of non-coding variation to rare recessive disorders
Gene Regulation
Genes are used at different levels in different cells and in different people. Those differences in gene levels are often major contributors to disease risk. Understanding how different cells, tissues and individuals set the level at which genes are used remains of the most significant problems in biomedical research today. To address that challenge, we develop and apply new of high-throughput approaches to identify the sequences in the human genome that regulate the use of each gene.
- New high-throughput technologies to quantify regulatory element activity at the genome-scale
- The role of genetic variation in regulatory elements on common and rare disease
- The effects of gene regulatory elements on T cell development and differentiation
Genomics of Drug Response
We are combining state-of-the-art experimental and computational approaches to define how key drugs used in oncology, inflammatory diseases, neurology and genetic diseases impact gene regulation in disease states. The results of these studies will help us better understand and treat disease.
- Genomics of glucocorticoid-mediated gene regulation
- Genomics of response to cancer therapy
Genome Engineering Technologies
Genome engineering technologies like CRISPR, which is used to target, cut, and edit nucleotides (aka gene editing), and alternative systems that can change gene functions by manipulating epigenetic marks and three-dimensional chromatin structure have transformed opportunities to treat human disease. We are working to develop and scale up genome engineering technologies and use these tools in efforts ranging from correcting mutations contributing to genetic disease to systematically uncovering the function of undefined regions of the genome.
- Development of New Genome Engineering Technologies
- Genome Editing To Treat Genetic Disease
- Illuminating the Dark Matter of the Genome
Genome Structure and Function
Approximately 2% of the human genome codes for genes. We know that hidden in the other 98% are gene regulatory element switches that control expression of genes in different cell types, tissues, different genetic backgrounds, stages of development, response to the environment, and in disease. We and others have been identifying the location of these regulatory elements in these different contexts through performing thousands of chromatin accessibility experiments and have identified over 2 million different gene regulatory elements.
- Genome structure comparisons in tissues from genetically diverse mouse strains treated with environmental exposures
- Genome structure comparisons in cultured cells on different matrix densities
- Genome structure changes across primates