William James Greenleaf

William Greenleaf received an A.B. in physics from Harvard University, and received a Gates Fellowship to study computer science for one year at Trinity College in Cambridge, England. After this experience abroad, he returned to Stanford to carry out his Ph.D. in applied physics in the laboratory of Steven Block, where he investigated, at the single-molecule level, the chemo-mechanics of RNA polymerase and the folding of RNA transcripts. He conducted postdoctoral work in the laboratory of Xiaoliang Sunney Xie at Harvard University, where he was awarded a Damon Runyon Cancer Research Foundation Fellowship, and developed new fluorescence-based high-throughput sequencing methodologies. Since moving to Stanford in 2011, he has been named a Baxter Foundation Scholar, as well as a Rita Allen Foundation Scholar. In addition to his position in the Department of Genetics, Greenleaf holds a courtesy appointment in Stanford’s Department Applied Physics. He is a member of Bio-X, the Biophysics Program, the Biomedical Informatics Program and the Cancer Center. He is also a participating member in a number of large genomic consortia (CEGS, GGR).

High-throughput sequencing techniques are revolutionizing biology and promise to have a significant impact on the future of medicine. Greenleaf’s research interests focus on leveraging high-throughput methods to understand “the physical genome” by developing methods to probe both 1) the relationship between DNA sequence and the structure and function of molecules encoded by the genome; as well as 2) the physical compaction and folding of the genome itself, and how this topology influences biological state. 1) His research group is interested in understanding the biophysical basis and evolutionary consequences of sequence-function relationships in biological molecules and their interactions. Toward this goal, they develop ultra-high-throughput methods to quantitatively assay sequence-space in bulk and single-molecule experiments. 2) They also seek to understand the hierarchical folding of genomic DNA into regulated structures, the most basic and important of which is the nucleosome. With this objective in mind, they have developed 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.