William Greenleaf

William J. Greenleaf (born December 24, 1979) is an American molecular biologist, biophysicist, and inventor who is a professor of genetics at the Stanford University School of Medicine. His research focuses on high-throughput sequencing and optical microscopy methods for studying gene regulation and chromatin structure. Greenleaf is a co-inventor of ATAC-seq, a widely-used epigenomic method developed in his lab.

Biography Greenleaf grew up in Rochester, Minnesota. He attended Mayo High School and worked summers as a research assistant at the Mayo Clinic, winning 6th place in the 1998 Westinghouse Science Talent Search for his project on ultrasound-mediated gene transfection. He graduated cum laude with an A.B. in Physics from Harvard University in 2002, followed by a stint as a Gates Cambridge Scholar at Trinity College, University of Cambridge, from which he received a Dip. Comp. Sci. in 2003. Greenleaf then entered the Applied Physics Ph.D. program at Stanford University, where he joined the laboratory of Steven Block and was funded by the NSF GRFP.

Greenleaf was first or co-first author of publications in Nature, Science, and Cell resulting from his Ph.D. work on single-molecule biophysics, an achievement his advisor Block called a "perfect trifecta," or "quadfecta" if one were to include Greenleaf's additional co-first author publication in Physical Review Letters. Greenleaf received his Ph.D. in Applied Physics from Stanford in January 2008. Using this system, he developed a method for DNA sequencing based on the observation that, when the concentration of a given nucleotide base is limiting, RNA polymerase pauses for longer amounts of time at sequence positions corresponding to that base.

Greenleaf's lab at Stanford has focused on high-throughput sequencing and optical microscopy methods for studying gene regulation and chromatin structure.

Other work in Greenleaf's lab has centered on single-molecule measurements of biomacromolecular interactions. The lab attracted attention for disassembling and repurposing Illumina DNA sequencers, an effort that enabled large-scale analyses of FLAG epitope binding by anti-FLAG antibodies, target RNA binding by Argonaute proteins, and target DNA binding by CRISPR-associated proteins. In 2024, Greenleaf's lab published a study in Nature describing the development of thermodynamic and kinetic models to quantitatively predict transcription factor binding microstates and relate those microstates to gene expression.

Biotechnology startups Greenleaf has held several roles with biotech startups. In 2013, Greenleaf co-founded Epinomics, a Stanford biotech spinout, with Chang and two former Stanford students. Epinomics raised venture capital from Lightspeed and Founders Fund and was acquired by 10x Genomics in 2018. In 2019, Greenleaf co-founded Protillion Biosciences, a spinout commercializing proteomics technology developed in his lab. Protillion announced its Series A fundraise, led by ARCH Venture Partners and Illumina Ventures, in December 2022. As of 2026, Greenleaf served as a scientific advisor to Guardant Health and Ultima Genomics.

Awards and recognition Greenleaf was named an ARCS Scholar in 2006, a Damon Runyon Fellow in 2009, a Rita Allen Scholar in 2011, a Baxter Foundation Faculty Fellow in 2014, and the E. Bright Wilson Prize winner in 2017.

Greenleaf was one of eight recipients of the 2023 NIH Director's Pioneer Award, presented annually to approximately ten U.S. scientists with "outstanding records of creativity" who "develop pioneering approaches to major challenges in biomedical, social science, and behavioral research."