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 using high-throughput sequencing and optical microscopy to study gene regulation and chromatin structure. Greenleaf is a co-inventor of ATAC-seq, a widely-used epigenomic method developed in his lab.

Biography

Greenleaf was born and raised in Rochester, Minnesota. He attended Mayo High School and worked as a research assistant at the Mayo Clinic during summers. In 1998, he won 6th place in the Westinghouse Science Talent Search for his project on ultrasound-mediated gene transfection. He graduated with honors from Harvard University in 2002 with a degree in Physics. After that, he studied at Trinity College, University of Cambridge, where he earned a Diploma in Computer Science in 2003. He then started his Ph.D. program in Applied Physics at Stanford University. There, he worked in the laboratory of Steven Block and received funding from the NSF GRFP.

During his Ph.D., Greenleaf was the first or co-first author of articles published in Nature, Science, and Cell. His research focused on single-molecule biophysics. His advisor, Steven Block, called this accomplishment a "perfect trifecta." If including another co-first author publication in Physical Review Letters, it could be called a "quadfecta." Greenleaf received his Ph.D. in Applied Physics from Stanford in January 2008. From 2008 to 2011, he worked on developing new methods for massively parallel sequencing-by-synthesis as a postdoctoral fellow in X. Sunney Xie's lab at Harvard University. In 2011, he returned to Stanford as an assistant professor in the Department of Genetics. He started his own laboratory at the Beckman Center for Molecular and Genetic Medicine. In 2017, Stanford granted him tenure.

Research

During his Ph.D., Greenleaf studied methods to measure forces involved in gene transcription and protein folding using single molecules. With colleagues in the Block lab, he created an optical trapping system that allowed very precise measurements of how RNA polymerase moves along DNA. Using this system, he developed a DNA sequencing method based on the observation that RNA polymerase pauses longer at specific DNA positions when the amount of a particular nucleotide base is limited.

Greenleaf's lab at Stanford has focused on high-throughput sequencing and optical microscopy techniques to study gene regulation and chromatin structure. In 2013, Greenleaf's lab, working with Howard Y. Chang's lab, introduced ATAC-seq, a method to analyze chromatin accessibility across the entire genome. ATAC-seq works by using a special enzyme that moves DNA more efficiently in open chromatin regions. From ATAC-seq data, scientists can identify where nucleosomes and transcription factors are located based on patterns of reduced DNA movement. Since 2019, Greenleaf's lab has partnered with Sergiu P. Pașca's lab to use ATAC-seq to study chromatin changes in human brain organoids.

Other research in Greenleaf's lab has focused on measuring interactions between biomolecules at the single-molecule level. The lab gained attention for modifying Illumina DNA sequencers to study how anti-FLAG antibodies bind to specific proteins, how Argonaute proteins attach to RNA, and how CRISPR-associated proteins interact with DNA. In 2024, Greenleaf's lab published a study in Nature describing models that predict how transcription factors bind to DNA and how these binding patterns influence gene activity.

Biotechnology startups

Greenleaf has worked in many positions at biotech startups. In 2013, Greenleaf helped start Epinomics, a company created from Stanford University, with Chang and two former Stanford students. Epinomics received money from Lightspeed and Founders Fund and was bought by 10x Genomics in 2018. In 2019, Greenleaf helped start Protillion Biosciences, a company that uses proteomics technology developed in his lab. Protillion announced it received money for growth in December 2022, with ARCH Venture Partners and Illumina Ventures leading the effort. As of 2026, Greenleaf worked as a science advisor for 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. He was a Chan Zuckerberg Initiative Fellow from 2017 to 2023 and has been an Arc Institute Innovation Investigator since 2023.

In 2023, Greenleaf was one of eight people chosen to receive the NIH Director's Pioneer Award. This award is given each year to about ten U.S. scientists who have shown great creativity and who develop new methods to solve important problems in biomedical, social science, and behavioral research.