In every single cell in the human body, the six feet of DNA is compacted in the micrometer space of the nucleus by wrapping around spools called nucleosomes in addition to extraordinary three-dimensional folding of DNA inside the nucleus. Tissue-specific decoding of the genetic information from this extreme compression is orchestrated by specialized proteins capable of binding DNA in a sequence-specific manner. Locally, a number of proteins called lineage-determining transcription factors can access their binding sites even if they are partially occluded by nucleosomes, recruiting chromatin-remodeling enzymes and exposing the underlying DNA. Globally, sequence-specific proteins such as CTCF act as structural regulators of spatial genome organization. Considering that every two human genomes contain more than 6 million nucleotide differences and the fact that genetics is a major determinant of susceptibility to common diseases, it is essential to understand how the packaging of DNA inside the nucleus becomes resilient or susceptible to diseases due to large numbers of sequence variation. The overarching goal of the Vahedi laboratory is to understand the molecular mechanisms through which genomic information in our immune cells is interpreted in normal development and further dissect how common genetic variation can lead to misinterpretation of the genetic material in immune mediated diseases, particularly autoimmune disorders.

The multidisciplinary nature of our laboratory allows us to exploit computational and cutting-edge experimental approaches and generate unbiased maps of genome organization in primary immune cells in humans and mice. We further follow our hypothesis-generating yet unbiased efforts with experiments dissecting the mechanisms of our predictions using genome editing in mice or cell lines which provides us with an unparalleled opportunity to rigorously define the link between genetics and chromatin organization.