William Greenleaf, PhD, Assistant Professor, Departments of Genetics and (by courtesy) of Applied Physics, Stanford University Schools of Medicine and Humanities & Sciences
Research Description: Dr. Greenleaf’s group focuses on understanding “the physical genome” by leveraging high-throughput sequencing to develop a picture of compaction at multiple length scales and over time. It is not hyperbole to say the advances made by Greenleaf and his colleagues are revolutionizing genome biology, significantly impacting the future of medicine. His group has fostered the development of methods that assay open chromatin, nucleosome positions, and transcription factor binding genome-wide in small populations of cells undergoing dynamic processes such as differentiation or stochastic state switching. They are applying these methods to a variety of biological systems including autoimmune diseases and diabetes. They have developed an assay of transposase accessible chromatin (called ATAC-seq) that precisely demarcates regions of the genome that are accessible to the machinery of transcription, and new and efficient methods for genome-wide assay of chromatin looping (called HiChIA). Recently they have also applied this technique to single cells, revealing a rich landscape cis- and trans-acting influencers of regulatory variation. With the H. Chang lab at Stanford, they have provided support to the community of science, and released a number of protocols and analysis standards to enable the application of HiChIA, ATAC-Seq and recent methods called “Hi-ChIP” and “ATAC-see”. They are also developing computational models that link these changes in regulatory state of DNA with changes in gene expression. The Greenleaf community website forum (with >400 members) for ATAC-seq methodology facilitates exchange of protocols and discussion of applications for this popular method. Dr. Greenleaf is highly interactive and a member of a number of consortia, in addition to the SDRC. These include the Stanford Center for Excellence in Genomics (CEGS), a Center for Cooperative Human Immunology (CCHI), and the Genomics of Gene Regulation Consortium (GGR).
Selected relevant publications (Stanford DRC members in BOLD):
1. Buenrostro JD, Wu B, Litzenburger U, Snyder M, Ruff D, Gonzales M, Chang H, Greenleaf, WJ. (2015) “Single-cell chromatin accessibility reveals principles of regulatory variation.” Nature. 523(7561):486-90
2. Buenrostro JD*, Araya C*, Chircus L, Layton C, Snyder M, Chang H, Greenleaf WJ. (2014) “Quantitative, deep mutational profiling for mapping the biophysical and functional evolutionary landscapes of RNA-protein interactions” Nature Biotechnology 32, 562–568.
3. Chen X, Shen Y, Draper W, Buenrostro JD, Litzenburger U, Cho SW, Satpathy AT, Carter AC, Ghosh RP, East-Seletsky A, Doudna JA, Greenleaf WJ, Liphardt JT, Chang HY. ATAC-see reveals the accessible genome by transposase-mediated imaging and sequencing. Nat Methods. 2016 Oct 17. doi: 10.1038/nmeth.4031. [Epub ahead of print]
4. Mumbach MR, Rubin AJ, Flynn RA, Dai C, Khavari PA, Greenleaf WJ, Chang HY. HiChIP: efficient and sensitive analysis of protein-directed genome architecture. Nat Methods. 2016 Nov;13(11):919-922.