At the core of our research group, we create sequencing technologies to better understand gene regulation across health and disease. In previous work, we have developed Assay for Transpose Accessible Chromatin (ATAC-seq) and have adapted this approach to profile single-cells (scATAC-seq; dsciATAC-seq; SHARE-seq). Advancing beyond single-cell genomics, we now look to build spatial genomics methods to map the organization of genomes within cells (IGS) and tissues (slide-DNA-seq). These tools are designed to be an engine for biological discovery in the lab.

Epigenetic states self-sustain and drift over time. Demonstrating this concept, we have found that genome structure is inherited through cell division and can identify clonal lineage relationships. Inspired by these findings, we seek to broadly understand how epigenetic states are “remembered”, how epigenomic drift may alter cellular function, and look to employ this natural process to trace clonal lineages within tissues.

Changes to the epigenome may “poise” genes for activation to alter lineage outcomes. In our lab we look to measure poised chromatin states in effort to understand how cells modulate their lineage potential over time. To this end we have developed chromatin potential, which predicts lineage choice using poised (open chromatin/no gene expression) chromatin states across single-cell data.

Disease-associated cellular states are key drivers of tissue dysfunction across a broad range of human conditions including aging, autoimmunity, and cancer. We seek to understand their origin, describe how changes to the epigenome poise cell states for new functions, and elucidate their impact in disease. To this end, we engineer disease-like cell states which yields powerful models of disease and provides unique opportunities to develop therapies.

The genetic differences that define us largely occur at non-coding elements altering the function of the epigenome. However, for most human genetic variation we still lack a basic understanding of how and why these genetic differences alter human health and promote disease. In past work, we utilize our expertise in epigenomics to define functional variants in blood development. Moving forward, in collaboration with members at the GRO, we look to build complete functional catalogues of human epigenomes and how they change in response to our environment.

To address these broad questions, we utilize mammalian hematopoiesis as an exemplar model system. Hematopoiesis is an excellent model for uncovering mechanisms underlying adult stem cell fate commitment, wherein a multipotent hematopoietic stem cell (HSC) gives rise to a diverse set of effector immune cells. Over the years, we have extensively studied hematopoietic fates in human and mice using bulk and single-cell tools. Moving forward, we now include animal models and organoid systems, broadening our research scope to new areas of tissue biology.