William Greenleaf

William Greenleaf, PhD, Associate Professor, Departments of Genetics and (by courtesy) of Applied Physics, Stanford University School of Medicine, and School of 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. Dr. Greenleaf is highly interactive and a member of a number of consortia, in addition to 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. Hilgendorf KI, Johnson CT, Mezger A, Rice SL, Norris AM, Demeter J, Greenleaf WJ, Reiter JF, Kopinke D, Jackson PK. Omega-3 Fatty Acids Activate Ciliary FFAR4 to Control Adipogenesis. Cell. 2019 Nov 27;179(6):1289-1305.e21. doi: 10.1016/j.cell.2019.11.005. PMID: 31761534; PMCID: PMC7332222. 

  2. Satpathy AT, Granja JM, Yost KE, Qi Y, Meschi F, McDermott GP, Olsen BN, Mumbach MR, Pierce SE, Corces MR, Shah P, Bell JC, Jhutty D, Nemec CM, Wang J, Wang L, Yin Y, Giresi PG, Chang ALS, Zheng GXY, Greenleaf WJ, Chang HY. Massively parallel single-cell chromatin landscapes of human immune cell development and intratumoral T cell exhaustion. Nat Biotechnol. 2019 Aug;37(8):925-936. doi: 10.1038/s41587-019-0206-z. PMID: 31375813; PMCID: PMC7299161. 

  3. Arda HE, Tsai J, Rosli YR, Giresi P, Bottino R, Greenleaf WJ, Chang HY, Kim SK. A Chromatin Basis for Cell Lineage and Disease Risk in the Human Pancreas. Cell Syst. 2018 Sep 26;7(3):310-322.e4. doi: 10.1016/j.cels.2018.07.007. PMID: 30145115; PMCID: PMC6347013.